ASN Kidney Week 2013

ATLANTA – A novel first-in-class agent that selectively binds cations appears safe and effective for the treatment of hyperkalemia in patients with chronic kidney disease, according to findings from a phase II, dose-ranging proof-of-concept study.

Preliminary data from a phase III study of 753 patients, which was initiated based on the positive findings in the phase II study, similarly demonstrate the safety and efficacy of the selective monovalent cation trap known as ZS-9 (ZS Pharma), Dr. Stephen R. Ash reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

In 90 patients from the phase II study who were randomized to receive either placebo or one of three ZS-9 doses (0.3 g in 12 patients, 3 g in 24 patients, and 10 g in 24 patients), active treatment was associated with significantly greater dose-dependent reductions in serum potassium (K+) than was placebo, said Dr. Ash of Indiana University, Lafayette.

The mean serum K+ level at baseline for both the placebo group and the combined active treatment groups was 5.1 mEq/L. Within 48 hours of treatment initiation, 63% of patients in the 10-g ZS-9 group met the primary end point of at least a 1.0-mEq/L reduction in serum K+, compared with only 17% of patients in the placebo group.

The dose reduction in the 10-g group was "rapid and substantial," with a significant decrease, compared with placebo, occurring within 1 hour of the initial dose. Levels were 0.92-mEq/L lower than baseline after 38 hours (4 hours after the last dose), and 0.68-mEq/L lower than baseline at 48 hours (14 hours after the last dose). The levels remained significantly lower than placebo for an additional 3.5 days after the last dose, Dr. Ash said.

"At every point in the trial for these 10-g–dose patients, the serum potassium was lower in the treatment group than in the control group. ... At 38 hours, almost 90% of the patients who were on the 10-g dose had a serum potassium [level] of less than 4.5," he said.

Participants had mild to moderate chronic kidney disease with a glomerular filtration rate of 30-60 mL/min per 1.73 m², and mild to moderate hyperkalemia, with serum K+ levels of 5-6 mEq/L.

Treatment with the tasteless, odorless substance, which was delivered orally as a suspension in water three times daily at meal times, was well tolerated. No serious adverse events were reported, and no significant gastrointestinal issues, hypokalemia, hypomagnesemia, or hypocalcemia were observed.

Only one adverse event, a mild case of constipation in the 3-g–dose group, was thought to have a causal relationship to the study drug. No patients withdrew from the study.

The preliminary data from the pivotal randomized, controlled phase III trial also suggest a rapid and dose-dependent reduction in serum K+ in patients treated with ZS-9. In that study, patients were randomized to receive placebo or ZS-9 at doses of 1.25 g, 2.5 g, 5 g, or 10 g three times daily for the initial 48 hours.

Patients whose serum K+ levels normalized during that initial phase of treatment were then randomized to receive placebo or one of the four active drug doses administered daily for 12 days.

Patients in the phase III trial had serum K+ levels of 5-6.5 mEq/L. Those in the 2.5-g, 5-g, and 10-g groups met the primary endpoint, with significantly greater reductions in serum K+, compared with those on placebo, at 48 hours.

The mean serum K+ reduction was 0.73 mEq/L at the 10-g dose at 48 hours. The gastrointestinal adverse event rate was 5.1% in the placebo group patients, and 3.5% in the treatment group.

Final results from the phase III trial are expected in the coming months.

The findings are important because currently only one treatment – sodium polystyrene sulfonate (SPS), an organic polymer resin that nonselectively binds cations – is approved in the United States for the treatment of hyperkalemia – a serious condition that is associated with significant mortality and morbidity in patients with cardiovascular disease or chronic kidney disease.

"Even marginally high potassium levels, such as over 4.5, however, have an increased risk of death and ventricular fibrillation," Dr. Ash explained.

Further, hyperkalemia limits the ability to use cardioprotective and renoprotective agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, he said.

The efficacy of SPS for lowering serum K+ levels is questionable, and the agent has been associated with several serious adverse effects, including sodium loading, colonic necrosis, and other fatal gastrointestinal effects, Dr. Ash explained.

ZS-9 differs from traditional nonspecific and nonselective cation exchange organic polymer resins in that it is an inorganic cation exchanger – a result of advances in chemistry for the development of highly selective drug therapies.

"ZS-9 was designed and engineered to be highly selective for potassium," he said, noting that ZS-9 has more than nine times the potassium-binding ability of SPS, and is not systemically absorbed; thus, the risk of systemic toxicity is minimized or eliminated.

The findings thus far suggest that ZS-9 is a safe, reliable, fast, effective and well-tolerated therapy for lowering serum K+ levels in patients with hyperkalemia, Dr. Ash concluded.

Dr. Ash disclosed ties with Merit Medical, HemoCleanse (which has a minority share interest in ZS Pharma), Fresenius Medical, Ash Access Technology (in which he has ownership interest), Renal Solutions, and DaVita RMS. He also is editor-in-chief of Seminars in Dialysis, ASKIN section.

ATLANTA – A novel first-in-class agent that selectively binds cations appears safe and effective for the treatment of hyperkalemia in patients with chronic kidney disease, according to findings from a phase II, dose-ranging proof-of-concept study.

Preliminary data from a phase III study of 753 patients, which was initiated based on the positive findings in the phase II study, similarly demonstrate the safety and efficacy of the selective monovalent cation trap known as ZS-9 (ZS Pharma), Dr. Stephen R. Ash reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

In 90 patients from the phase II study who were randomized to receive either placebo or one of three ZS-9 doses (0.3 g in 12 patients, 3 g in 24 patients, and 10 g in 24 patients), active treatment was associated with significantly greater dose-dependent reductions in serum potassium (K+) than was placebo, said Dr. Ash of Indiana University, Lafayette.

The mean serum K+ level at baseline for both the placebo group and the combined active treatment groups was 5.1 mEq/L. Within 48 hours of treatment initiation, 63% of patients in the 10-g ZS-9 group met the primary end point of at least a 1.0-mEq/L reduction in serum K+, compared with only 17% of patients in the placebo group.

The dose reduction in the 10-g group was "rapid and substantial," with a significant decrease, compared with placebo, occurring within 1 hour of the initial dose. Levels were 0.92-mEq/L lower than baseline after 38 hours (4 hours after the last dose), and 0.68-mEq/L lower than baseline at 48 hours (14 hours after the last dose). The levels remained significantly lower than placebo for an additional 3.5 days after the last dose, Dr. Ash said.

"At every point in the trial for these 10-g–dose patients, the serum potassium was lower in the treatment group than in the control group. ... At 38 hours, almost 90% of the patients who were on the 10-g dose had a serum potassium [level] of less than 4.5," he said.

Participants had mild to moderate chronic kidney disease with a glomerular filtration rate of 30-60 mL/min per 1.73 m², and mild to moderate hyperkalemia, with serum K+ levels of 5-6 mEq/L.

Treatment with the tasteless, odorless substance, which was delivered orally as a suspension in water three times daily at meal times, was well tolerated. No serious adverse events were reported, and no significant gastrointestinal issues, hypokalemia, hypomagnesemia, or hypocalcemia were observed.

Only one adverse event, a mild case of constipation in the 3-g–dose group, was thought to have a causal relationship to the study drug. No patients withdrew from the study.

The preliminary data from the pivotal randomized, controlled phase III trial also suggest a rapid and dose-dependent reduction in serum K+ in patients treated with ZS-9. In that study, patients were randomized to receive placebo or ZS-9 at doses of 1.25 g, 2.5 g, 5 g, or 10 g three times daily for the initial 48 hours.

Patients whose serum K+ levels normalized during that initial phase of treatment were then randomized to receive placebo or one of the four active drug doses administered daily for 12 days.

Patients in the phase III trial had serum K+ levels of 5-6.5 mEq/L. Those in the 2.5-g, 5-g, and 10-g groups met the primary endpoint, with significantly greater reductions in serum K+, compared with those on placebo, at 48 hours.

The mean serum K+ reduction was 0.73 mEq/L at the 10-g dose at 48 hours. The gastrointestinal adverse event rate was 5.1% in the placebo group patients, and 3.5% in the treatment group.

Final results from the phase III trial are expected in the coming months.

The findings are important because currently only one treatment – sodium polystyrene sulfonate (SPS), an organic polymer resin that nonselectively binds cations – is approved in the United States for the treatment of hyperkalemia – a serious condition that is associated with significant mortality and morbidity in patients with cardiovascular disease or chronic kidney disease.

"Even marginally high potassium levels, such as over 4.5, however, have an increased risk of death and ventricular fibrillation," Dr. Ash explained.

Further, hyperkalemia limits the ability to use cardioprotective and renoprotective agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, he said.

The efficacy of SPS for lowering serum K+ levels is questionable, and the agent has been associated with several serious adverse effects, including sodium loading, colonic necrosis, and other fatal gastrointestinal effects, Dr. Ash explained.

ZS-9 differs from traditional nonspecific and nonselective cation exchange organic polymer resins in that it is an inorganic cation exchanger – a result of advances in chemistry for the development of highly selective drug therapies.

"ZS-9 was designed and engineered to be highly selective for potassium," he said, noting that ZS-9 has more than nine times the potassium-binding ability of SPS, and is not systemically absorbed; thus, the risk of systemic toxicity is minimized or eliminated.

The findings thus far suggest that ZS-9 is a safe, reliable, fast, effective and well-tolerated therapy for lowering serum K+ levels in patients with hyperkalemia, Dr. Ash concluded.

Dr. Ash disclosed ties with Merit Medical, HemoCleanse (which has a minority share interest in ZS Pharma), Fresenius Medical, Ash Access Technology (in which he has ownership interest), Renal Solutions, and DaVita RMS. He also is editor-in-chief of Seminars in Dialysis, ASKIN section.

ATLANTA – A novel first-in-class agent that selectively binds cations appears safe and effective for the treatment of hyperkalemia in patients with chronic kidney disease, according to findings from a phase II, dose-ranging proof-of-concept study.

Preliminary data from a phase III study of 753 patients, which was initiated based on the positive findings in the phase II study, similarly demonstrate the safety and efficacy of the selective monovalent cation trap known as ZS-9 (ZS Pharma), Dr. Stephen R. Ash reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

In 90 patients from the phase II study who were randomized to receive either placebo or one of three ZS-9 doses (0.3 g in 12 patients, 3 g in 24 patients, and 10 g in 24 patients), active treatment was associated with significantly greater dose-dependent reductions in serum potassium (K+) than was placebo, said Dr. Ash of Indiana University, Lafayette.

The mean serum K+ level at baseline for both the placebo group and the combined active treatment groups was 5.1 mEq/L. Within 48 hours of treatment initiation, 63% of patients in the 10-g ZS-9 group met the primary end point of at least a 1.0-mEq/L reduction in serum K+, compared with only 17% of patients in the placebo group.

The dose reduction in the 10-g group was "rapid and substantial," with a significant decrease, compared with placebo, occurring within 1 hour of the initial dose. Levels were 0.92-mEq/L lower than baseline after 38 hours (4 hours after the last dose), and 0.68-mEq/L lower than baseline at 48 hours (14 hours after the last dose). The levels remained significantly lower than placebo for an additional 3.5 days after the last dose, Dr. Ash said.

"At every point in the trial for these 10-g–dose patients, the serum potassium was lower in the treatment group than in the control group. ... At 38 hours, almost 90% of the patients who were on the 10-g dose had a serum potassium [level] of less than 4.5," he said.

Participants had mild to moderate chronic kidney disease with a glomerular filtration rate of 30-60 mL/min per 1.73 m², and mild to moderate hyperkalemia, with serum K+ levels of 5-6 mEq/L.

Treatment with the tasteless, odorless substance, which was delivered orally as a suspension in water three times daily at meal times, was well tolerated. No serious adverse events were reported, and no significant gastrointestinal issues, hypokalemia, hypomagnesemia, or hypocalcemia were observed.

Only one adverse event, a mild case of constipation in the 3-g–dose group, was thought to have a causal relationship to the study drug. No patients withdrew from the study.

The preliminary data from the pivotal randomized, controlled phase III trial also suggest a rapid and dose-dependent reduction in serum K+ in patients treated with ZS-9. In that study, patients were randomized to receive placebo or ZS-9 at doses of 1.25 g, 2.5 g, 5 g, or 10 g three times daily for the initial 48 hours.

Patients whose serum K+ levels normalized during that initial phase of treatment were then randomized to receive placebo or one of the four active drug doses administered daily for 12 days.

Patients in the phase III trial had serum K+ levels of 5-6.5 mEq/L. Those in the 2.5-g, 5-g, and 10-g groups met the primary endpoint, with significantly greater reductions in serum K+, compared with those on placebo, at 48 hours.

The mean serum K+ reduction was 0.73 mEq/L at the 10-g dose at 48 hours. The gastrointestinal adverse event rate was 5.1% in the placebo group patients, and 3.5% in the treatment group.

Final results from the phase III trial are expected in the coming months.

The findings are important because currently only one treatment – sodium polystyrene sulfonate (SPS), an organic polymer resin that nonselectively binds cations – is approved in the United States for the treatment of hyperkalemia – a serious condition that is associated with significant mortality and morbidity in patients with cardiovascular disease or chronic kidney disease.

"Even marginally high potassium levels, such as over 4.5, however, have an increased risk of death and ventricular fibrillation," Dr. Ash explained.

Further, hyperkalemia limits the ability to use cardioprotective and renoprotective agents such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, he said.

The efficacy of SPS for lowering serum K+ levels is questionable, and the agent has been associated with several serious adverse effects, including sodium loading, colonic necrosis, and other fatal gastrointestinal effects, Dr. Ash explained.

ZS-9 differs from traditional nonspecific and nonselective cation exchange organic polymer resins in that it is an inorganic cation exchanger – a result of advances in chemistry for the development of highly selective drug therapies.

"ZS-9 was designed and engineered to be highly selective for potassium," he said, noting that ZS-9 has more than nine times the potassium-binding ability of SPS, and is not systemically absorbed; thus, the risk of systemic toxicity is minimized or eliminated.

The findings thus far suggest that ZS-9 is a safe, reliable, fast, effective and well-tolerated therapy for lowering serum K+ levels in patients with hyperkalemia, Dr. Ash concluded.

Dr. Ash disclosed ties with Merit Medical, HemoCleanse (which has a minority share interest in ZS Pharma), Fresenius Medical, Ash Access Technology (in which he has ownership interest), Renal Solutions, and DaVita RMS. He also is editor-in-chief of Seminars in Dialysis, ASKIN section.

ATLANTA – Extending the duration of initial prednisolone treatment from 2 months to 6 months while escalating the dose failed to reduce the incidence of frequently relapsing nephrotic syndrome in children in a randomized, open-label, noninferiority trial.

The time to relapse did not differ significantly among 255 children with an initial episode of steroid-sensitive nephrotic syndrome who presented to any of 91 participating hospitals in Japan and who were randomized to receive either 2 or 6 months of initial prednisolone treatment with cumulative doses of 2,240 mg/m² and 3,885 mg/m², respectively, followed by relapse prednisolone treatment per study protocol for a total of 24 months.

At 24 months, the frequently relapsing nephrotic syndrome (FRNS)-free rates were 56.2% and 50.8% in the groups, respectively (hazard ratio, 0.86), Norishige Yoshikawa, Ph.D., reported in a late-breaking poster at Kidney Week 2013.

The hazard ratio met the prespecified noninferiority margin (HR, 1.3), said Dr. Yoshikawa of the department of pediatrics at Wakayama Medical University, Japan.

Furthermore, the groups did not differ with respect to number of relapses: 1.25 per person-year in the 2-month group vs. 1.30 per person-year in the 6-month group, for a relapse rate ratio of 0.94.

The initial approach to treatment in children with FRNS varies considerably, and these findings conflict with those of a 2007 Cochrane Review (Cochrane Database Syst. Rev. 2007;4:CD001533 [doi: 10.1002/14651858.CD001533.pub4]). That review identified 24 related trials that suggested longer duration of prednisone or prednisolone treatment (3 or more months vs. 2 months) reduced the risk of relapse at 12-24 months (risk ratio, 0.70), that there was an inverse linear relationship between treatment duration and risk of relapse (RR, 1.26), and that 6 months (vs. 3 months) of treatment was more effective for reducing the risk of relapse (RR, 0.57).

Although the Cochrane Review authors concluded that children with a first episode of steroid-sensitive nephrotic syndrome should be treated for at least 3 months – and that there appears to be an increase in benefit with up to 7 months of treatment – they also noted that additional well-designed and adequately powered randomized clinical trials were needed to assess the appropriate duration of initial steroid treatment in children with FRNS, Dr. Yoshikawa said.

The meeting was sponsored by the American Society of Nephrology. Dr. Yoshikawa’s study was supported with non–U.S. government funding. Dr. Yoshikawa reported having no disclosures.

ATLANTA – Extending the duration of initial prednisolone treatment from 2 months to 6 months while escalating the dose failed to reduce the incidence of frequently relapsing nephrotic syndrome in children in a randomized, open-label, noninferiority trial.

The time to relapse did not differ significantly among 255 children with an initial episode of steroid-sensitive nephrotic syndrome who presented to any of 91 participating hospitals in Japan and who were randomized to receive either 2 or 6 months of initial prednisolone treatment with cumulative doses of 2,240 mg/m² and 3,885 mg/m², respectively, followed by relapse prednisolone treatment per study protocol for a total of 24 months.

At 24 months, the frequently relapsing nephrotic syndrome (FRNS)-free rates were 56.2% and 50.8% in the groups, respectively (hazard ratio, 0.86), Norishige Yoshikawa, Ph.D., reported in a late-breaking poster at Kidney Week 2013.

The hazard ratio met the prespecified noninferiority margin (HR, 1.3), said Dr. Yoshikawa of the department of pediatrics at Wakayama Medical University, Japan.

Furthermore, the groups did not differ with respect to number of relapses: 1.25 per person-year in the 2-month group vs. 1.30 per person-year in the 6-month group, for a relapse rate ratio of 0.94.

The initial approach to treatment in children with FRNS varies considerably, and these findings conflict with those of a 2007 Cochrane Review (Cochrane Database Syst. Rev. 2007;4:CD001533 [doi: 10.1002/14651858.CD001533.pub4]). That review identified 24 related trials that suggested longer duration of prednisone or prednisolone treatment (3 or more months vs. 2 months) reduced the risk of relapse at 12-24 months (risk ratio, 0.70), that there was an inverse linear relationship between treatment duration and risk of relapse (RR, 1.26), and that 6 months (vs. 3 months) of treatment was more effective for reducing the risk of relapse (RR, 0.57).

Although the Cochrane Review authors concluded that children with a first episode of steroid-sensitive nephrotic syndrome should be treated for at least 3 months – and that there appears to be an increase in benefit with up to 7 months of treatment – they also noted that additional well-designed and adequately powered randomized clinical trials were needed to assess the appropriate duration of initial steroid treatment in children with FRNS, Dr. Yoshikawa said.

The meeting was sponsored by the American Society of Nephrology. Dr. Yoshikawa’s study was supported with non–U.S. government funding. Dr. Yoshikawa reported having no disclosures.

ATLANTA – Extending the duration of initial prednisolone treatment from 2 months to 6 months while escalating the dose failed to reduce the incidence of frequently relapsing nephrotic syndrome in children in a randomized, open-label, noninferiority trial.

The time to relapse did not differ significantly among 255 children with an initial episode of steroid-sensitive nephrotic syndrome who presented to any of 91 participating hospitals in Japan and who were randomized to receive either 2 or 6 months of initial prednisolone treatment with cumulative doses of 2,240 mg/m² and 3,885 mg/m², respectively, followed by relapse prednisolone treatment per study protocol for a total of 24 months.

At 24 months, the frequently relapsing nephrotic syndrome (FRNS)-free rates were 56.2% and 50.8% in the groups, respectively (hazard ratio, 0.86), Norishige Yoshikawa, Ph.D., reported in a late-breaking poster at Kidney Week 2013.

The hazard ratio met the prespecified noninferiority margin (HR, 1.3), said Dr. Yoshikawa of the department of pediatrics at Wakayama Medical University, Japan.

Furthermore, the groups did not differ with respect to number of relapses: 1.25 per person-year in the 2-month group vs. 1.30 per person-year in the 6-month group, for a relapse rate ratio of 0.94.

The initial approach to treatment in children with FRNS varies considerably, and these findings conflict with those of a 2007 Cochrane Review (Cochrane Database Syst. Rev. 2007;4:CD001533 [doi: 10.1002/14651858.CD001533.pub4]). That review identified 24 related trials that suggested longer duration of prednisone or prednisolone treatment (3 or more months vs. 2 months) reduced the risk of relapse at 12-24 months (risk ratio, 0.70), that there was an inverse linear relationship between treatment duration and risk of relapse (RR, 1.26), and that 6 months (vs. 3 months) of treatment was more effective for reducing the risk of relapse (RR, 0.57).

Although the Cochrane Review authors concluded that children with a first episode of steroid-sensitive nephrotic syndrome should be treated for at least 3 months – and that there appears to be an increase in benefit with up to 7 months of treatment – they also noted that additional well-designed and adequately powered randomized clinical trials were needed to assess the appropriate duration of initial steroid treatment in children with FRNS, Dr. Yoshikawa said.

The meeting was sponsored by the American Society of Nephrology. Dr. Yoshikawa’s study was supported with non–U.S. government funding. Dr. Yoshikawa reported having no disclosures.

ATLANTA – Variants in the gene encoding apolipoprotein L1 are associated with a nearly twofold increased risk of chronic kidney disease progression in African American patients, according to an analysis of data from the Chronic Renal Insufficiency Cohort and the African American Study of Kidney Disease and Hypertension.

In addition, kidney function is lost at double the rate in patients with the apolipoprotein L1 (APOL1) renal risk variants.

The findings – which persisted regardless of chronic kidney disease (CKD) etiology and well-controlled blood pressure – may explain, in part, the markedly increased risk of end-stage renal disease (ESRD) in African American patients, compared with European American patients, Dr. Afshin Parsa of the University of Maryland, Baltimore, reported at Kidney Week 2013.

The findings were published simultaneously online Nov. 9 in the New England Journal of Medicine (2013 Nov. 9 [doi:10.1056/NEJMoa1310345]), and will appear in the Dec. 5 print issue.

In the CRIC (Chronic Renal Insufficiency Cohort) study, 2,955 patients with CKD, nearly half of whom (46%) had diabetes, were evaluated based on whether they had zero or one copy of the APOL1 variants (low-risk group) or two copies of the variants (high-risk group). The primary outcomes in that cohort were the slope in the estimated glomerular filtration rate (eGFR), and the composite of ESRD, or a reduction of 50% in the eGFR from baseline, said Dr. Parsa, who was one of the CRIC investigators.

Among black patients in the high-risk group, the decline in eGFR was significantly more rapid and the rate of the composite renal outcome significantly higher than in white patients in that group, regardless of diabetes status. The rate of decline was similar among black and white patients in the low-risk group.

Among African American patients with diabetes in the low-risk group, white patients with diabetes, and African American patients with diabetes in the high-risk group, the eGFR slopes were –2.7, –1.5, and –4.3 mL/min per 1.73 m² per year, respectively. Among those without diabetes, the corresponding slopes were –0.7, –1.0, and –2.9.

The adjusted hazard ratios for a renal event were 1.95 and 1.40 for African American patients, compared with white patients in the high-risk and low-risk groups with diabetes, respectively. The corresponding hazard ratios among those without diabetes were 2.68 and 1.57. The adjusted hazard ratio for the composite renal outcome was 1.61 for African American patients in the high-risk vs. the low-risk groups.

In the AASK (African American Study of Kidney Disease and Hypertension) study, 693 African American patients with hypertension-related chronic kidney disease and without diabetes were evaluated, and the primary outcome measure was a composite of end-stage renal disease or a doubling of the serum creatinine level.

The primary outcome occurred in 58.1% of those in the high risk group, compared with 36.6% of those in the low-risk group (hazard ratio, 1.88). No interactions between APOL1 status and trial interventions or the presence of baseline proteinuria were seen in AASK, Dr. Parsa said during a press briefing at the conference, which was sponsored by the American Society of Nephrology.

Also, the effect of APOL1 on CKD progression was not confounded by blood pressure levels, he noted.

The findings of the current analysis build on those from landmark 2008 research that led to identification of the APOL1 gene variants as a risk factor for kidney disease not associated with diabetes, he said, adding that the current findings are the first to provide direct evidence that the APOL1 high-risk variants are associated with increased disease progression over time.

This could potentially lead to genotyping of African Americans to assess their risk for disease progression, and could also lead to new treatment strategies for slowing the progression of CKD, the investigators said, noting that such strategies are currently limited.

The findings do not, however, fully explain the well-documented racial disparities in ESRD. In the United States, African Americans patients have about twice the risk of ESRD as do white patients, even after accounting for differences in socioeconomic and clinical risk factors.

The study results highlight the need to identify other risk factors that can account for residual disparities in end-stage renal disease between African American and white patients, they concluded.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Parsa reported having no disclosures.

ATLANTA – Variants in the gene encoding apolipoprotein L1 are associated with a nearly twofold increased risk of chronic kidney disease progression in African American patients, according to an analysis of data from the Chronic Renal Insufficiency Cohort and the African American Study of Kidney Disease and Hypertension.

In addition, kidney function is lost at double the rate in patients with the apolipoprotein L1 (APOL1) renal risk variants.

The findings – which persisted regardless of chronic kidney disease (CKD) etiology and well-controlled blood pressure – may explain, in part, the markedly increased risk of end-stage renal disease (ESRD) in African American patients, compared with European American patients, Dr. Afshin Parsa of the University of Maryland, Baltimore, reported at Kidney Week 2013.

The findings were published simultaneously online Nov. 9 in the New England Journal of Medicine (2013 Nov. 9 [doi:10.1056/NEJMoa1310345]), and will appear in the Dec. 5 print issue.

In the CRIC (Chronic Renal Insufficiency Cohort) study, 2,955 patients with CKD, nearly half of whom (46%) had diabetes, were evaluated based on whether they had zero or one copy of the APOL1 variants (low-risk group) or two copies of the variants (high-risk group). The primary outcomes in that cohort were the slope in the estimated glomerular filtration rate (eGFR), and the composite of ESRD, or a reduction of 50% in the eGFR from baseline, said Dr. Parsa, who was one of the CRIC investigators.

Among black patients in the high-risk group, the decline in eGFR was significantly more rapid and the rate of the composite renal outcome significantly higher than in white patients in that group, regardless of diabetes status. The rate of decline was similar among black and white patients in the low-risk group.

Among African American patients with diabetes in the low-risk group, white patients with diabetes, and African American patients with diabetes in the high-risk group, the eGFR slopes were –2.7, –1.5, and –4.3 mL/min per 1.73 m² per year, respectively. Among those without diabetes, the corresponding slopes were –0.7, –1.0, and –2.9.

The adjusted hazard ratios for a renal event were 1.95 and 1.40 for African American patients, compared with white patients in the high-risk and low-risk groups with diabetes, respectively. The corresponding hazard ratios among those without diabetes were 2.68 and 1.57. The adjusted hazard ratio for the composite renal outcome was 1.61 for African American patients in the high-risk vs. the low-risk groups.

In the AASK (African American Study of Kidney Disease and Hypertension) study, 693 African American patients with hypertension-related chronic kidney disease and without diabetes were evaluated, and the primary outcome measure was a composite of end-stage renal disease or a doubling of the serum creatinine level.

The primary outcome occurred in 58.1% of those in the high risk group, compared with 36.6% of those in the low-risk group (hazard ratio, 1.88). No interactions between APOL1 status and trial interventions or the presence of baseline proteinuria were seen in AASK, Dr. Parsa said during a press briefing at the conference, which was sponsored by the American Society of Nephrology.

Also, the effect of APOL1 on CKD progression was not confounded by blood pressure levels, he noted.

The findings of the current analysis build on those from landmark 2008 research that led to identification of the APOL1 gene variants as a risk factor for kidney disease not associated with diabetes, he said, adding that the current findings are the first to provide direct evidence that the APOL1 high-risk variants are associated with increased disease progression over time.

This could potentially lead to genotyping of African Americans to assess their risk for disease progression, and could also lead to new treatment strategies for slowing the progression of CKD, the investigators said, noting that such strategies are currently limited.

The findings do not, however, fully explain the well-documented racial disparities in ESRD. In the United States, African Americans patients have about twice the risk of ESRD as do white patients, even after accounting for differences in socioeconomic and clinical risk factors.

The study results highlight the need to identify other risk factors that can account for residual disparities in end-stage renal disease between African American and white patients, they concluded.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Parsa reported having no disclosures.

ATLANTA – Variants in the gene encoding apolipoprotein L1 are associated with a nearly twofold increased risk of chronic kidney disease progression in African American patients, according to an analysis of data from the Chronic Renal Insufficiency Cohort and the African American Study of Kidney Disease and Hypertension.

In addition, kidney function is lost at double the rate in patients with the apolipoprotein L1 (APOL1) renal risk variants.

The findings – which persisted regardless of chronic kidney disease (CKD) etiology and well-controlled blood pressure – may explain, in part, the markedly increased risk of end-stage renal disease (ESRD) in African American patients, compared with European American patients, Dr. Afshin Parsa of the University of Maryland, Baltimore, reported at Kidney Week 2013.

The findings were published simultaneously online Nov. 9 in the New England Journal of Medicine (2013 Nov. 9 [doi:10.1056/NEJMoa1310345]), and will appear in the Dec. 5 print issue.

In the CRIC (Chronic Renal Insufficiency Cohort) study, 2,955 patients with CKD, nearly half of whom (46%) had diabetes, were evaluated based on whether they had zero or one copy of the APOL1 variants (low-risk group) or two copies of the variants (high-risk group). The primary outcomes in that cohort were the slope in the estimated glomerular filtration rate (eGFR), and the composite of ESRD, or a reduction of 50% in the eGFR from baseline, said Dr. Parsa, who was one of the CRIC investigators.

Among black patients in the high-risk group, the decline in eGFR was significantly more rapid and the rate of the composite renal outcome significantly higher than in white patients in that group, regardless of diabetes status. The rate of decline was similar among black and white patients in the low-risk group.

Among African American patients with diabetes in the low-risk group, white patients with diabetes, and African American patients with diabetes in the high-risk group, the eGFR slopes were –2.7, –1.5, and –4.3 mL/min per 1.73 m² per year, respectively. Among those without diabetes, the corresponding slopes were –0.7, –1.0, and –2.9.

The adjusted hazard ratios for a renal event were 1.95 and 1.40 for African American patients, compared with white patients in the high-risk and low-risk groups with diabetes, respectively. The corresponding hazard ratios among those without diabetes were 2.68 and 1.57. The adjusted hazard ratio for the composite renal outcome was 1.61 for African American patients in the high-risk vs. the low-risk groups.

In the AASK (African American Study of Kidney Disease and Hypertension) study, 693 African American patients with hypertension-related chronic kidney disease and without diabetes were evaluated, and the primary outcome measure was a composite of end-stage renal disease or a doubling of the serum creatinine level.

The primary outcome occurred in 58.1% of those in the high risk group, compared with 36.6% of those in the low-risk group (hazard ratio, 1.88). No interactions between APOL1 status and trial interventions or the presence of baseline proteinuria were seen in AASK, Dr. Parsa said during a press briefing at the conference, which was sponsored by the American Society of Nephrology.

Also, the effect of APOL1 on CKD progression was not confounded by blood pressure levels, he noted.

The findings of the current analysis build on those from landmark 2008 research that led to identification of the APOL1 gene variants as a risk factor for kidney disease not associated with diabetes, he said, adding that the current findings are the first to provide direct evidence that the APOL1 high-risk variants are associated with increased disease progression over time.

This could potentially lead to genotyping of African Americans to assess their risk for disease progression, and could also lead to new treatment strategies for slowing the progression of CKD, the investigators said, noting that such strategies are currently limited.

The findings do not, however, fully explain the well-documented racial disparities in ESRD. In the United States, African Americans patients have about twice the risk of ESRD as do white patients, even after accounting for differences in socioeconomic and clinical risk factors.

The study results highlight the need to identify other risk factors that can account for residual disparities in end-stage renal disease between African American and white patients, they concluded.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Parsa reported having no disclosures.

ATLANTA – A novel, low-resource bedside diagnostic tool that measures saliva urea nitrogen appears useful for identifying patients with advanced acute kidney injury who have an increased likelihood of requiring dialysis.

In a study involving 44 patients, the tool – a dipstick that measures saliva urea nitrogen (SUN), a marker of kidney function – reliably discriminated Acute Kidney Injury Network (AKIN) stage 3 AKI from earlier AKI stages, Dr. Roberto Picoits-Filho reported at Kidney Week 2013.

SUN, as measured using the dipstick, was significantly correlated with blood urea nitrogen, or BUN (R_s = 0.77), irrespective of AKIN stage or AKI etiology, Dr. Picoits-Filho reported during a press briefing at the conference, which was sponsored by the American Society of Nephrology

The diagnostic performances of the tests were comparable: For SUN, the area under the curve of a receiver operating characteristic curve (AUC ROC) was 0.76, and for BUN the value was 0.69, he said.

"We saw that the test was actually very good, particularly in patients with very severe stages of kidney injury, which is important, because those are the patients who most likely will need to go into dialysis or more complex treatment," said Dr. Picoits-Filho of the Pro-rim Foundation and Pontifícia Universidade Católica do Parana, Curitiba, Brazil.

Patients included in the study were adults (mean age, 59.5 years; 58% women) who were hospitalized with prerenal (67%), renal (24%), or postrenal (9%) suspected AKI. A third had AKIN stage 1 disease, 27% had stage 2 disease, and 40% had stage 3 disease.

Unstimulated saliva was applied to the dipstick to measure whether SUN concentrations were 5-14, 15-24, 25-34, 35-54, 55-74, or 75 or greater mg/dL; BUN was measured concomitantly.

The findings are notable because while AKI in the intensive care unit setting is usually due to acute tubular necrosis, a large proportion of AKI cases outside of the ICU are due to prerenal AKI, which is reversible if diagnosed early and treated aggressively, Dr. Picoits-Filho said.

One way of detecting AKI early on in both the hospital and outpatient settings is by criteria defined by recent consensus: "basically by glomerular filtration rate, but also by urine output," he said.

By using serum creatinine to estimate GFR, you can actually detect patients with AKI. This defines risk for developing more severe AKI (and can help in preventing the need for renal replacement therapy), and also predicts in-hospital mortality, he said.

"The problem is that you need a laboratory facility to get this measurement, and this is not always available, especially in remote areas of the world," he added.

The current findings suggest the SUN dipstick could improve the diagnosis of advanced AKI and aid in triaging patients – particularly in remote areas with limited access to clinical chemistry facilities – and may improve outcomes, he said.

While the test did not prove efficient as a screening tool for chronic kidney disease, it could potentially have a role in monitoring those with chronic kidney disease, he noted.

This study was supported by the Renal Research Institute, New York, and the International Society of Nephrology. Dr. Picoits-Filho reported having no other disclosures.

ATLANTA – A novel, low-resource bedside diagnostic tool that measures saliva urea nitrogen appears useful for identifying patients with advanced acute kidney injury who have an increased likelihood of requiring dialysis.

In a study involving 44 patients, the tool – a dipstick that measures saliva urea nitrogen (SUN), a marker of kidney function – reliably discriminated Acute Kidney Injury Network (AKIN) stage 3 AKI from earlier AKI stages, Dr. Roberto Picoits-Filho reported at Kidney Week 2013.

SUN, as measured using the dipstick, was significantly correlated with blood urea nitrogen, or BUN (R_s = 0.77), irrespective of AKIN stage or AKI etiology, Dr. Picoits-Filho reported during a press briefing at the conference, which was sponsored by the American Society of Nephrology

The diagnostic performances of the tests were comparable: For SUN, the area under the curve of a receiver operating characteristic curve (AUC ROC) was 0.76, and for BUN the value was 0.69, he said.

"We saw that the test was actually very good, particularly in patients with very severe stages of kidney injury, which is important, because those are the patients who most likely will need to go into dialysis or more complex treatment," said Dr. Picoits-Filho of the Pro-rim Foundation and Pontifícia Universidade Católica do Parana, Curitiba, Brazil.

Patients included in the study were adults (mean age, 59.5 years; 58% women) who were hospitalized with prerenal (67%), renal (24%), or postrenal (9%) suspected AKI. A third had AKIN stage 1 disease, 27% had stage 2 disease, and 40% had stage 3 disease.

Unstimulated saliva was applied to the dipstick to measure whether SUN concentrations were 5-14, 15-24, 25-34, 35-54, 55-74, or 75 or greater mg/dL; BUN was measured concomitantly.

The findings are notable because while AKI in the intensive care unit setting is usually due to acute tubular necrosis, a large proportion of AKI cases outside of the ICU are due to prerenal AKI, which is reversible if diagnosed early and treated aggressively, Dr. Picoits-Filho said.

One way of detecting AKI early on in both the hospital and outpatient settings is by criteria defined by recent consensus: "basically by glomerular filtration rate, but also by urine output," he said.

By using serum creatinine to estimate GFR, you can actually detect patients with AKI. This defines risk for developing more severe AKI (and can help in preventing the need for renal replacement therapy), and also predicts in-hospital mortality, he said.

"The problem is that you need a laboratory facility to get this measurement, and this is not always available, especially in remote areas of the world," he added.

The current findings suggest the SUN dipstick could improve the diagnosis of advanced AKI and aid in triaging patients – particularly in remote areas with limited access to clinical chemistry facilities – and may improve outcomes, he said.

While the test did not prove efficient as a screening tool for chronic kidney disease, it could potentially have a role in monitoring those with chronic kidney disease, he noted.

This study was supported by the Renal Research Institute, New York, and the International Society of Nephrology. Dr. Picoits-Filho reported having no other disclosures.

ATLANTA – A novel, low-resource bedside diagnostic tool that measures saliva urea nitrogen appears useful for identifying patients with advanced acute kidney injury who have an increased likelihood of requiring dialysis.

In a study involving 44 patients, the tool – a dipstick that measures saliva urea nitrogen (SUN), a marker of kidney function – reliably discriminated Acute Kidney Injury Network (AKIN) stage 3 AKI from earlier AKI stages, Dr. Roberto Picoits-Filho reported at Kidney Week 2013.

SUN, as measured using the dipstick, was significantly correlated with blood urea nitrogen, or BUN (R_s = 0.77), irrespective of AKIN stage or AKI etiology, Dr. Picoits-Filho reported during a press briefing at the conference, which was sponsored by the American Society of Nephrology

The diagnostic performances of the tests were comparable: For SUN, the area under the curve of a receiver operating characteristic curve (AUC ROC) was 0.76, and for BUN the value was 0.69, he said.

"We saw that the test was actually very good, particularly in patients with very severe stages of kidney injury, which is important, because those are the patients who most likely will need to go into dialysis or more complex treatment," said Dr. Picoits-Filho of the Pro-rim Foundation and Pontifícia Universidade Católica do Parana, Curitiba, Brazil.

Patients included in the study were adults (mean age, 59.5 years; 58% women) who were hospitalized with prerenal (67%), renal (24%), or postrenal (9%) suspected AKI. A third had AKIN stage 1 disease, 27% had stage 2 disease, and 40% had stage 3 disease.

Unstimulated saliva was applied to the dipstick to measure whether SUN concentrations were 5-14, 15-24, 25-34, 35-54, 55-74, or 75 or greater mg/dL; BUN was measured concomitantly.

The findings are notable because while AKI in the intensive care unit setting is usually due to acute tubular necrosis, a large proportion of AKI cases outside of the ICU are due to prerenal AKI, which is reversible if diagnosed early and treated aggressively, Dr. Picoits-Filho said.

One way of detecting AKI early on in both the hospital and outpatient settings is by criteria defined by recent consensus: "basically by glomerular filtration rate, but also by urine output," he said.

By using serum creatinine to estimate GFR, you can actually detect patients with AKI. This defines risk for developing more severe AKI (and can help in preventing the need for renal replacement therapy), and also predicts in-hospital mortality, he said.

"The problem is that you need a laboratory facility to get this measurement, and this is not always available, especially in remote areas of the world," he added.

The current findings suggest the SUN dipstick could improve the diagnosis of advanced AKI and aid in triaging patients – particularly in remote areas with limited access to clinical chemistry facilities – and may improve outcomes, he said.

While the test did not prove efficient as a screening tool for chronic kidney disease, it could potentially have a role in monitoring those with chronic kidney disease, he noted.

This study was supported by the Renal Research Institute, New York, and the International Society of Nephrology. Dr. Picoits-Filho reported having no other disclosures.

ATLANTA – Mindfulness meditation may improve blood pressure in hypertensive patients with chronic kidney disease, according to findings from a small randomized study.

This study involved 15 patients who had stage 3 chronic kidney disease and hypertension. Compared with a control condition involving blood pressure education, mindfulness meditation was associated with significantly greater reductions in systolic blood pressure (–10.2 vs. –0.8 mm Hg), diastolic blood pressure (–6.4 vs. –1.8 mm Hg), and mean arterial pressure (–7.7 vs. –1.4 mm Hg), Dr. Jeanie Park reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

©Jupiterimages

Mindfulness meditation – a "type of meditation that is focused on awareness of sensations of the present moment without any type of cognitive elaboration of those sensations, without judgment, without trying to modify those sensations" – also was associated with a significantly greater reduction in muscle sympathetic nerve activity as measured using microneurography (–10.7 vs. 1.9 bursts/min), said Dr. Park of Emory University, Atlanta.

Study participants were male veterans who completed two study visits, undergoing – in randomized crossover fashion – 14 minutes of guided mindfulness meditation at one visit, and 14 minutes of a control condition involving blood pressure education at one visit.

Because a lower breathing rate was observed during mindfulness meditation, a subset of the patients completed a third visit in which they used controlled breathing as a second control measure. During this visit, they lowered their breathing rate to the same rate achieved during mindfulness meditation.

"What we saw was that during mindfulness meditation, there was a significant reduction in sympathetic nerve activity compared with the control, but during controlled breathing ... there was no difference in sympathetic activity. This suggests that slow breathing by itself is not sufficient to lower blood pressure and sympathetic activity, and that there is something unique about mindfulness meditation that might be modulating sympathetic activity and blood pressure in our patients," Dr. Park said.

Although mindfulness meditation has been shown in prior studies to have "modest but meaningful" effects in patients with high blood pressure, the current findings are among the first to demonstrate an association between mindfulness meditation and decreased blood pressure in hypertensive patients with chronic kidney disease. The effect appeared to be mediated by an acute reduction in sympathetic nervous system activity, Dr. Park said.

Chronic kidney disease is characterized by chronic sympathetic nervous system overactivity, which contributes to hypertension and mortality, she explained.

"In clinical practice, we aim to counteract sympathetic activity to lower blood pressure. We do this using antihypertensive medications such as beta-blockers and [clonazepam], but the problem with these medications is that oftentimes their use is limited due to their side effects ... so there certainly is a need to investigate alternative or additive therapies to counteract sympathetic activity and lower blood pressure in our patient group," she said.

The findings of this study suggest that mindfulness meditation may have real physiological effects on autonomic control, and may prove useful as a complementary therapy in chronic kidney disease patients, she concluded, noting that future studies are needed to determine whether long-term reductions in blood pressure can be achieved by using mindfulness meditation.

Dr. Park reported having no disclosures.

ATLANTA – Mindfulness meditation may improve blood pressure in hypertensive patients with chronic kidney disease, according to findings from a small randomized study.

This study involved 15 patients who had stage 3 chronic kidney disease and hypertension. Compared with a control condition involving blood pressure education, mindfulness meditation was associated with significantly greater reductions in systolic blood pressure (–10.2 vs. –0.8 mm Hg), diastolic blood pressure (–6.4 vs. –1.8 mm Hg), and mean arterial pressure (–7.7 vs. –1.4 mm Hg), Dr. Jeanie Park reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

©Jupiterimages

Mindfulness meditation – a "type of meditation that is focused on awareness of sensations of the present moment without any type of cognitive elaboration of those sensations, without judgment, without trying to modify those sensations" – also was associated with a significantly greater reduction in muscle sympathetic nerve activity as measured using microneurography (–10.7 vs. 1.9 bursts/min), said Dr. Park of Emory University, Atlanta.

Study participants were male veterans who completed two study visits, undergoing – in randomized crossover fashion – 14 minutes of guided mindfulness meditation at one visit, and 14 minutes of a control condition involving blood pressure education at one visit.

Because a lower breathing rate was observed during mindfulness meditation, a subset of the patients completed a third visit in which they used controlled breathing as a second control measure. During this visit, they lowered their breathing rate to the same rate achieved during mindfulness meditation.

"What we saw was that during mindfulness meditation, there was a significant reduction in sympathetic nerve activity compared with the control, but during controlled breathing ... there was no difference in sympathetic activity. This suggests that slow breathing by itself is not sufficient to lower blood pressure and sympathetic activity, and that there is something unique about mindfulness meditation that might be modulating sympathetic activity and blood pressure in our patients," Dr. Park said.

Although mindfulness meditation has been shown in prior studies to have "modest but meaningful" effects in patients with high blood pressure, the current findings are among the first to demonstrate an association between mindfulness meditation and decreased blood pressure in hypertensive patients with chronic kidney disease. The effect appeared to be mediated by an acute reduction in sympathetic nervous system activity, Dr. Park said.

Chronic kidney disease is characterized by chronic sympathetic nervous system overactivity, which contributes to hypertension and mortality, she explained.

"In clinical practice, we aim to counteract sympathetic activity to lower blood pressure. We do this using antihypertensive medications such as beta-blockers and [clonazepam], but the problem with these medications is that oftentimes their use is limited due to their side effects ... so there certainly is a need to investigate alternative or additive therapies to counteract sympathetic activity and lower blood pressure in our patient group," she said.

The findings of this study suggest that mindfulness meditation may have real physiological effects on autonomic control, and may prove useful as a complementary therapy in chronic kidney disease patients, she concluded, noting that future studies are needed to determine whether long-term reductions in blood pressure can be achieved by using mindfulness meditation.

Dr. Park reported having no disclosures.

ATLANTA – Mindfulness meditation may improve blood pressure in hypertensive patients with chronic kidney disease, according to findings from a small randomized study.

This study involved 15 patients who had stage 3 chronic kidney disease and hypertension. Compared with a control condition involving blood pressure education, mindfulness meditation was associated with significantly greater reductions in systolic blood pressure (–10.2 vs. –0.8 mm Hg), diastolic blood pressure (–6.4 vs. –1.8 mm Hg), and mean arterial pressure (–7.7 vs. –1.4 mm Hg), Dr. Jeanie Park reported at Kidney Week 2013, sponsored by the American Society of Nephrology.

©Jupiterimages

Mindfulness meditation – a "type of meditation that is focused on awareness of sensations of the present moment without any type of cognitive elaboration of those sensations, without judgment, without trying to modify those sensations" – also was associated with a significantly greater reduction in muscle sympathetic nerve activity as measured using microneurography (–10.7 vs. 1.9 bursts/min), said Dr. Park of Emory University, Atlanta.

Study participants were male veterans who completed two study visits, undergoing – in randomized crossover fashion – 14 minutes of guided mindfulness meditation at one visit, and 14 minutes of a control condition involving blood pressure education at one visit.

Because a lower breathing rate was observed during mindfulness meditation, a subset of the patients completed a third visit in which they used controlled breathing as a second control measure. During this visit, they lowered their breathing rate to the same rate achieved during mindfulness meditation.

"What we saw was that during mindfulness meditation, there was a significant reduction in sympathetic nerve activity compared with the control, but during controlled breathing ... there was no difference in sympathetic activity. This suggests that slow breathing by itself is not sufficient to lower blood pressure and sympathetic activity, and that there is something unique about mindfulness meditation that might be modulating sympathetic activity and blood pressure in our patients," Dr. Park said.

Although mindfulness meditation has been shown in prior studies to have "modest but meaningful" effects in patients with high blood pressure, the current findings are among the first to demonstrate an association between mindfulness meditation and decreased blood pressure in hypertensive patients with chronic kidney disease. The effect appeared to be mediated by an acute reduction in sympathetic nervous system activity, Dr. Park said.

Chronic kidney disease is characterized by chronic sympathetic nervous system overactivity, which contributes to hypertension and mortality, she explained.

"In clinical practice, we aim to counteract sympathetic activity to lower blood pressure. We do this using antihypertensive medications such as beta-blockers and [clonazepam], but the problem with these medications is that oftentimes their use is limited due to their side effects ... so there certainly is a need to investigate alternative or additive therapies to counteract sympathetic activity and lower blood pressure in our patient group," she said.

The findings of this study suggest that mindfulness meditation may have real physiological effects on autonomic control, and may prove useful as a complementary therapy in chronic kidney disease patients, she concluded, noting that future studies are needed to determine whether long-term reductions in blood pressure can be achieved by using mindfulness meditation.

Dr. Park reported having no disclosures.

ATLANTA – Adding abatacept to low-dose intravenous cyclophosphamide did not improve the rate of complete renal response at 1 year, compared with IV cyclophosphamide alone, in patients with class III or IV lupus nephritis in the randomized, controlled ACCESS Trial.

The phase II findings suggested, however, that abatacept reduced the need for maintenance immunosuppression, and they also demonstrated for the first time that low-dose IV cyclophosphamide may have applicability in racially and ethnically diverse patients with lupus nephritis, Dr. Brad H. Rovin reported at Kidney Week 2013.

The overall complete renal response rates were similar at 33% and 31%, respectively, in 134 patients with class III or IV lupus nephritis who were enrolled in the trial, treated with a steroid taper and 500 mg of IV cyclophosphamide every 2 weeks for 6 weeks followed by 2 mg/kg of azathioprine daily. Patients then were randomized to receive abatacept or placebo at week 0, 2, and 4 and then monthly.

Complete plus partial responses occurred in 59% of patients in each arm, Dr. Rovin said at the conference, which was sponsored by the American Society of Nephrology.

Patients in the study had a urine protein-to-creatinine ratio (UPCR) greater than 1. Complete renal response was defined as a UPCR of less than 0.5, serum creatinine at normal or within 25% of baseline, and prednisone dose tapered to 10 mg daily or less. African Americans comprised 39% of the cohort, and Hispanic/Mestizo patients comprised 40%.

Among the African American patients, 33% in the treatment group, compared with 16% in the placebo group, achieved complete renal response. This difference was not statistically significant.

This finding is important, because while low-dose cyclophosphamide – the "Euro-Lupus regimen" – has been shown to be as effective as standard and more toxic higher dosing, studies had primarily included a European Caucasian population. It was unclear whether the low-dose regimen would be as effective in a multiracial and multiethnic population, said Dr. Rovin of Ohio State University Medical Center.

No differences were seen between the treatment and control groups with respect to anti-dsDNA or complement levels and/or the frequency of serious or infectious adverse events or study withdrawals.

Of note, azathioprine was stopped in treatment group patients who achieved complete renal response – but not control group patients who achieved complete renal response. These patients were followed to 52 weeks. At that time, 50% and 62% of the treatment group and control group patients, respectively, who were complete responders at 24 weeks still met the criteria for complete response, Dr. Rovin said.

While abatacept did not increase complete response rates, the treatment was associated with maintenance of complete renal response to 1 year despite discontinuation of maintenance immunosuppression in the treated patients and continued azathioprine treatment in the control group. This suggests that abatacept may reduce the need for maintenance immunosuppression, he said.

While it was disappointing that the addition of abatacept to background induction therapy with low-dose IV cyclophosphamide and corticosteroids did not improve the complete renal response rate in this study – despite murine models suggesting that the use of abatacept and IV cyclophosphamide act synergistically to arrest lupus nephritis progression – the findings offer two very important lessons for clinical practice, he said.

"We can take the low-dose cyclophosphamide regimen and potentially use that with good results in our [multiethnic, multiracial] patient population that we see here in this country, and I think that’s a huge step forward. It gives us another option to use besides mycophenolate mofetil and high-dose cyclophosphamide," he said, adding that the low-dose IV cyclophosphamide regimen is well tolerated and delivers a total dose of only 3 g of the drug – a dose that generally does not predispose to premature ovarian failure.

This is particularly important, because women of childbearing years comprise a majority of the patient population with lupus nephritis, he explained.

"We know from the Euro-Lupus trial that the low-dose regimen, over 10 years, provided the same maintenance of renal function as the high-dose regimen, so we have very good long-term follow-up. We don’t quite have that yet with mycophenolate mofetil, so I think that for those of us who are very frequent users of cyclophosphamide, this is a very good alternative to the high-dose, highly toxic regimen that has for so long been the standard of care," he said.

This study was funded by the National Institute of Allergy and Infectious Diseases via the Immune Tolerance Network. Bristol Myers Squibb provided the study drug. Dr. Rovin reported ties to Genentech, Questcor, TEVA, Biogen-IDEC, HGS, Johnson & Johnson, Roche, BMS, and TG Therapeutics.

ATLANTA – Adding abatacept to low-dose intravenous cyclophosphamide did not improve the rate of complete renal response at 1 year, compared with IV cyclophosphamide alone, in patients with class III or IV lupus nephritis in the randomized, controlled ACCESS Trial.

The phase II findings suggested, however, that abatacept reduced the need for maintenance immunosuppression, and they also demonstrated for the first time that low-dose IV cyclophosphamide may have applicability in racially and ethnically diverse patients with lupus nephritis, Dr. Brad H. Rovin reported at Kidney Week 2013.

The overall complete renal response rates were similar at 33% and 31%, respectively, in 134 patients with class III or IV lupus nephritis who were enrolled in the trial, treated with a steroid taper and 500 mg of IV cyclophosphamide every 2 weeks for 6 weeks followed by 2 mg/kg of azathioprine daily. Patients then were randomized to receive abatacept or placebo at week 0, 2, and 4 and then monthly.

Complete plus partial responses occurred in 59% of patients in each arm, Dr. Rovin said at the conference, which was sponsored by the American Society of Nephrology.

Patients in the study had a urine protein-to-creatinine ratio (UPCR) greater than 1. Complete renal response was defined as a UPCR of less than 0.5, serum creatinine at normal or within 25% of baseline, and prednisone dose tapered to 10 mg daily or less. African Americans comprised 39% of the cohort, and Hispanic/Mestizo patients comprised 40%.

Among the African American patients, 33% in the treatment group, compared with 16% in the placebo group, achieved complete renal response. This difference was not statistically significant.

This finding is important, because while low-dose cyclophosphamide – the "Euro-Lupus regimen" – has been shown to be as effective as standard and more toxic higher dosing, studies had primarily included a European Caucasian population. It was unclear whether the low-dose regimen would be as effective in a multiracial and multiethnic population, said Dr. Rovin of Ohio State University Medical Center.

No differences were seen between the treatment and control groups with respect to anti-dsDNA or complement levels and/or the frequency of serious or infectious adverse events or study withdrawals.

Of note, azathioprine was stopped in treatment group patients who achieved complete renal response – but not control group patients who achieved complete renal response. These patients were followed to 52 weeks. At that time, 50% and 62% of the treatment group and control group patients, respectively, who were complete responders at 24 weeks still met the criteria for complete response, Dr. Rovin said.

While abatacept did not increase complete response rates, the treatment was associated with maintenance of complete renal response to 1 year despite discontinuation of maintenance immunosuppression in the treated patients and continued azathioprine treatment in the control group. This suggests that abatacept may reduce the need for maintenance immunosuppression, he said.

While it was disappointing that the addition of abatacept to background induction therapy with low-dose IV cyclophosphamide and corticosteroids did not improve the complete renal response rate in this study – despite murine models suggesting that the use of abatacept and IV cyclophosphamide act synergistically to arrest lupus nephritis progression – the findings offer two very important lessons for clinical practice, he said.

"We can take the low-dose cyclophosphamide regimen and potentially use that with good results in our [multiethnic, multiracial] patient population that we see here in this country, and I think that’s a huge step forward. It gives us another option to use besides mycophenolate mofetil and high-dose cyclophosphamide," he said, adding that the low-dose IV cyclophosphamide regimen is well tolerated and delivers a total dose of only 3 g of the drug – a dose that generally does not predispose to premature ovarian failure.

This is particularly important, because women of childbearing years comprise a majority of the patient population with lupus nephritis, he explained.

"We know from the Euro-Lupus trial that the low-dose regimen, over 10 years, provided the same maintenance of renal function as the high-dose regimen, so we have very good long-term follow-up. We don’t quite have that yet with mycophenolate mofetil, so I think that for those of us who are very frequent users of cyclophosphamide, this is a very good alternative to the high-dose, highly toxic regimen that has for so long been the standard of care," he said.

This study was funded by the National Institute of Allergy and Infectious Diseases via the Immune Tolerance Network. Bristol Myers Squibb provided the study drug. Dr. Rovin reported ties to Genentech, Questcor, TEVA, Biogen-IDEC, HGS, Johnson & Johnson, Roche, BMS, and TG Therapeutics.

ATLANTA – Adding abatacept to low-dose intravenous cyclophosphamide did not improve the rate of complete renal response at 1 year, compared with IV cyclophosphamide alone, in patients with class III or IV lupus nephritis in the randomized, controlled ACCESS Trial.

The phase II findings suggested, however, that abatacept reduced the need for maintenance immunosuppression, and they also demonstrated for the first time that low-dose IV cyclophosphamide may have applicability in racially and ethnically diverse patients with lupus nephritis, Dr. Brad H. Rovin reported at Kidney Week 2013.

The overall complete renal response rates were similar at 33% and 31%, respectively, in 134 patients with class III or IV lupus nephritis who were enrolled in the trial, treated with a steroid taper and 500 mg of IV cyclophosphamide every 2 weeks for 6 weeks followed by 2 mg/kg of azathioprine daily. Patients then were randomized to receive abatacept or placebo at week 0, 2, and 4 and then monthly.

Complete plus partial responses occurred in 59% of patients in each arm, Dr. Rovin said at the conference, which was sponsored by the American Society of Nephrology.

Patients in the study had a urine protein-to-creatinine ratio (UPCR) greater than 1. Complete renal response was defined as a UPCR of less than 0.5, serum creatinine at normal or within 25% of baseline, and prednisone dose tapered to 10 mg daily or less. African Americans comprised 39% of the cohort, and Hispanic/Mestizo patients comprised 40%.

Among the African American patients, 33% in the treatment group, compared with 16% in the placebo group, achieved complete renal response. This difference was not statistically significant.

This finding is important, because while low-dose cyclophosphamide – the "Euro-Lupus regimen" – has been shown to be as effective as standard and more toxic higher dosing, studies had primarily included a European Caucasian population. It was unclear whether the low-dose regimen would be as effective in a multiracial and multiethnic population, said Dr. Rovin of Ohio State University Medical Center.

No differences were seen between the treatment and control groups with respect to anti-dsDNA or complement levels and/or the frequency of serious or infectious adverse events or study withdrawals.

Of note, azathioprine was stopped in treatment group patients who achieved complete renal response – but not control group patients who achieved complete renal response. These patients were followed to 52 weeks. At that time, 50% and 62% of the treatment group and control group patients, respectively, who were complete responders at 24 weeks still met the criteria for complete response, Dr. Rovin said.

While abatacept did not increase complete response rates, the treatment was associated with maintenance of complete renal response to 1 year despite discontinuation of maintenance immunosuppression in the treated patients and continued azathioprine treatment in the control group. This suggests that abatacept may reduce the need for maintenance immunosuppression, he said.

While it was disappointing that the addition of abatacept to background induction therapy with low-dose IV cyclophosphamide and corticosteroids did not improve the complete renal response rate in this study – despite murine models suggesting that the use of abatacept and IV cyclophosphamide act synergistically to arrest lupus nephritis progression – the findings offer two very important lessons for clinical practice, he said.

"We can take the low-dose cyclophosphamide regimen and potentially use that with good results in our [multiethnic, multiracial] patient population that we see here in this country, and I think that’s a huge step forward. It gives us another option to use besides mycophenolate mofetil and high-dose cyclophosphamide," he said, adding that the low-dose IV cyclophosphamide regimen is well tolerated and delivers a total dose of only 3 g of the drug – a dose that generally does not predispose to premature ovarian failure.

This is particularly important, because women of childbearing years comprise a majority of the patient population with lupus nephritis, he explained.

"We know from the Euro-Lupus trial that the low-dose regimen, over 10 years, provided the same maintenance of renal function as the high-dose regimen, so we have very good long-term follow-up. We don’t quite have that yet with mycophenolate mofetil, so I think that for those of us who are very frequent users of cyclophosphamide, this is a very good alternative to the high-dose, highly toxic regimen that has for so long been the standard of care," he said.

This study was funded by the National Institute of Allergy and Infectious Diseases via the Immune Tolerance Network. Bristol Myers Squibb provided the study drug. Dr. Rovin reported ties to Genentech, Questcor, TEVA, Biogen-IDEC, HGS, Johnson & Johnson, Roche, BMS, and TG Therapeutics.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The global prevalence of maintenance dialysis for end-stage renal disease has increased 165% over the past 2 decades – a rate that has far outpaced that of population growth in most regions of the world, according to Dr. Bernadette A. Thomas.

The findings – the first to quantify the global burden of end-stage renal disease – underscore a need for improved detection of early chronic kidney disease and for treatment aimed at preventing end-stage renal disease (ESRD), because a continued rise in the prevalence of maintenance dialysis may not be sustainable, Dr. Thomas of the University of Washington, Seattle, said at Kidney Week 2013.

From 1990 to 2010, the global prevalence of maintenance dialysis in areas with universal dialysis access increased 134%, after adjustment for population growth and aging. The increase was 145% among women and 123% among men. Even in countries with a lack of universal access, the adjusted prevalence increased by 102% (116% for women and 90% for men).

The regions that did not experience an increase in dialysis prevalence included Oceania, South Asia, Central Sub-Saharan Africa, Eastern Europe, and tropical Latin America, Dr. Thomas said at the conference, which was sponsored by the American Society of Nephrology.

The findings are based on data extracted from the Global Burden of Disease database, the largest existing database for global causes of morbidity and mortality. Prevalence estimates were based on national and regional ESRD registries and a structured literature review. Data from 23 countries with universal dialysis access and from 138 countries with partial access were included; data from 26 countries that lack routine access were excluded.

"The statistics are appalling," American Society of Nephrology President Bruce A. Molitoris of Indiana University, Indianapolis, noted during a press briefing. Dr. Molitoris called for stepped-up efforts to educate the public about the importance of kidney health.

"We have targeted the patients in the past [via] patient education, and we have not presented, I think, a fair outlook to the public of the potential importance of kidney disease," he said.

Up to one-third of U.S. residents will, at some point in their lives, have severe kidney disease, Dr. Molitoris said, and 8% of African Americans and 3.6% of the total population will go on dialysis or need a transplant.

"And yet, people think they are immune to kidney disease," he cautioned. "The field is in need of innovation; the field is in need of individualization of care. And to do that, we have to have public awareness."

Kidney disease ranks near the bottom when it comes to research funding, and public awareness will go a long way toward changing that, he added.

Dr. Molitoris said he is optimistic that as the pharmaceutical industry continues taking an interest in kidney disease, and as public awareness increases, funding – and therefore innovation – will also increase. He said he envisions a time when the public will be as aware of their kidney function level as they are of their cholesterol level.

"With what is going on in science and technology and biology, it’s not a far leap for us to make major strides," he said.

The study by Dr. Thomas was supported by a private foundation. Dr. Thomas reported having no relevant financial disclosures. Dr. Molitoris reported consultancy, ownership interest, research funding, honoraria, and/or a scientific advisory or membership role for numerous companies. He also reported a patent/invention with FAST Diagnostics, Indiana University.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.

ATLANTA – The combined use of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with an increased risk of hyperkalemia and acute kidney injury in patients with diabetic nephropathy in a randomized, controlled trial that was halted early because of these safety concerns.

"The risk-benefit ratio does not support the use of these medications – they’re not safe," noted Dr. Linda F. Fried, speaking at Kidney Week 2013.

The VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes) study involved 1,448 patients with type 2 diabetes and moderate diabetic nephropathy who were treated for at least 30 days with 100 mg daily of the angiotensin-receptor blocker (ARB) losartan, as is standard practice in patients with diabetes. The patients were randomized to also receive 10-40 mg daily of the angiotensin-converting enzyme (ACE) inhibitor lisinopril or placebo.

At a median follow-up of 2.2 years as of the time the study was stopped, 152 patients in the combination-therapy group and 132 in the placebo group (21% vs. 18.2%) experienced the composite primary endpoint of first occurrence of a predefined change in the estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or death (hazard ratio with combination therapy, 0.88). The difference between the groups was not statistically significant, said Dr. Fried, professor of medicine, epidemiology, and clinical and translational science at the University of Pittsburgh and chief of peritoneal dialysis at Veterans Affairs Pittsburgh Healthcare System.

Despite an early trend toward benefit, this trend diminished over time so that no significant difference was seen between the groups in the secondary renal end point of a first occurrence of a decline in the eGFR or ESRD (hazard ratio, 0.78). Also, no difference was seen between the groups with respect to the safety outcome of mortality (HR for death, 1.04). The rate of cardiovascular events in the groups was also similar.

However, there was a greater than twofold increase in the risk of hyperkalemia in the combination therapy group, compared with the placebo group (6.3 vs. 2.6 events/100 person-years), and a nearly twofold increase in the risk of acute kidney injury in the combination therapy group (12.2 vs. 6.7 event/100 person-years), Dr. Fried said at the conference, which was sponsored by the American Society of Nephrology.

The findings were published concurrently in the New England Journal of Medicine (2013 Nov. 9 [doi10.1056/NEJMoa1303154]).

Patients in the study had type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300, and an eGFR of 30.0 to 89.9 mL/minute per 1.73 m² or body-surface area. Change in eGFR as specified for the composite primary endpoint of the study was a decline of at least 30 mL/minute per 1.73 m² in those with an initial eGFR of at least 60 mL/minute per 1.73 m², or a decline of at least 50% if the initial eGFR was less than 60 mL/minute per 1.73 m².

Treatment with medications that block angiotensin are known to slow loss of kidney function in individuals with diabetes and proteinuria. This is true for both ACE inhibitors and ARBs, which have different mechanisms of action, but the percentage of patients who progress to dialysis despite treatment with one of these medications remains high, Dr. Fried said.

"So we need more treatments. A question that comes up is, ‘Would more intensive blockade of angiotensin – using two (drugs) together – slow decline?’ ... The thought was that treatments that lowered proteinuria should lower progression. We did see the lower proteinuria but without the benefit on the endpoints," she said during a press briefing in advance of the presentation of the late-breaking abstract.

Instead, it became clear that the treatment was associated with significantly more hyperkalemia and kidney injury, she said, noting that significantly more patients in the combination therapy group experienced acute kidney injury requiring hospitalization, indicating the problem was not just one of "lab abnormalities."

In fact, for every 100 persons followed for 1 year, there were 17 more admissions to the hospital, Dr. Fried said, noting that "these were not small differences in safety outcomes."

"The risk-benefit ratio does not support the use of these medications – they’re not safe." she concluded.

The VA-Nephron-D study was supported by the cooperative studies program of the Department of Veterans Affairs Office of Research and Development. The Investigator-Initiated Studies Program of Merck provided the study drugs. Dr. Fried reported receiving support from Reata Pharmaceuticals as a site investigator for a study. Other studies authors reported receiving lecture or consulting fees from Merck, Sanofi-Aventis, Complex, and/or CytoPherx.