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What do high BUN/Cr ratios mean?
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
He has been in good health with the only medical problem in his history being depression.
He is taking sertraline. On exam, his blood pressure is 100/60, and his pulse is 100, both while lying down. His blood pressure while standing is 90/60 and his pulse while standing is 130. The rest of his exam is normal. His lab values include hemoglobin of 10, hematocrit of 30, white blood cell of 4.6, platelet count of 175,000, sodium of 142, chloride of 100, bicarbonate of 24, potassium of 3.8, blood urea nitrogen (BUN) of 38, and creatinine clearance (Cr) of 1.1.
What is the most likely source of his bleeding?
A. Gastric ulcer
B. Meckel’s diverticulum
C. Arteriovenous malformation
D. Diverticulosis
E. Hemorrhoids
What makes the most sense
The most likely cause of this patient’s maroon stool is an upper gastrointestinal bleed, so it would make the most sense for a gastric ulcer to be the source of his bleeding. The clue here is the very high BUN/Cr ratio.
We were all taught early in our training that a high BUN/Cr ratio represented volume depletion. This is certainly the most common cause, but very high BUN/Cr ratios (over 30) can represent causes beyond volume depletion.
Witting and colleagues studied factors that predicted upper GI bleeding in patients presenting without hematemesis. They found that the three strongest predictors were black stool (odds ratio, 16.6), BUN/Cr ratio greater than 30 (OR, 10), and age greater than 50 (OR, 8.4).1
Srygley and colleagues reviewed high-quality studies of factors associated with upper GI bleeding.2 Factors that were found to increase the likelihood of an upper gastrointestinal bleed were Melenic stool on exam (likelihood ratio, 25), blood or coffee grounds on nasogastric aspiration (LR, 9.6), and BUN/Cr ratio greater than 30 (LR, 7.5).
Very high BUN/Cr ratios can indicate problems other than UGI bleeding and volume depletion. High BUN/Cr ratios are seen in patients with heart failure.
Zhang and colleagues studied if a high BUN/Cr ratio helped distinguish heart failure from asthma and chronic obstructive pulmonary disease (COPD).3 They found that, compared with those in the asthma group, the BUN/Cr ratios were significantly increased in the heart failure group (P < .05), whereas no significant differences in BUN/Cr ratios were found between the asthma and COPD groups.
Cheang and colleagues conducted their own study, as well as a meta-analysis, looking to see if high BUN/Cr ratios predicted increased mortality in patients with acute heart failure.4 In the meta-analysis of 8 studies (including their own), they found that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (hazard ratio, 1.77; 95% confidence interval, 1.52-2.07).
High dose corticosteroids can raise BUN levels, especially in patients with chronic kidney disease, and cause unexpectedly high BUN/Cr ratios.
Pearl
Very high BUN/Cr ratios (greater than 30) can signify upper GI bleeding, heart failure, or high-dose corticosteroid use.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Am J Emerg Med. 2006 May;24(3):280-5.
2. JAMA. 2012;307(10):1072-9.
3. Comput Math Methods Med. 2022 Jul 21. doi: 10.1155/2022/4586458.
4. Cardiorenal Med. 2020;10:415-28.
Experts share real-world experience prescribing voclosporin, belimumab for lupus nephritis
Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.
Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.
How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.
Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.
Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
Lack of real-world data
The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.
“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.
“It’s too soon for any appreciable data to be collected.”
Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.
“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.
Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.
“Most community-based rheumatologists such as myself are too busy,” he said. “Why we are not getting case series from major medical centers, I am not sure.”
When this news organization asked GlaxoSmithKline (GSK) if the company tracked data on real-world use of belimumab, a spokesperson responded that the drug “has extensive clinical efficacy and safety data, and 12 years of postapproval experience, demonstrating its efficacy in SLE to reduce disease activity in multiple organ systems, reduce severe flares, and enabling some patients to taper steroid use over time.”
The spokesperson also referenced published data where belimumab “showed improvement in lupus nephritis when compared to standard therapy alone,” and that the drug “has an established safety profile that has shown to be consistent in diverse patient populations across multiple clinical trials.”
Aurinia Pharmaceuticals did not respond when sent an inquiry on whether the company tracked similar real-world data on voclosporin use.
Prescribing experience
Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.
“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.
“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.
Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.
However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.
Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.
One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.
“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”
While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.
“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.
The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.
Treatment preference
A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.
Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.
Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”
For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.
Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.
Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.
“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.
With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.
How patients are responding
Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.
For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.
Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.
“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.
Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.
Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.
Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.
Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.
Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.
Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.
How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.
Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.
Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
Lack of real-world data
The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.
“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.
“It’s too soon for any appreciable data to be collected.”
Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.
“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.
Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.
“Most community-based rheumatologists such as myself are too busy,” he said. “Why we are not getting case series from major medical centers, I am not sure.”
When this news organization asked GlaxoSmithKline (GSK) if the company tracked data on real-world use of belimumab, a spokesperson responded that the drug “has extensive clinical efficacy and safety data, and 12 years of postapproval experience, demonstrating its efficacy in SLE to reduce disease activity in multiple organ systems, reduce severe flares, and enabling some patients to taper steroid use over time.”
The spokesperson also referenced published data where belimumab “showed improvement in lupus nephritis when compared to standard therapy alone,” and that the drug “has an established safety profile that has shown to be consistent in diverse patient populations across multiple clinical trials.”
Aurinia Pharmaceuticals did not respond when sent an inquiry on whether the company tracked similar real-world data on voclosporin use.
Prescribing experience
Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.
“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.
“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.
Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.
However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.
Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.
One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.
“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”
While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.
“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.
The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.
Treatment preference
A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.
Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.
Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”
For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.
Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.
Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.
“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.
With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.
How patients are responding
Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.
For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.
Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.
“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.
Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.
Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.
Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.
Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.
Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.
Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.
How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.
Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.
Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
Lack of real-world data
The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.
“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.
“It’s too soon for any appreciable data to be collected.”
Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.
“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.
Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.
“Most community-based rheumatologists such as myself are too busy,” he said. “Why we are not getting case series from major medical centers, I am not sure.”
When this news organization asked GlaxoSmithKline (GSK) if the company tracked data on real-world use of belimumab, a spokesperson responded that the drug “has extensive clinical efficacy and safety data, and 12 years of postapproval experience, demonstrating its efficacy in SLE to reduce disease activity in multiple organ systems, reduce severe flares, and enabling some patients to taper steroid use over time.”
The spokesperson also referenced published data where belimumab “showed improvement in lupus nephritis when compared to standard therapy alone,” and that the drug “has an established safety profile that has shown to be consistent in diverse patient populations across multiple clinical trials.”
Aurinia Pharmaceuticals did not respond when sent an inquiry on whether the company tracked similar real-world data on voclosporin use.
Prescribing experience
Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.
“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.
“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.
Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.
However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.
Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.
One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.
“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”
While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.
“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.
The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.
Treatment preference
A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.
Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.
Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”
For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.
Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.
Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.
“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.
With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.
How patients are responding
Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.
For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.
Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.
“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.
Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.
Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.
Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.
Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.
Postpartum urinary retention: Intermittent catheterization may be best
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
Intermittent catheterization every 6 hours in postpartum women with urinary retention may be a better strategy than extended catheterization over 24 hours, a new prospective, randomized, controlled study suggests.
Patients who were catheterized every 6 hours took significantly less time to reach full relief than those who were catheterized for at least 24 hours (mean 10.2 ± 11.8 hours vs. 26.5 ± 9.0 hours, P < .001, respectively), Israeli researchers found. Their research was released at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.
“There was no difference in hospital stay or in the rate of positive urine culture after catheter removal,” said ob.gyn. Dana Vitner, MD, of Rambam Health Care Campus in Haifa, Israel, in a presentation at the conference. “Our conclusion is that intermittent catheterization for postpartum urinary retention results in shorter time to resolution with a higher satisfaction rate and no additional complications.”
The true incidence of postpartum urinary retention is unclear, and estimates vary widely, said ob.gyn. and surgeon Lisa Hickman, MD, of the Ohio State University, Columbus, in an interview. “This is likely because many cases of covert urinary retention – when postpartum women are able to urinate but have incomplete emptying – go undiagnosed unless you are screening for it.”
According to Dr. Hickman, risk factors for postpartum urinary retention include operative vaginal births, having an epidural, obstetric anal sphincter injury, episiotomy, large newborns, first-time births, and prolonged induction of labor. Most cases resolve within 72 hours, she said, but they can lead to rare complications such as bladder injury.
For the new study, researchers defined urinary retention at the bladder holding least 150 mL more than 6 hours after vaginal delivery or removal of an in-dwelling catheter after cesarean delivery. “The treatment is catheterization,” Dr. Vitner said. “However, there is no standard protocol.”
From 2020 to 2022, researchers randomly assigned 73 women to the intermittent catheterization group and 74 to continuous catheterization. The average ages in the groups were 27.7 and 29.1 years, respectively (P = .11) and other characteristics such as body mass index, parity, infant birth weight, and mode of delivery were similar.
Most women in the intermittent catheterization group needed just one catheterization to reach resolution (75.3%); 93.2% had resolution after two, and 95.9% reached it after three. All resolved their urinary retention by 48 hours.
In the continuous catheterization group, 90.5% reached resolution at 24 hours, 97.3% at 48 hours, and 100% at 72 hours. Birth satisfaction scores were higher in the intermittent catheterization group (P < .001).
Dr. Hickman, who did not take part in the study, said the findings are helpful. Randomized, controlled trials are “important to get a better understanding of the natural history of this condition and ways to improve how we manage it clinically,” she said. Should intermittent catheterization become routine? “You need to have the staffing and the resources in order to do that, such as a bladder scanner and intermittent catheterization supplies,” Dr. Hickman said. “It can be time-intensive to continue to follow the patients to make sure they are voiding normally. And there may be many hospitals in the country that just don’t have the resources to do this, especially with all the current workforce issues.”
She added that some patients may not want the intermittent approach: “It can be uncomfortable for patients. They’ve just delivered a baby, they are likely experiencing discomfort from their delivery, and their anatomy can be distorted,” she said. “Some patients may say, ‘I would prefer you not insert a catheter into my bladder every few hours.’ They may just want to rest after having a baby.”
The best approach is to let patients make an informed choice, Dr. Hickman said. She recommended that clinicians say something like, “Because of your delivery, you are not able to empty your bladder all the way. This is typically a self-limited problem, meaning that it will likely resolve within a few days. But in the meantime, we need to let your bladder rest so that it can have time to start functioning on its own.” And then, she said, explain the catheterization options.
Dr. Vitner and Dr. Hickman have no disclosures.
FROM THE PREGNANCY MEETING
Two biomarkers identify high-risk lupus nephritis
Levels at the time of flare predict outcomes
At the time of a nephritis flare in patients with systemic lupus erythematosus (SLE), elevated levels of two neutrophil extracellular trap (NET) protein complexes, elastase-DNA and HMGB1-DNA, predict declining renal function, poor response to therapy, and adverse renal outcomes, according to work presented at the annual meeting of the Canadian Rheumatology Association.
“These proteins are not only predominantly elevated in patients with proliferative lupus nephritis, but they correlate with adverse renal outcomes when patients are followed over 24 months,” reported Laura P. Whittall-Garcia, MD, a clinical fellow in rheumatology at the University of Toronto.
Lupus nephritis is common in SLE, developing in about 50% of patients, according to Dr. Whittall-Garcia. Of these, up to 20% will not respond to standard therapies, typically resulting in end-stage renal disease. Up until now, there has been no reliable method of predicting this adverse clinical course.
Proteins identified in NETs
The series of studies conducted by Dr. Whittall-Garcia and coinvestigators were focused on NETs, a network of strings of DNA that typically bind pathogenic microbes to prevent infection but can participate in the pathology of immune-mediated conditions. As Dr. Whittall-Garcia explained, DNA extruded from NETs has been a source of autoantigens.
Based on earlier work, they pursued the hypothesis that high mobility group box 1 (HMGB1) and elastase, which are both NET components, mediate NETosis, the immune response that protects against microbes in healthy individuals but contributes to tissue damage in patients with immune-related disorders. The first aim of this work was to confirm that elevations of elastase-DNA and HMGB1-DNA correlate with active lupus nephritis. The second aim was to determine if levels of these proteins at the time of lupus nephritis flare predicted renal outcomes at 12 and 24 months.
To pursue the first hypothesis, 49 patients with active SLE (18 of whom had active lupus nephritis) were evaluated along with 23 patients with inactive SLE and 20 healthy controls.
Highest levels seen in proliferative nephritis
Relative to healthy controls, patients with active SLE have highly significantly increased levels of both proteins (P < .0001). And relative to those with inactive SLE, the levels of active patients were higher but fell short of statistical significance. However, when the researchers compared those with active lupus nephritis with those who had active SLE but no nephritis, both proteins were significantly higher (P < .04), and the levels in patients with proliferative relative to nonproliferative lupus nephritis were higher still (P < .009).
To pursue the second aim of the study, the researchers retrospectively evaluated 109 patients with SLE. All had active lupus nephritis, a baseline estimated glomerular filtration rate (eGFR) greater than 30 mL/min prior to the flare, and at least 2 years of follow-up. They evaluated complete response at 12 and 24 months, percent decline in eGFR, and severe renal impairment (eGFR ≤ 30 mL/min) in the context of levels of elastase and HMGB1.
With elevations in either NET remnant, the odds ratio of failing to achieve a complete response at 24 months were approximately doubled for elastase-DNA (OR, 1.96; P = .01) and for HMGB1 (OR, 2.61; P = .02). For the endpoint of severe renal impairment 24 months after a lupus nephritis flare, there was also a positive association with both elastase-DNA (OR, 1.55; P = .005) and HMBG1-DNA (OR, 1.91; P = .01).
“For every 100-unit increase in elastase-DNA complexes, there is a 4.8% decrease in eGFR,” reported Dr. Whittall-Garcia, who noted this relationship was highly statistically significant (P < .0001). For HMGB1-DNA, each 100-unit increase was associated with a 5.3% decrease in eGFR (P = .0006).
No other biomarkers compare for prognosis
“After adjusting for multiple variables, these protein levels at the time of the flare outperformed all conventional biomarkers, including proteinuria and complement levels,” Dr. Whittall-Garcia said.
Larger validating studies are needed, but Dr. Whittall-Garcia is optimistic that measuring these NET remnant levels will prove useful for monitoring patients at the time of the lupus nephritis flare and over time for the purposes of predicting adverse outcomes and response to therapy.
Although more work is needed, Adegbenga A. Bankole, MD, associate professor of medicine at Virginia Tech University and chief of the rheumatology division at the Carilion Clinic, both in Roanoke, agreed that this is a promising research direction. He reported that NETs have been attracting interest at several research centers for their potential in helping to understand the pathogenesis of lupus nephritis.
“It is unlikely that any one test will ever be a panacea in the diagnosis or predictor of outcomes in lupus nephritis,” Dr. Bankole said in an interview, but “given the importance of NETosis in the development of this disease, studies like this will form the basis of the multistep process through which we will improve patient care.”
With further progress in this area, Dr. Bankole predicted that these studies will lead to clinical applications.
“Dr. Whittall-Garcia and her team will help in the development of diagnostic and/or predictive algorithms that may go on to help improve survival of future patients with SLE,” he said.Dr. Whittall-Garcia and Dr. Bankole report they have no relevant financial relationships.
Levels at the time of flare predict outcomes
Levels at the time of flare predict outcomes
At the time of a nephritis flare in patients with systemic lupus erythematosus (SLE), elevated levels of two neutrophil extracellular trap (NET) protein complexes, elastase-DNA and HMGB1-DNA, predict declining renal function, poor response to therapy, and adverse renal outcomes, according to work presented at the annual meeting of the Canadian Rheumatology Association.
“These proteins are not only predominantly elevated in patients with proliferative lupus nephritis, but they correlate with adverse renal outcomes when patients are followed over 24 months,” reported Laura P. Whittall-Garcia, MD, a clinical fellow in rheumatology at the University of Toronto.
Lupus nephritis is common in SLE, developing in about 50% of patients, according to Dr. Whittall-Garcia. Of these, up to 20% will not respond to standard therapies, typically resulting in end-stage renal disease. Up until now, there has been no reliable method of predicting this adverse clinical course.
Proteins identified in NETs
The series of studies conducted by Dr. Whittall-Garcia and coinvestigators were focused on NETs, a network of strings of DNA that typically bind pathogenic microbes to prevent infection but can participate in the pathology of immune-mediated conditions. As Dr. Whittall-Garcia explained, DNA extruded from NETs has been a source of autoantigens.
Based on earlier work, they pursued the hypothesis that high mobility group box 1 (HMGB1) and elastase, which are both NET components, mediate NETosis, the immune response that protects against microbes in healthy individuals but contributes to tissue damage in patients with immune-related disorders. The first aim of this work was to confirm that elevations of elastase-DNA and HMGB1-DNA correlate with active lupus nephritis. The second aim was to determine if levels of these proteins at the time of lupus nephritis flare predicted renal outcomes at 12 and 24 months.
To pursue the first hypothesis, 49 patients with active SLE (18 of whom had active lupus nephritis) were evaluated along with 23 patients with inactive SLE and 20 healthy controls.
Highest levels seen in proliferative nephritis
Relative to healthy controls, patients with active SLE have highly significantly increased levels of both proteins (P < .0001). And relative to those with inactive SLE, the levels of active patients were higher but fell short of statistical significance. However, when the researchers compared those with active lupus nephritis with those who had active SLE but no nephritis, both proteins were significantly higher (P < .04), and the levels in patients with proliferative relative to nonproliferative lupus nephritis were higher still (P < .009).
To pursue the second aim of the study, the researchers retrospectively evaluated 109 patients with SLE. All had active lupus nephritis, a baseline estimated glomerular filtration rate (eGFR) greater than 30 mL/min prior to the flare, and at least 2 years of follow-up. They evaluated complete response at 12 and 24 months, percent decline in eGFR, and severe renal impairment (eGFR ≤ 30 mL/min) in the context of levels of elastase and HMGB1.
With elevations in either NET remnant, the odds ratio of failing to achieve a complete response at 24 months were approximately doubled for elastase-DNA (OR, 1.96; P = .01) and for HMGB1 (OR, 2.61; P = .02). For the endpoint of severe renal impairment 24 months after a lupus nephritis flare, there was also a positive association with both elastase-DNA (OR, 1.55; P = .005) and HMBG1-DNA (OR, 1.91; P = .01).
“For every 100-unit increase in elastase-DNA complexes, there is a 4.8% decrease in eGFR,” reported Dr. Whittall-Garcia, who noted this relationship was highly statistically significant (P < .0001). For HMGB1-DNA, each 100-unit increase was associated with a 5.3% decrease in eGFR (P = .0006).
No other biomarkers compare for prognosis
“After adjusting for multiple variables, these protein levels at the time of the flare outperformed all conventional biomarkers, including proteinuria and complement levels,” Dr. Whittall-Garcia said.
Larger validating studies are needed, but Dr. Whittall-Garcia is optimistic that measuring these NET remnant levels will prove useful for monitoring patients at the time of the lupus nephritis flare and over time for the purposes of predicting adverse outcomes and response to therapy.
Although more work is needed, Adegbenga A. Bankole, MD, associate professor of medicine at Virginia Tech University and chief of the rheumatology division at the Carilion Clinic, both in Roanoke, agreed that this is a promising research direction. He reported that NETs have been attracting interest at several research centers for their potential in helping to understand the pathogenesis of lupus nephritis.
“It is unlikely that any one test will ever be a panacea in the diagnosis or predictor of outcomes in lupus nephritis,” Dr. Bankole said in an interview, but “given the importance of NETosis in the development of this disease, studies like this will form the basis of the multistep process through which we will improve patient care.”
With further progress in this area, Dr. Bankole predicted that these studies will lead to clinical applications.
“Dr. Whittall-Garcia and her team will help in the development of diagnostic and/or predictive algorithms that may go on to help improve survival of future patients with SLE,” he said.Dr. Whittall-Garcia and Dr. Bankole report they have no relevant financial relationships.
At the time of a nephritis flare in patients with systemic lupus erythematosus (SLE), elevated levels of two neutrophil extracellular trap (NET) protein complexes, elastase-DNA and HMGB1-DNA, predict declining renal function, poor response to therapy, and adverse renal outcomes, according to work presented at the annual meeting of the Canadian Rheumatology Association.
“These proteins are not only predominantly elevated in patients with proliferative lupus nephritis, but they correlate with adverse renal outcomes when patients are followed over 24 months,” reported Laura P. Whittall-Garcia, MD, a clinical fellow in rheumatology at the University of Toronto.
Lupus nephritis is common in SLE, developing in about 50% of patients, according to Dr. Whittall-Garcia. Of these, up to 20% will not respond to standard therapies, typically resulting in end-stage renal disease. Up until now, there has been no reliable method of predicting this adverse clinical course.
Proteins identified in NETs
The series of studies conducted by Dr. Whittall-Garcia and coinvestigators were focused on NETs, a network of strings of DNA that typically bind pathogenic microbes to prevent infection but can participate in the pathology of immune-mediated conditions. As Dr. Whittall-Garcia explained, DNA extruded from NETs has been a source of autoantigens.
Based on earlier work, they pursued the hypothesis that high mobility group box 1 (HMGB1) and elastase, which are both NET components, mediate NETosis, the immune response that protects against microbes in healthy individuals but contributes to tissue damage in patients with immune-related disorders. The first aim of this work was to confirm that elevations of elastase-DNA and HMGB1-DNA correlate with active lupus nephritis. The second aim was to determine if levels of these proteins at the time of lupus nephritis flare predicted renal outcomes at 12 and 24 months.
To pursue the first hypothesis, 49 patients with active SLE (18 of whom had active lupus nephritis) were evaluated along with 23 patients with inactive SLE and 20 healthy controls.
Highest levels seen in proliferative nephritis
Relative to healthy controls, patients with active SLE have highly significantly increased levels of both proteins (P < .0001). And relative to those with inactive SLE, the levels of active patients were higher but fell short of statistical significance. However, when the researchers compared those with active lupus nephritis with those who had active SLE but no nephritis, both proteins were significantly higher (P < .04), and the levels in patients with proliferative relative to nonproliferative lupus nephritis were higher still (P < .009).
To pursue the second aim of the study, the researchers retrospectively evaluated 109 patients with SLE. All had active lupus nephritis, a baseline estimated glomerular filtration rate (eGFR) greater than 30 mL/min prior to the flare, and at least 2 years of follow-up. They evaluated complete response at 12 and 24 months, percent decline in eGFR, and severe renal impairment (eGFR ≤ 30 mL/min) in the context of levels of elastase and HMGB1.
With elevations in either NET remnant, the odds ratio of failing to achieve a complete response at 24 months were approximately doubled for elastase-DNA (OR, 1.96; P = .01) and for HMGB1 (OR, 2.61; P = .02). For the endpoint of severe renal impairment 24 months after a lupus nephritis flare, there was also a positive association with both elastase-DNA (OR, 1.55; P = .005) and HMBG1-DNA (OR, 1.91; P = .01).
“For every 100-unit increase in elastase-DNA complexes, there is a 4.8% decrease in eGFR,” reported Dr. Whittall-Garcia, who noted this relationship was highly statistically significant (P < .0001). For HMGB1-DNA, each 100-unit increase was associated with a 5.3% decrease in eGFR (P = .0006).
No other biomarkers compare for prognosis
“After adjusting for multiple variables, these protein levels at the time of the flare outperformed all conventional biomarkers, including proteinuria and complement levels,” Dr. Whittall-Garcia said.
Larger validating studies are needed, but Dr. Whittall-Garcia is optimistic that measuring these NET remnant levels will prove useful for monitoring patients at the time of the lupus nephritis flare and over time for the purposes of predicting adverse outcomes and response to therapy.
Although more work is needed, Adegbenga A. Bankole, MD, associate professor of medicine at Virginia Tech University and chief of the rheumatology division at the Carilion Clinic, both in Roanoke, agreed that this is a promising research direction. He reported that NETs have been attracting interest at several research centers for their potential in helping to understand the pathogenesis of lupus nephritis.
“It is unlikely that any one test will ever be a panacea in the diagnosis or predictor of outcomes in lupus nephritis,” Dr. Bankole said in an interview, but “given the importance of NETosis in the development of this disease, studies like this will form the basis of the multistep process through which we will improve patient care.”
With further progress in this area, Dr. Bankole predicted that these studies will lead to clinical applications.
“Dr. Whittall-Garcia and her team will help in the development of diagnostic and/or predictive algorithms that may go on to help improve survival of future patients with SLE,” he said.Dr. Whittall-Garcia and Dr. Bankole report they have no relevant financial relationships.
FROM CRA 2023
Fair access crucial for new diabetes/kidney disease drugs, say guidelines
The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.
But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.
The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.
The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.
The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.
“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
Generics to the rescue
One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.
That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.
Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.
However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.
The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.
Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
Incentivize formulary listings
Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.
The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.
“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.
Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.
But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.
The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.
The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.
The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.
“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
Generics to the rescue
One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.
That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.
Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.
However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.
The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.
Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
Incentivize formulary listings
Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.
The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.
“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.
Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The 2022 guideline update released by the KDIGO organization for managing people with diabetes and chronic kidney disease (CKD) highlighted the safety and expanded, evidence-based role for agents from three drug classes: the SGLT2 inhibitors, the GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonists.
But this key take-away from the guideline also underscored the challenges for ensuring fair and affordable access among US patients to these practice-changing medications.
The impact of widespread adoption of these three drug classes into routine US management of people with diabetes and CKD “will be determined by how effective the health care system and its patients and clinicians are at overcoming individual and structural barriers,” write Milda Saunders, MD, and Neda Laiteerapong, MD, in an editorial that accompanied the publication of a synopsis of the 2022 guideline update in Annals of Internal Medicine.
The synopsis is an 11-page distillation of the full 128-page guideline released by the Kidney Disease: Improving Global Outcomes (KDIGO) organization in 2022.
The recommendations in the 2022 guideline update “are exciting for their potential to change the natural history of CKD and diabetes, but their effect could be highly limited by barriers at multiple levels,” write Dr. Saunders and Dr. Laiteerapong, two internal medicine physicians at the University of Chicago.
“Without equitable implementation of the KDIGO 2022 guidelines there is a potential that clinical practice variation will increase and widen health inequities for minoritized people with CKD and diabetes,” they warn.
Generics to the rescue
One potentially effective, and likely imminent, way to level the prescribing field for patients with CKD and diabetes is for agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor, glucagonlike peptide-1 (GLP-1) receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes to become available in generic formulations.
That should lower prices and thereby boost wider access and will likely occur fairly soon for at least two of the three drug classes, Dr. Laiteerapong predicts.
Some GLP-1 receptor agonists have already escaped patent exclusivity or will do so in 2023, she notes, including the anticipated ability of one drugmaker to start U.S. marketing of generic liraglutide by the end of 2023.
However, whether that manufacturer, Teva, proceeds with generic liraglutide “is a big question,” Dr. Laiteerapong said in an interview. She cited Teva’s history of failing to introduce a generic formulation of exenatide onto the U.S. market even though it has had a green light to do so since 2017.
The only nonsteroidal mineralocorticoid receptor antagonist now on the market is finerenone (Kerendia), which will not go off patent for several more years, but for some branded SGLT2 inhibitors, U.S. patents will expire in 2025. In addition, remogliflozin is an SGLT2 inhibitor that “may have already lost patent exclusivity,” noted Dr. Laiteerapong, although it has also never received U.S. marketing approval.
Dr. Laiteerapong expressed optimism that the overall trajectory of access is on the rise. “Many people have type 2 diabetes, and these drugs are in demand,” she noted. She also pointed to progress recently made on insulin affordability. “Things will get better as long as people advocate and argue for equity,” she maintained.
Incentivize formulary listings
Dr. Laiteerapong cited other approaches that could boost access to these medications, such as “creating incentives for pharmaceutical companies to ensure that [these drugs] are on formularies” of large, government-affiliated U.S. health insurance programs, such as Medicare Advantage plans, Medicare Part D, state Medicaid plans, and coverage through U.S. Veterans Affairs and the Tricare health insurance plans available to active members of the US military.
The editorial she coauthored with Dr. Saunders also calls for future collaborations among various medical societies to create “a more unified and streamlined set of recommendations” that benefits patients with diabetes, CKD, and multiple other chronic conditions.
“Over the last decade, we have seen more societies willing to present cooperative guidelines, as well as a surge in research on patients who live with multiple chronic conditions. There is momentum that will allow these different societies to work together,” Dr. Laiteerapong said.
Dr. Laiteerapong and Dr. Saunders have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Dapagliflozin reduces hospitalizations in patients with CKD
These findings add to a growing body of evidence supporting a range of positive benefits from dapagliflozin, including reduced risks of mortality, cardiovascular events, and kidney events, lead author Meir Schechter, MD, PhD, of the Hebrew University of Jerusalem and colleagues wrote in Annals of Internal Medicine.“Although cardiovascular and kidney outcomes with SGLT2 inhibitors have been studied extensively, there is a paucity of data evaluating the effects of SGLT2 inhibitors on hospitalizations for any cause.”
The findings are based on a post hoc analysis of the DAPA-CKD trial, which involved 4,304 patients with CKD in 21 countries. Patients were randomized in a 1:1 ratio to receive dapagliflozin 10 mg orally once a day or matching placebo. The present analysis quantified first hospitalizations for any cause, all hospitalizations, cause-specific hospitalizations, and several related outcomes.
After a median follow-up of 2.4 years, 28% of the population had been hospitalized a total of 2,072 times.
Compared with placebo, dapagliflozin significantly reduced risk of first hospitalization by 16% (hazard ratio, 0.84; 95% confidence interval, 0.75-0.94) and rate of all hospitalizations by 21% (rate ratio, 0.79; 95% CI, 0.70-0.89). These findings remained significant regardless of type 2 diabetes status, with significant benefits seen across reasons for admission, including renal/urinary disorders, cardiac disorders, neoplasms, and metabolism/nutrition disorders. In addition, dapagliflozin was associated with shorter mean time in hospital (2.3 vs. 2.8 days; P = .027) and longer time alive and out of hospital (354.9 vs. 351.7; P = .023).
“These findings highlight additional benefits of dapagliflozin beyond those seen for cardiovascular and kidney events, all-cause and cause-specific mortality, eGFR [estimated glomerular filtration rate] slope, and albuminuria and should be considered when evaluating the totality of evidence favoring provision of dapagliflozin to patients with CKD,” the investigators concluded.
Positive data, positive experiences
Shree Mulay, MD, a nephrologist in private practice in western Tennessee, said this study is “one of several other articles that already exist” demonstrating the broad benefits of SGLT2 inhibitors.
“The evidence is pretty substantial,” Dr. Mulay said in an interview. “I think SGLT2 inhibitors are the new statin of this era. ... I won’t be surprised if in the next year or 2 or 3 they truly become the standard of care.”
Dr. Mulay also speaks from experience working in both the chronic and acute setting, where he’s observed “some magical stuff happening” in patients started on SGLT2 inhibitors, especially those in heart failure who are fluid overloaded.
“It’s phenomenal stuff,” Dr. Mulay said. “You can really stabilize patients’ hemodynamics.”
In the private health care setting, he described widespread enthusiasm among nephrologists, although others still appear skeptical.
“It’s really our cardiology colleagues that I feel are underprescribing it,” Dr. Mulay said. “So, I’m kind of taking it on myself, when I see a heart failure patient, to go ahead and put them on this.”
It’s unclear why some cardiologists seem apprehensive, Dr. Mulay continued, although he suggested that unclear guidelines and a lack of first-hand experience may be to blame.
Nephrologists and cardiologists sometimes agree
In the academic arena, Leslie Gewin, MD, associate professor at Washington University in St. Louis and the John Cochran VA Hospital, also in St. Louis, has seen similar support for SGLT2 inhibitors among both nephrologists and cardiologists.
“We had a joint nephrology-cardiology medicine grand rounds at Wash U in St. Louis maybe 2 weeks ago,” Dr. Gewin said in an interview. “The cardiologists and nephrologists tag-teamed to present data about SGLT2 inhibitors, and we kind of joked that this was the one thing we both could get behind and support.”
Still, she has seen some reluctance among non-nephrology clinicians lacking SGLT2 experience, specifically when managing patients who have poor kidney function.
“There can be some hesitancy among physicians if the GFR is low,” Dr. Gewin said. “That’s where I’ve had to sort of push the envelope with non-nephrologists, saying: ‘Look, we feel pretty comfortable starting down to a GFR of about 20.’ ”
Early rises in creatinine may also spook providers, she noted.
“Sometimes, when we start SGLT2 inhibitors, the creatinine increases slightly, and the [primary care provider] gets concerned,” Dr. Gewin said. “We say: ‘No, this is expected. Don’t worry, hold the course, this is a good drug.’ ”
Like Dr. Mulay, Dr. Gewin said the present study offers further encouragement for the efficacy of this drug class. She also said sufficient data have been published to allay earlier concerns about potential safety signals, such as bone fractures and amputations.
“SGLT2 inhibitors seem to be a lot safer than what we initially had thought,” Dr. Gewin said. “That’s very encouraging.”
The study was funded by AstraZeneca. The investigators disclosed additional relationships with Bayer, Janssen, Gilead, and others. Dr. Gewin and Dr. Mulay disclosed no relevant conflicts of interest.
These findings add to a growing body of evidence supporting a range of positive benefits from dapagliflozin, including reduced risks of mortality, cardiovascular events, and kidney events, lead author Meir Schechter, MD, PhD, of the Hebrew University of Jerusalem and colleagues wrote in Annals of Internal Medicine.“Although cardiovascular and kidney outcomes with SGLT2 inhibitors have been studied extensively, there is a paucity of data evaluating the effects of SGLT2 inhibitors on hospitalizations for any cause.”
The findings are based on a post hoc analysis of the DAPA-CKD trial, which involved 4,304 patients with CKD in 21 countries. Patients were randomized in a 1:1 ratio to receive dapagliflozin 10 mg orally once a day or matching placebo. The present analysis quantified first hospitalizations for any cause, all hospitalizations, cause-specific hospitalizations, and several related outcomes.
After a median follow-up of 2.4 years, 28% of the population had been hospitalized a total of 2,072 times.
Compared with placebo, dapagliflozin significantly reduced risk of first hospitalization by 16% (hazard ratio, 0.84; 95% confidence interval, 0.75-0.94) and rate of all hospitalizations by 21% (rate ratio, 0.79; 95% CI, 0.70-0.89). These findings remained significant regardless of type 2 diabetes status, with significant benefits seen across reasons for admission, including renal/urinary disorders, cardiac disorders, neoplasms, and metabolism/nutrition disorders. In addition, dapagliflozin was associated with shorter mean time in hospital (2.3 vs. 2.8 days; P = .027) and longer time alive and out of hospital (354.9 vs. 351.7; P = .023).
“These findings highlight additional benefits of dapagliflozin beyond those seen for cardiovascular and kidney events, all-cause and cause-specific mortality, eGFR [estimated glomerular filtration rate] slope, and albuminuria and should be considered when evaluating the totality of evidence favoring provision of dapagliflozin to patients with CKD,” the investigators concluded.
Positive data, positive experiences
Shree Mulay, MD, a nephrologist in private practice in western Tennessee, said this study is “one of several other articles that already exist” demonstrating the broad benefits of SGLT2 inhibitors.
“The evidence is pretty substantial,” Dr. Mulay said in an interview. “I think SGLT2 inhibitors are the new statin of this era. ... I won’t be surprised if in the next year or 2 or 3 they truly become the standard of care.”
Dr. Mulay also speaks from experience working in both the chronic and acute setting, where he’s observed “some magical stuff happening” in patients started on SGLT2 inhibitors, especially those in heart failure who are fluid overloaded.
“It’s phenomenal stuff,” Dr. Mulay said. “You can really stabilize patients’ hemodynamics.”
In the private health care setting, he described widespread enthusiasm among nephrologists, although others still appear skeptical.
“It’s really our cardiology colleagues that I feel are underprescribing it,” Dr. Mulay said. “So, I’m kind of taking it on myself, when I see a heart failure patient, to go ahead and put them on this.”
It’s unclear why some cardiologists seem apprehensive, Dr. Mulay continued, although he suggested that unclear guidelines and a lack of first-hand experience may be to blame.
Nephrologists and cardiologists sometimes agree
In the academic arena, Leslie Gewin, MD, associate professor at Washington University in St. Louis and the John Cochran VA Hospital, also in St. Louis, has seen similar support for SGLT2 inhibitors among both nephrologists and cardiologists.
“We had a joint nephrology-cardiology medicine grand rounds at Wash U in St. Louis maybe 2 weeks ago,” Dr. Gewin said in an interview. “The cardiologists and nephrologists tag-teamed to present data about SGLT2 inhibitors, and we kind of joked that this was the one thing we both could get behind and support.”
Still, she has seen some reluctance among non-nephrology clinicians lacking SGLT2 experience, specifically when managing patients who have poor kidney function.
“There can be some hesitancy among physicians if the GFR is low,” Dr. Gewin said. “That’s where I’ve had to sort of push the envelope with non-nephrologists, saying: ‘Look, we feel pretty comfortable starting down to a GFR of about 20.’ ”
Early rises in creatinine may also spook providers, she noted.
“Sometimes, when we start SGLT2 inhibitors, the creatinine increases slightly, and the [primary care provider] gets concerned,” Dr. Gewin said. “We say: ‘No, this is expected. Don’t worry, hold the course, this is a good drug.’ ”
Like Dr. Mulay, Dr. Gewin said the present study offers further encouragement for the efficacy of this drug class. She also said sufficient data have been published to allay earlier concerns about potential safety signals, such as bone fractures and amputations.
“SGLT2 inhibitors seem to be a lot safer than what we initially had thought,” Dr. Gewin said. “That’s very encouraging.”
The study was funded by AstraZeneca. The investigators disclosed additional relationships with Bayer, Janssen, Gilead, and others. Dr. Gewin and Dr. Mulay disclosed no relevant conflicts of interest.
These findings add to a growing body of evidence supporting a range of positive benefits from dapagliflozin, including reduced risks of mortality, cardiovascular events, and kidney events, lead author Meir Schechter, MD, PhD, of the Hebrew University of Jerusalem and colleagues wrote in Annals of Internal Medicine.“Although cardiovascular and kidney outcomes with SGLT2 inhibitors have been studied extensively, there is a paucity of data evaluating the effects of SGLT2 inhibitors on hospitalizations for any cause.”
The findings are based on a post hoc analysis of the DAPA-CKD trial, which involved 4,304 patients with CKD in 21 countries. Patients were randomized in a 1:1 ratio to receive dapagliflozin 10 mg orally once a day or matching placebo. The present analysis quantified first hospitalizations for any cause, all hospitalizations, cause-specific hospitalizations, and several related outcomes.
After a median follow-up of 2.4 years, 28% of the population had been hospitalized a total of 2,072 times.
Compared with placebo, dapagliflozin significantly reduced risk of first hospitalization by 16% (hazard ratio, 0.84; 95% confidence interval, 0.75-0.94) and rate of all hospitalizations by 21% (rate ratio, 0.79; 95% CI, 0.70-0.89). These findings remained significant regardless of type 2 diabetes status, with significant benefits seen across reasons for admission, including renal/urinary disorders, cardiac disorders, neoplasms, and metabolism/nutrition disorders. In addition, dapagliflozin was associated with shorter mean time in hospital (2.3 vs. 2.8 days; P = .027) and longer time alive and out of hospital (354.9 vs. 351.7; P = .023).
“These findings highlight additional benefits of dapagliflozin beyond those seen for cardiovascular and kidney events, all-cause and cause-specific mortality, eGFR [estimated glomerular filtration rate] slope, and albuminuria and should be considered when evaluating the totality of evidence favoring provision of dapagliflozin to patients with CKD,” the investigators concluded.
Positive data, positive experiences
Shree Mulay, MD, a nephrologist in private practice in western Tennessee, said this study is “one of several other articles that already exist” demonstrating the broad benefits of SGLT2 inhibitors.
“The evidence is pretty substantial,” Dr. Mulay said in an interview. “I think SGLT2 inhibitors are the new statin of this era. ... I won’t be surprised if in the next year or 2 or 3 they truly become the standard of care.”
Dr. Mulay also speaks from experience working in both the chronic and acute setting, where he’s observed “some magical stuff happening” in patients started on SGLT2 inhibitors, especially those in heart failure who are fluid overloaded.
“It’s phenomenal stuff,” Dr. Mulay said. “You can really stabilize patients’ hemodynamics.”
In the private health care setting, he described widespread enthusiasm among nephrologists, although others still appear skeptical.
“It’s really our cardiology colleagues that I feel are underprescribing it,” Dr. Mulay said. “So, I’m kind of taking it on myself, when I see a heart failure patient, to go ahead and put them on this.”
It’s unclear why some cardiologists seem apprehensive, Dr. Mulay continued, although he suggested that unclear guidelines and a lack of first-hand experience may be to blame.
Nephrologists and cardiologists sometimes agree
In the academic arena, Leslie Gewin, MD, associate professor at Washington University in St. Louis and the John Cochran VA Hospital, also in St. Louis, has seen similar support for SGLT2 inhibitors among both nephrologists and cardiologists.
“We had a joint nephrology-cardiology medicine grand rounds at Wash U in St. Louis maybe 2 weeks ago,” Dr. Gewin said in an interview. “The cardiologists and nephrologists tag-teamed to present data about SGLT2 inhibitors, and we kind of joked that this was the one thing we both could get behind and support.”
Still, she has seen some reluctance among non-nephrology clinicians lacking SGLT2 experience, specifically when managing patients who have poor kidney function.
“There can be some hesitancy among physicians if the GFR is low,” Dr. Gewin said. “That’s where I’ve had to sort of push the envelope with non-nephrologists, saying: ‘Look, we feel pretty comfortable starting down to a GFR of about 20.’ ”
Early rises in creatinine may also spook providers, she noted.
“Sometimes, when we start SGLT2 inhibitors, the creatinine increases slightly, and the [primary care provider] gets concerned,” Dr. Gewin said. “We say: ‘No, this is expected. Don’t worry, hold the course, this is a good drug.’ ”
Like Dr. Mulay, Dr. Gewin said the present study offers further encouragement for the efficacy of this drug class. She also said sufficient data have been published to allay earlier concerns about potential safety signals, such as bone fractures and amputations.
“SGLT2 inhibitors seem to be a lot safer than what we initially had thought,” Dr. Gewin said. “That’s very encouraging.”
The study was funded by AstraZeneca. The investigators disclosed additional relationships with Bayer, Janssen, Gilead, and others. Dr. Gewin and Dr. Mulay disclosed no relevant conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
FDA alert: ‘Substantial’ hypocalcemia risk with denosumab use in dialysis patients
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration issued an alert on Nov. 22 that cited preliminary evidence for a “substantial risk” for severe and symptomatic hypocalcemia and serious outcomes related to abnormally low calcium levels in people being treated with dialysis and receiving the osteoporosis medication denosumab (Prolia), including hospitalization and death.
In its alert, the FDA advised clinicians to make sure that people on dialysis who receive Prolia ingest adequate calcium and vitamin D supplementation and undergo frequent blood calcium monitoring, “possibly more often than is already being conducted,” which “may help decrease the likelihood or severity of these risks.”
The agency also called on clinicians to “advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia,” such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.
The FDA had a similar message for people being treated with dialysis who are also receiving Prolia. The alert advised patients to watch for these symptoms and to tell their health care provider if they occur. The agency also advised patients who are undergoing dialysis and receiving Prolia to not stop the agent on their own, without first discussing this step with their care provider.
The FDA also advised providers and patients to contact the agency about episodes of side effects from Prolia (or other medications) via the FDA’s MedWatch program.
Frequent and serious
The FDA explained it issued the alert because of “the frequency and seriousness” of the risk for hypocalcemia and resulting complications. The agency noted that the risk seems most acute for people on dialysis who also receive Prolia, but the risk may also extend to people with advanced kidney disease who are not being treated with hemodialysis.
The alert stemmed from “interim results” in an ongoing safety study of Prolia that the FDA required the agent’s manufacturer, Amgen, to run when the agency first approved denosumab for U.S. marketing in 2010. The FDA said its review of these interim results suggested an increased risk of hypocalcemia with Prolia in patients with advanced kidney disease.
In addition, adverse event reports submitted to the FDA suggested in a separate, internal study that patients on dialysis treated with Prolia are at “substantial risk for severe and symptomatic hypocalcemia, including hospitalization and death.”
The alert explained that “because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis.” The FDA added that “we will communicate our final conclusions and recommendations when we have completed our review or have more information to share.”
A version of this article first appeared on Medscape.com.
Balanced crystalloid fluids surpass saline for kidney transplant
ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.
“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.
“Balanced crystalloids are cheap, readily available worldwide, and this simple change in kidney transplant practice can easily be implemented in global practice ... almost immediately,” said Dr. Collins, a nephrologist at Royal Adelaide Hospital, Australia.
A 1-L bag of balanced crystalloid fluid is more expensive; however, it has a U.S. retail cost of about $2-$5 per bag, compared with about $1 per bag of saline fluid, Dr. Collins added.
Various other commentators had mixed views. Some agreed with Dr. Collins and said the switch could be made immediately, although one researcher wanted to see more trials. Another wondered why balanced crystalloid fluid hadn’t seemed to provide benefit in studies in acute kidney injury.
Treating 10 patients prevents one delayed graft function
The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.
This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.
Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.
A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.
Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
Chloride is the culprit
“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.
“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.
However, Pascale H. Lane, MD, a pediatric nephrologist with Oklahoma University Health, Oklahoma City, predicted that based on these results, “I think it will be rapidly embraced” by U.S. clinicians. Dr. Lane expressed concern about the availability of an adequate supply of balanced crystalloid fluid, but Dr. Collins said he did not believe supply would be an issue based on current availability.
This was “a beautiful study, very well done, with nice results, and a very easy switch to balanced crystalloid fluids without harm,” commented Richard Lafayette, MD, a nephrologist and professor of medicine at Stanford (Calif.) University.
Success attributed to early treatment
But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.
Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.
The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.
Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.
During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.
The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.
BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.
A version of this article first appeared on Medscape.com.
ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.
“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.
“Balanced crystalloids are cheap, readily available worldwide, and this simple change in kidney transplant practice can easily be implemented in global practice ... almost immediately,” said Dr. Collins, a nephrologist at Royal Adelaide Hospital, Australia.
A 1-L bag of balanced crystalloid fluid is more expensive; however, it has a U.S. retail cost of about $2-$5 per bag, compared with about $1 per bag of saline fluid, Dr. Collins added.
Various other commentators had mixed views. Some agreed with Dr. Collins and said the switch could be made immediately, although one researcher wanted to see more trials. Another wondered why balanced crystalloid fluid hadn’t seemed to provide benefit in studies in acute kidney injury.
Treating 10 patients prevents one delayed graft function
The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.
This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.
Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.
A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.
Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
Chloride is the culprit
“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.
“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.
However, Pascale H. Lane, MD, a pediatric nephrologist with Oklahoma University Health, Oklahoma City, predicted that based on these results, “I think it will be rapidly embraced” by U.S. clinicians. Dr. Lane expressed concern about the availability of an adequate supply of balanced crystalloid fluid, but Dr. Collins said he did not believe supply would be an issue based on current availability.
This was “a beautiful study, very well done, with nice results, and a very easy switch to balanced crystalloid fluids without harm,” commented Richard Lafayette, MD, a nephrologist and professor of medicine at Stanford (Calif.) University.
Success attributed to early treatment
But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.
Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.
The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.
Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.
During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.
The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.
BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.
A version of this article first appeared on Medscape.com.
ORLANDO – Using a low-chloride, balanced crystalloid solution for all intravenous fluids received by patients who received a deceased donor kidney transplant resulted in significantly fewer episodes of delayed graft function, compared with patients who received saline as their IV fluids, in a new multicenter trial with 807 randomized and evaluable patients called BEST-Fluids.
“The findings suggest that balanced crystalloids should be the standard-of-care IV fluid in deceased donor kidney transplantations,” Michael G. Collins, MBChB, PhD, said at the annual meeting of the American Society of Nephrology.
“Balanced crystalloids are cheap, readily available worldwide, and this simple change in kidney transplant practice can easily be implemented in global practice ... almost immediately,” said Dr. Collins, a nephrologist at Royal Adelaide Hospital, Australia.
A 1-L bag of balanced crystalloid fluid is more expensive; however, it has a U.S. retail cost of about $2-$5 per bag, compared with about $1 per bag of saline fluid, Dr. Collins added.
Various other commentators had mixed views. Some agreed with Dr. Collins and said the switch could be made immediately, although one researcher wanted to see more trials. Another wondered why balanced crystalloid fluid hadn’t seemed to provide benefit in studies in acute kidney injury.
Treating 10 patients prevents one delayed graft function
The incidence of delayed graft function, defined as the need for dialysis during the 7 days following transplantation, occurred in 30.0% of 404 patients who received balanced crystalloid fluids (Plasma-Lyte 148) and in 39.7% of 403 patients who received saline starting at the time of randomization (prior to surgery) until 48 hours post-surgery, Dr. Collins reported.
This translated into a significant, adjusted relative risk reduction of 26% and a number needed to treat of 10 to result in one avoided episode of delayed graft function.
Preventing delayed graft function is important because it is a “major complication” of deceased donor kidney transplantation that usually occurs in about 30%-50% of people who receive these organs, Dr. Collins explained. Incident delayed graft function leads to higher hospitalization costs because of a prolonged need for dialysis and extended hospital days, as well as increased risk for long-term graft failure and death.
A secondary outcome – the number of dialysis sessions required during the 28 days following transplantation – was 406 sessions among those who received balanced crystalloid fluids and 596 sessions among the controls who received saline, a significant adjusted relative decrease of 30%.
Freedom from need for dialysis by 12 weeks after surgery increased by a significant 10% among those treated with balanced crystalloid fluids, compared with controls. The balanced crystalloid fluids were also significantly linked with an average 1-L increase in urine output during the first 2 days after transplantation, compared with controls.
Chloride is the culprit
“I think this is driven by the harmful effects of saline,” which is currently the standard fluid that kidney transplant patients receive worldwide, said Dr. Collins. Specifically, he cited the chloride content of saline – which contains 0.9% sodium chloride – as the culprit by causing reduced kidney perfusion.
“Some data suggest that saline may be harmful because of chloride acidosis producing vasoconstriction and increasing ischemia,” commented Karen A. Griffin, MD, chief of the renal section at the Edward Hines, Jr. VA Medical Center, Hines, Illinois. But Dr. Griffin said she’d like to see further study of balanced crystalloid fluids in this setting before she’d be comfortable using it routinely as a replacement for saline.
However, Pascale H. Lane, MD, a pediatric nephrologist with Oklahoma University Health, Oklahoma City, predicted that based on these results, “I think it will be rapidly embraced” by U.S. clinicians. Dr. Lane expressed concern about the availability of an adequate supply of balanced crystalloid fluid, but Dr. Collins said he did not believe supply would be an issue based on current availability.
This was “a beautiful study, very well done, with nice results, and a very easy switch to balanced crystalloid fluids without harm,” commented Richard Lafayette, MD, a nephrologist and professor of medicine at Stanford (Calif.) University.
Success attributed to early treatment
But Dr. Lafayette also wondered, “Why should this work for transplant patients when it did not work for patients who develop acute kidney injury in the ICU?” And he found it hard to understand how the impact of the balanced crystalloid fluid could manifest so quickly, with a change in urine output during the first day following surgery.
Dr. Collins attributed the rapid effects and overall success to the early initiation of balanced crystalloid fluids before the transplant occurred.
The BEST-Fluids trial ran at 16 centers in Australia and New Zealand and enrolled patients from January 2018 to August 2020. It enrolled adults and children scheduled to receive a deceased donor kidney, excluding those who weighed less than 20 kg and those who received multiple organs.
Enrolled patients averaged about 55 years old, about 63% were men, and their average duration on dialysis prior to surgery was about 30 months. The study randomized 808 patients who received their transplanted kidney, with 807 included in the efficacy analysis. Patients in each of the two groups showed very close balance for all reported parameters of patient and donor characteristics. During the period of randomized fluid treatment, patients in the balanced crystalloid group received an average of just over 8 L of fluid, while those in the control group received an average of just over 7 L.
During follow-up, serious adverse events were rare and balanced, with three in the balanced crystalloid group and four among controls.
The only significant difference in adverse events was the rate of ICU admissions that required ventilation, which occurred in one patient in the balanced crystalloid group and 12 controls.
BEST-Fluids received balanced crystalloid and saline solutions at no charge from Baxter Healthcare, which markets Plasma-Lyte 148. The study received no other commercial funding. Dr. Collins, Dr. Griffin, and Dr. Lane have reported no relevant financial relationships. Dr. Lafayette has received personal fees and grants from Alexion, Aurinia, Calliditas, Omeros, Pfizer, Roche, Travere, and Vera and has been an advisor to Akahest and Equillium.
A version of this article first appeared on Medscape.com.
AT KIDNEY WEEK 2022
EHR alerts flag acute kidney injury and avert progression
ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.
“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.
In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.
“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.
“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.
“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
A danger for alert fatigue
But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”
Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”
Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.
These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
Targeting NSAIDS, RAAS inhibitors, and PPIs
The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).
“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.
The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.
The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.
The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
Overall, a 9% relative increase in discontinuations
In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.
Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.
Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.
Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.
The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.
Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.
A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
PPIs may distinguish ‘sicker’ patients
Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.
In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.
PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.
The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.
The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.
“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.
In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.
“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.
“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.
“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
A danger for alert fatigue
But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”
Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”
Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.
These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
Targeting NSAIDS, RAAS inhibitors, and PPIs
The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).
“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.
The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.
The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.
The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
Overall, a 9% relative increase in discontinuations
In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.
Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.
Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.
Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.
The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.
Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.
A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
PPIs may distinguish ‘sicker’ patients
Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.
In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.
PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.
The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.
The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO – Automated alerts sent to clinicians via patients’ electronic health records identified patients with diagnosable acute kidney injury (AKI) who were taking one or more medications that could potentially further worsen their renal function. This led to a significant increase in discontinuations of the problematic drugs and better clinical outcomes in a subgroup of patients in a new multicenter, randomized study with more than 5,000 participants.
“Automated alerts for AKI can increase the rate of cessation of potentially nephrotoxic medications without endangering patients,” said F. Perry Wilson, MD, at Kidney Week 2022, organized by the American Society of Nephrology.
In addition, the study provides “limited evidence that these alerts change clinical practice,” said Dr. Wilson, a nephrologist and director of the clinical and translational research accelerator at Yale School of Medicine in New Haven, Conn.
“It was encouraging to get providers to change their behavior” by quickly stopping treatment with potentially nephrotoxic medications in patients with incident AKI. But the results also confirmed that “patient decision-support systems tend to not be panaceas,” Dr. Wilson explained in an interview. Instead, “they tend to marginally improve” patients’ clinical status.
“Our hope is that widespread use may make some difference on a population scale, but rarely are these game changers,” he admitted.
“This was a very nice study showing how we can leverage the EHR to look not only at drugs but also contrast agents to direct educational efforts aimed at clinicians about when to discontinue” these treatments, commented Karen A. Griffin, MD, who was not involved with the study.
A danger for alert fatigue
But the results also showed that more research is needed to better refine this approach, added Dr. Griffin, a professor at Loyola University Chicago, Maywood, Ill., and chief of the renal section at the Edward Hines Jr. VA Medical Center in Hines, Ill. And she expressed caution about expanding the alerts that clinicians receive “because of the potential for alert fatigue.”
Dr. Wilson also acknowledged the danger for alert fatigue. “We’re doing these studies to try to reduce the number of alerts,” he said. “Most clinicians say that if we could show an alert improves patient outcomes, they would embrace it.”
Dr. Wilson and associates designed their current study to evaluate an enhanced type of alert that not only warned clinicians that a patient had developed AKI but also gave them an option to potentially intervene by stopping treatment with a medication that could possibly exacerbate worsening renal function. This enhancement followed their experience in a 2021 study that tested a purely informational alert that gave physicians no guidance about what actions to take to more quickly resolve the AKI.
These findings plus results from other studies suggested that “purely informational alerts may not be enough. They need to be linked” to suggested changes in patient management, Dr. Wilson explained.
Targeting NSAIDS, RAAS inhibitors, and PPIs
The new study used automated EHR analysis to not only identify patients with incident AKI, but also to flag medications these patients were receiving from any of three classes suspected of worsening renal function: nonsteroidal anti-inflammatory drugs, renin-angiotensin-aldosterone system (RAAS) inhibitors (which include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), and proton-pump inhibitors (PPIs).
“Our hypothesis was that giving clinicians actionable advice could significantly improve patient outcomes,” Dr. Wilson said. “NSAIDs are frequently discontinued” in patients who develop AKI. “RAAS inhibitors are sometimes discontinued,” although the benefit from doing this remains unproven and controversial. “PPIs are rarely discontinued,” and may be an underappreciated contributor to AKI by causing interstitial nephritis in some patients.
The prospective study included 5,060 adults admitted with a diagnosis of stage 1 AKI at any of four Yale-affiliated teaching hospitals who were also taking agents from at least one of the three targeted drug classes at the time of admission. Clinicians caring for 2,532 of these patients received an alert about the AKI diagnosis and use of the questionable medications, while those caring for the 2,528 control patients received no alert and delivered usual care.
The study excluded patients with higher-risk profiles, including those with extremely elevated serum creatinine levels at admission (4.0 mg/dL or higher), those recently treated with dialysis, and patients with end-stage kidney disease.
The study had two primary outcomes. One measured the impact of the intervention on stopping the targeted drugs. The second assessed the clinical effect of the intervention on progression of AKI to a higher stage, need for dialysis, or death during either the duration of hospitalization or during the first 14 days following randomization.
Overall, a 9% relative increase in discontinuations
In general, the intervention had a modest but significant effect on cessation of the targeted drug classes within 24 hours of sending the alert.
Overall, there was about a 58% discontinuation rate among controls and about a 62% discontinuation rate among patients managed using the alerts, a significant 9% relative increase in any drug discontinuation, Dr. Wilson reported.
Discontinuations of NSAIDs occurred at the highest rate, in about 80% of patients in both groups, and the intervention showed no significant effect on stopping agents from this class. Discontinuations of RAAS inhibitors showed the largest absolute difference in between-group effect, about a 10–percentage point increase that represented a significant 14% relative increase in stopping agents from this class. Discontinuations of PPIs occurred at the lowest rate, in roughly 20% of patients, but the alert intervention had the greatest impact by raising the relative rate of stopping by a significant 26% compared with controls.
Analysis of the effect of the intervention on the combined clinical outcome showed a less robust impact. The alerts produced no significant change in the clinical outcome overall, or in the use of NSAIDs or RAAS inhibitors. However, the change in use of PPIs following the alerts significantly linked with a 12% relative drop in the incidence of the combined clinical endpoint of progression of AKI to a higher stage, need for dialysis, or death.
The results were consistent across several prespecified subgroups based on parameters such as age, sex, and race, but these analyses showed a signal that the alerts were most helpful for patients who had serum creatinine levels at admission of less than 0.5 mg/dL.
Dr. Wilson speculated that the alerts might have been especially effective for these patients because their low creatinine levels might otherwise mask AKI onset.
A safety analysis showed no evidence that the alert interventions and drug cessations increased the incidence of any complications.
PPIs may distinguish ‘sicker’ patients
Dr. Wilson cited two potential explanations for why the tested alerts appeared most effective for patients taking a PPI at the time of admission. One is that PPIs are underappreciated as a contributor to AKI, a possibility supported by the low rates of discontinuation in both the control and intervention groups.
In addition, treatment with a PPI may be a marker of “sicker” patients who may have more to gain from quicker identification of their AKI. For example, 28% of the patients who were taking a PPI at admission were in the ICU when they entered the study compared with a 14% rate of ICU care among everyone else.
PPIs were also the most-used targeted drug class among enrolled patients, used by 65% at baseline, compared with 53% who were taking a RAAS inhibitor and about 31% who were taking an NSAID. About 6% of enrolled patients were taking agents from all three classes at baseline, and 36% were on treatment with agents from two of the classes.
The next step is to assess adding more refinement to the alert process, Dr. Wilson said. He and his associates are now running a study in which an AKI alert goes to a “kidney action team” that includes a trained clinician and a pharmacist. The team would review the patient who triggered the alert and quickly make an individualized assessment of the best intervention for resolving the AKI.
The study received no commercial funding. Dr. Wilson has received research funding from AstraZeneca, Boehringer Ingelheim, Vifor, and Whoop. Dr. Griffin has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT KIDNEY WEEK 2022
Dialysis not always best option in advanced kidney disease
ORLANDO – , new research shows.
“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.
“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.
The results were presented during the annual meeting of the American Society of Nephrology.
“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.
“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.
Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.
“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.
“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
Study details
In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m2) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m2 at dialysis initiation).
Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.
“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.
In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.
Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
Conservative care has pros and cons, but Canada has embraced it
As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”
On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.
But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.
Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.
“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.
“But it’s not that they do not believe in the value of CKM.”
Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.
“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.
“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO – , new research shows.
“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.
“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.
The results were presented during the annual meeting of the American Society of Nephrology.
“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.
“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.
Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.
“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.
“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
Study details
In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m2) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m2 at dialysis initiation).
Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.
“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.
In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.
Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
Conservative care has pros and cons, but Canada has embraced it
As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”
On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.
But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.
Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.
“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.
“But it’s not that they do not believe in the value of CKM.”
Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.
“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.
“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO – , new research shows.
“Patients mostly start dialysis because of unpleasant symptoms that cause suffering, including high potassium levels and high levels of uremic toxins in the blood,” senior author Kamyar Kalantar-Zadeh, MD, PhD, MPH, told this news organization.
“Conservative management serves to address and manage these symptoms and levels of toxicities without dialysis, so conservative management is an alternative approach, and patients should always be given a choice between [the two],” stressed Dr. Kalantar-Zadeh, professor of medicine at the University of California, Irvine.
The results were presented during the annual meeting of the American Society of Nephrology.
“There has been growing recognition of the importance of conservative nondialytic management as an alternative patient-centered treatment strategy for advanced kidney disease. However, conservative management remains under-utilized in the United States, which may in part be due to uncertainties regarding which patients will most benefit from dialysis versus nondialytic treatment,” said first author Connie Rhee, MD, also of the University of California, Irvine.
“We hope that these findings and further research can help inform treatment options for patients, care partners, and providers in the shared decision-making process of conservative management versus dialysis,” added Dr. Rhee, in a press release from the American Society of Nephrology.
Asked for comment, Sarah Davison, MD, noted that part of the Society’s strategy is, in fact, to promote conservative kidney management (CKM) as a key component of integrated care for patients with kidney failure. Dr. Davison is professor of medicine and chair of the International Society Working Group for Kidney Supportive Care and Conservative Kidney Management.
“We’ve recognized for a long time that there are many patients for whom dialysis provides neither a survival advantage nor a quality of life advantage,” she told this news organization.
“These patients tend to be those who have multiple morbidities, who are more frail, and who tend to be older, and in fact, the patients can live as long, if not longer, with better symptom management and better quality of life by not being on dialysis,” she stressed.
Study details
In the study, using data from the Optum Labs Data Warehouse, patients with advanced CKD were categorized according to whether or not they received conservative management, defined as those who did not receive dialysis within 2 years of the index eGFR (first eGFR < 25 mL/min/1.73m2) versus receipt of dialysis parsed as late versus early dialysis transition (eGFR < 15 vs. ≥ 15 mL/min/1.73m2 at dialysis initiation).
Hospitalization rates were compared between those treated with conservative management, compared with late or early dialysis.
“Among 309,188 advanced CKD patients who met eligibility [criteria], 55% of patients had greater than or equal to 1 hospitalization(s) within 2 years of the index eGFR,” the authors report. The most common causes of hospitalization among all patients were congestive heart failure, respiratory symptoms, or hypertension.
In most racial groups (non-Hispanic White, non-Hispanic Black, and Hispanic patients), patients on dialysis had higher hospitalization rates than those who received conservative management, and patients who started dialysis early (transitioned to dialysis at higher levels of kidney function) demonstrated the highest rates across all age groups, compared with those who started dialysis late (transitioned to dialysis at lower levels of kidney function) or were treated with conservative management.
Among Asian patients, those on dialysis also had higher hospitalization rates than those receiving conservative management, but patients who started dialysis late had higher rates than those on early dialysis, especially in older age groups, possibly because they were sicker, Dr. Kalantar-Zadeh suggested.
Conservative care has pros and cons, but Canada has embraced it
As Dr. Kalantar-Zadeh explained, conservative management has its pros and cons, compared with dialysis. “Conservative management requires that patients work with the multidisciplinary team including nephrologists, nutritionists, and others to try to manage CKD without dialysis, so it requires patient participation.”
On the other hand, dialysis is both easier and more lucrative than conservative management, at least for nephrologists, as they are well-trained in dialysis care, and it can be systematically applied. As to which patients with CKD might be optimal candidates for conservative management, Dr. Kalantar-Zadeh agreed this requires further study.
But he acknowledged that most nephrologists are not hugely supportive of conservative management because they are less well-trained in it, and it is more time-consuming. The one promising change is a new model introduced in 2022, a value-based kidney care model, that, if implemented, will be more incentivizing for nephrologists to offer conservative care more widely.
Dr. Davison meanwhile believes the “vast majority” of nephrologists based in Canada – as she is – are “highly supportive” of CKM as an important modality.
“The challenge, however, is that many nephrologists remain unsure as to how to best deliver or optimize all aspects of CKM, whether that is symptom management, advanced care planning, or how they must manage symptoms to align with a patient’s goals,” Dr. Davison explained.
“But it’s not that they do not believe in the value of CKM.”
Indeed, in her province, Alberta, nephrologists have been offering CKM for decades, and while they are currently standardizing care to make it easier to deliver, there is no financial incentive to offer dialysis over CKM.
“We are now seeing those elements of kidney supportive care as part of core competencies to manage any person with chronic illness, including CKD,” Dr. Davison said.
“So it’s absolutely doable, and contrary to one of the myths about CKM, it is not more time-consuming than dialysis – not when you know how to do it. You are just shifting your focus,” she emphasized.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Kalantar-Zadeh has reported receiving honoraria and medical directorship fees from Fresenius and DaVita. Dr. Davison has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT KIDNEY WEEK 2022