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LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.
During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.
Antihypertensive therapy
Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.
She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.
“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.
The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.
“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.
The problem is that many physicians think 110 or 112 is too low.
“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”
ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.
Hydroxychloroquine
Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.
“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”
Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.
Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.
In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).
“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
Vitamin D
Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.
In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).
“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
Mycophenolate mofetil
The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.
Left untreated, he would be in end-stage renal disease within a year, she said.
“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.
This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.
“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”
In this case, however, the best induction therapy is mycophenolate mofetil, she said.
“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”
In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.
After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”
“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.
“So we really need something that’s much more successful.”
Steroids
How much prednisone should lupus nephritis patients get?
As little as possible, according to Dr. Petri.
“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”
She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.
“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.
“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.
EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”
“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”
Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).
“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”
Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.
“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.
“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).
Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).
Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.
LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.
During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.
Antihypertensive therapy
Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.
She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.
“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.
The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.
“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.
The problem is that many physicians think 110 or 112 is too low.
“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”
ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.
Hydroxychloroquine
Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.
“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”
Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.
Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.
In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).
“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
Vitamin D
Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.
In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).
“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
Mycophenolate mofetil
The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.
Left untreated, he would be in end-stage renal disease within a year, she said.
“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.
This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.
“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”
In this case, however, the best induction therapy is mycophenolate mofetil, she said.
“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”
In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.
After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”
“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.
“So we really need something that’s much more successful.”
Steroids
How much prednisone should lupus nephritis patients get?
As little as possible, according to Dr. Petri.
“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”
She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.
“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.
“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.
EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”
“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”
Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).
“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”
Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.
“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.
“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).
Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).
Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.
LAKE BUENA VISTA, FLA. – When it comes to lupus nephritis, the guidelines – and prevailing wisdom – don’t always get it quite right, according to Michelle A. Petri, MD.
During an update at the annual meeting of the Florida Society of Rheumatology, she outlined five key components of lupus nephritis treatment, and the status of the evidence for each.
Antihypertensive therapy
Antihypertensive therapy isn’t just for hypertension in patients with lupus nephritis – it’s for reducing proteinuria and preventing renal fibrosis, said Dr. Petri, professor of medicine and director of the Hopkins Lupus Center at Johns Hopkins University, Baltimore.
“I get a lot of push-back on this,” she added, explaining that other physicians often will stop the treatment as she prescribed it, because they believe it’s unnecessary.
She described a case involving a 33-year-old African American man with blood pressure of 132/86 mm Hg and grade 3+ ankle edema. Laboratory tests were remarkable for hematocrit (33.4%), white blood cell count (3.1), erythrocyte sedimentation rate (67 mm/hr) and urinalysis (2+ protein by dipstick, 3 red cells/high-power field, no casts). Additionally, 24-hour urine protein showed 400 mg of microalbumin, and he had a positive antinuclear antibody test, positive anti–double stranded DNA, and low complement.
“I’m going to argue really strenuously that he has to be on an ACE inhibitor or an ARB [angiotensin receptor blocker],” she said, explaining that even before an immunosuppressant therapy is started, optimizing ACE inhibitor or ARB therapy can reduce proteinuria by 50%.
The “sweet spot” for blood pressure in these patients is between 110 and 129, she said.
“You don’t want it too low, because you might hurt renal perfusion, but you sure don’t want it above 130,” she said.
The problem is that many physicians think 110 or 112 is too low.
“Not for a lupus nephritis patient,” she said. “It’s really where we want to be.”
ACE inhibitors and ARBs are preferable for reaching this goal, she said, noting that calcium channel blockers have been linked with shorter time to renal failure.
Hydroxychloroquine
Everyone with lupus nephritis should be on hydroxychloroquine, Dr. Petri argued.
“It improves renal outcomes,” she said. “It more than triples the chance that a patient will have a complete renal response.”
Guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) are in agreement on this, she said.
Even the renal guidelines for lupus nephritis now include hydroxychloroquine as mandatory, she added, noting that it is not necessary to check glucose-6-phosphate dehydrogenase (G6PD) before starting treatment.
In fact, a recent study showed that only 2 of 11 patients with G6PD deficiency had episodes of hemolysis, and those episodes did not occur during hydroxychloroquine therapy. The authors concluded that the routine measurement of G6PD levels and withholding therapy among African American patients with G6PD deficiency is not supported, she said (Arthritis Care Res. 2018;70[3]:481-5).
“Of course, if your patient has renal insufficiency you’re going to have to reduce the dose in half,” she noted.
Vitamin D
Modestly increasing 25-hydroxyvitamin D can “greatly, significantly reduce the urine protein – with no cost, with no toxicity,” Dr. Petri said.
In a 2013 study, she and her colleagues showed that a 20‐ng/mL increase in the 25(OH)vitamin D level was associated with a 21% decrease in the odds of having a high disease-activity score, and with a 15% decrease in the odds of having clinically important proteinuria (Arthritis Rheumatol. 2013;65[7]:1865-71).
“But you’ll be fascinated to hear that vitamin D may be an antifibrotic drug, as well,” she noted. “This has been proven in animal models of pulmonary fibrosis ... and although we don’t have proof in lupus nephritis, the animal models are so strong that I think absolutely everybody with lupus nephritis needs to be on vitamin D, both to reduce proteinuria and then, hopefully, as a very cheap antifibrotic drug.”
Mycophenolate mofetil
The case Dr. Petri presented involved a patient with International Society of Nephrology class IV disease.
Left untreated, he would be in end-stage renal disease within a year, she said.
“But even with my maximal treatment he has a 23% chance of being in end-stage renal disease in 20 years,” she noted.
This patient had a high National Institutes of Health activity index, but low chronicity, and there were no crescents.
“The reason I mention this is because crescents mean rapidly progressive [glomerular nephritis],” she said. “That’s very urgent; it’s one of the situations where even I will dump on the steroids, because you’ve got to do something fast.”
In this case, however, the best induction therapy is mycophenolate mofetil, she said.
“Boy, our guidelines are wishy-washy on this, and they shouldn’t be,” she said, explaining that “because he’s African American, there are very clear data that mycophenolate is better than cyclophosphamide – our guidelines need to make that very clear.”
In fact, mycophenolate should be the first choice of induction therapy in all cases, except those involving rapidly progressive glomerulonephritis (RPGN), for which cyclophosphamide should be given for at least 3 months before trying to transition to mycophenolate, she stressed.
After about 1 year of treatment, 50% of patients will be complete renal responders, she noted, adding that “in Caucasians, mycophenolate is as good as cyclophosphamide, and in African Americans, mycophenolate is much better.”
“So mycophenolate has won, and for good reason. But is it sufficient to have 50% of patients be complete renal responders at 1 year?” she asked, noting the risk for renal fibrosis in those who respond late in that year or not at all.
“So we really need something that’s much more successful.”
Steroids
How much prednisone should lupus nephritis patients get?
As little as possible, according to Dr. Petri.
“I want you to think back to all those times you were taught during you fellowship about dumping on as much prednisone as possible,” she said. “[They] probably aren’t correct.”
She also pulled no punches when it comes to the ACR and EULAR guidelines on prednisone use.
“Both ... are wrong,” she said, explaining that the ACR guidelines are “top-heavy” on prednisone in calling for 0.5-1 mg/kg/day.
“One mg/kg? Like everybody’s the same? I do not object to 1 mg/kg if it’s RPGN, but not for everybody else,” she said.
EULAR guidelines are “less generous,” calling for 0.5 mg/kg/day for 4 weeks, and they make it clear that “you better taper that stuff off.”
“I like that part,” she said. “But still, you’re starting out with a lot of steroid.”
Why the objection? Data show that prednisone is directly or indirectly responsible for 80% of organ damage over 15 years, she said (J Rheumatol. 2003;30[9]:1955-9).
“It’s bad enough to have lupus nephritis; why should you have to be poisoned with prednisone, as well?” she asked. “Now, if the people on prednisone did better, of course I’d have to back off, wouldn’t I?”
Recent data, however, suggest that lupus nephritis patients who are treated with prednisone end up doing worse, and studies being performed outside the United States are beginning to use lower doses of prednisone, she said.
“The rest of the world is lowering the prednisone; our guidelines need to catch up,” she said, adding that she sees no reason why this shouldn’t apply in lupus nephritis.
“Their prednisone should be less than 6 mg, and doses above that level increase organ damage by 50%,” she said, citing a 2009 study in which she and her colleagues found that the hazard ratio for organ damage with prednisone vs. no prednisone was 1.50 for cumulative average doses of 180-360 mg/month, compared with 1.16 for doses up to 180 mg/month (J Rheumatol. 2009;36[3]:560-4).
Even a 20-mg dose has been linked with a fivefold increase the risk of a vascular incident, she added, citing another such study (Am J Epidemiol. 2012;176:708-19).
Dr. Petri is a consultant for GlaxoSmithKline, Merck EMD Serono, Lilly, Janssen, Amgen, Novartis, Exagen, Inova Diagnostics, AstraZeneca, Blackrock Pharma, Glenmark, and UCB.
REPORTING FROM FSR 2019