Nephrology

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – Once-daily add-on liraglutide reduces HbA_1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.

The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.

In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA_1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.

No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.

Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.

Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.

Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.

Subjects were adults with body mass index of 20-45 kg/m² and HbA_1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m²; modification of diet in renal disease).

“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.

Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.

Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.

The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.

The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

[email protected]

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

[email protected]

PHILADELPHIA – Extended time on hemodialysis each week produced some modest improvement in lab values but didn’t result in any overall increases in quality of life for patients.

A dialysis regimen of at least 24 hours weekly failed to confer any significant benefits on blood pressure, weight, or 12-month cardiovascular outcomes, Dr. Meg Jardine said at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

A follow-up period of 12 months, however, probably isn’t long enough to detect any potential cardiovascular benefits, noted Dr. Jardine of the George Institute of Global Health of Sydney.

The ACTIVE Dialysis Multinational Trial was conducted at 40 centers in Australia, China, New Zealand, and the U.K. It randomized 200 patients with end-stage renal disease to either standard dialysis (12-18 hours weekly) or the extended regimen (24-28 hours). Dialysis could be carried out at home or in a center. The primary endpoint was any change in health-related quality of life as measured on the EQ-5D, an internationally validated health quality of life measure, which was administered every 3 months. The EQ-5D score ranges from 0-1, with 0 being death and 1 being perfect health.

Secondary outcomes included overall survival, changes in biochemical and hematological markers, and safety including vascular access issues. A prespecified subanalysis examined changes in left ventricular mass index.

Patients were a mean of 52 years old. Most (70%) were male. At baseline, they received dialysis for a mean of 14 hours per week; 88% of dialysis was performed at a dialysis center. Access was via a native arteriovenous fistula in 84% of patients. The baseline EQ-5D score was 0.76 in the standard-dialysis group and 0.79 in the extended-dialysis group.

After 12 months, neither of the groups experienced any significant improvements in overall quality of life measures, Dr. Jardine said. There was a nonsignificant indication that the physical health subscale improved among patients who had the extended dialysis. There was no change in the mental health subscale in either group.

Patients in the extended-dialysis group did experience some significant improvements in laboratory measures. Potassium and phosphate levels declined significantly from baseline – enough to eliminate the need for a phosphate binder for many, she said. Calcium increased significantly, as did hemoglobin.

Both diastolic and systolic blood pressure improved somewhat, and although those improvements were not statistically significant, they did confer a significant decrease in the need for antihypertensive therapy.

At the 12-month follow up, imaging revealed that patients in the extended-dialysis group had a greater left ventricular mass – a mean of 2.84 g/m² more than that seen in the standard-dialysis group. The short follow-up time, however, makes interpretation of this finding difficult, Dr. Jardine said.

There were no significant differences in serious adverse effects between the groups. There were two deaths and three transplants in the standard arm, compared with five deaths and two transplants in the extended dialysis arm – not a significant difference.

Dr. Jardine disclosed that she has received honoraria from Servier Laboratories and Amgen.

[email protected]

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.

PHILADELPHIA – ZS-9, an investigational cation exchanger designed to trap potassium in the gut, effectively and rapidly restores and maintains normokalemia in hyperkalemic patients with diabetes and significant renal impairment, according to a subgroup analysis of data from a randomized, placebo-controlled phase III trial.

Treatment with the first-in-class insoluble, nonabsorbed zirconium silicate, which was designed and engineered to have a three-dimensional crystalline lattice structure that preferentially traps potassium ions, was shown to have clinically and statistically significant benefit at daily oral doses of 5 mg and 10 mg, compared with placebo in the overall study population of 753 patients with hyperkalemia and underlying diabetes, heart failure, or chronic kidney disease.

The current analysis included 366 patients who had diabetes and an estimated glomerular filtration rate less than 60 mL/min/1.73m². The patients, who had baseline potassium levels of 5.0-6.5 mEq/L (mean of 5.3 mEq/L) were randomized to oral ZS-9 at doses of 1.25, 2.5, 5, or 10 g or placebo given three times daily for the first 48 hours. Following this acute phase, those with a potassium level of 3.5-5.0 mEq/L were rerandomized to either the same ZS-9 acute-phase dose once daily for days 3-15 or placebo.

In the subgroup, ZS-9 treatment was associated with a significant decrease in potassium at 48 hours (decreases of -0.45, -0.59, and -0.81 mEq/L in the 2.5-, 5-, and 10-g groups, respectively, compared with +0.24 mEq/L in the placebo group, Dr. Bhupinder Singh reported at the meeting sponsored by the American Society of Nephrology.

During the maintenance phase, patients receiving a 10-g dose of ZS-9 maintained normokalemia (4.5 mEq/L at day 3 vs. 4.6 mEq/L at day 15) vs. placebo (4.4 mEq/L at day 3, vs. 5.1 mEq/L at day 15). Similar results were seen in the 5-mg treatment group, Dr. Singh of Apex Research, Riverside, Calif. said.

“Hyperkalemia is a common and serious complication in patients with diabetes who have chronic kidney disease, particularly those who are treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Even mild to moderate hyperkalemia has been recently shown to be associated with increased mortality,” Dr. Singh said, noting that concerns about the seriousness of hyperkalemia have likely led to under-prescription of RAAS inhibitors, which have been proven to have cardio- and renoprotective action, but which are associated with hyperkalemia.

In head-to-head in vitro studies, ZS-9 has been shown to be more than 125 times more selective than sodium polystyrene sulfonate (SPS) – the current mainstay of treatment for hyperkalemia), and to have more than 9 times the potassium-binding capacity.

In the current analysis, ZS-9 was associated with a “fairly acute” effect, reducing potassium levels significantly within 1 hour, and to less than 5 mEq/L within 4 hours. The study also was published Nov. 21 in the New England Journal of Medicine (doi:10.1056/NEJMoa1411487).

In both the overall study population and the subgroup with diabetes and chronic kidney disease, ZS-9 discontinuation at the end of the study was associated with recurrence of hyperkalemia, indicating a need for continued use. The adverse event profile was similar in the treatment and placebo groups in both studies.

The findings suggest that long-term treatment with ZS-9 may allow continuation of chronic RAAS inhibition in patients with diabetes and chronic kidney disease, Dr. Sing said, adding that long-term treatment studies are underway.

This study was funded by ZS Pharma Inc., which is developing ZS-9. Dr. Singh is a consultant to ZS Pharma Inc.

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

[email protected]

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

[email protected]

PHILADELPHIA – An experimental dialysis device safely and dramatically reduced the viral load in a critically ill Ebola patient treated in Frankfurt, Germany.

Dialysis performed using the device resulted in a reduction in viral load from 400,000 copies/mL to 1,000 copies/mL in the 36-year-old patient, said Dr. Helmut Geiger, chief of nephrology at Frankfurt University Hospital, at Kidney Week 2014.

The patient, a pediatrician who had treated Ebola patients in Sierra Leone, was diagnosed in September. He was transferred in October to Frankfurt University Hospital, where he presented with fever, chills, and weakness, and rapidly deteriorated. He developed multiorgan failure – including kidney failure – despite treatment with various experimental therapies.

The patient was placed on dialysis. The experimental device – the Hemopurifier, made by Aethlon Medical of San Diego – was incorporated into the treatment, with special approval from Germany’s Federal Institute for Drugs and Medical Devices, Dr. Geiger said at the meeting, which was sponsored by the American Society of Nephrology.

The Hemopurifier is a first-in-class biofiltration device designed to eliminate viruses and immunosuppressive proteins from the circulatory system of infected individuals, according to Aethlon. The company has been testing the device in patients with hepatitis C and in HIV patients in India. Aethlon plans to initiate U.S. clinical studies under an investigational device exemption approved by the U.S. Food and Drug Administration.

Successful in vitro validation studies have been conducted by researchers at the U.S. Army Medical Research Institute of Infectious Diseases and the Centers for Disease Control and Prevention.

The Hemopurifier is a cylindrical cartridge that attaches to an existing dialysis machine. Inside, a gluelike protein selectively binds to viral particles and fragments, removing them from blood circulation.

The patient treated in Frankfurt by Dr. Geiger and his team underwent a 6.5-hour dialysis procedure using the device, and an analysis performed at a laboratory equipped to handle Ebola virus showed that the device had trapped 242 million copies of the virus, Dr. Geiger said.

The patient is now out of isolation, off dialysis, and in very good condition, he said, noting that the patient would be discharged within days.

Although additional study is needed, it appears that the Hemopurifier device may have contributed to the patient’s recovery, Dr. Geiger said, and no adverse events occurred during the treatment. The device ultimately could play a role in treating multiple types of viral infection, he added.

Use of the Hemopurifier is safe and feasible, the device can be used with intermittent hemodialysis or in the setting of continuous renal replacement therapy, and it represents a promising new supportive tool for severe Ebola infection, he concluded.

Dr. Geiger reported having consultancy agreements with AbbVie, Amgen, and Otsuka, and receiving research funding from Fresenius Medical Care.

[email protected]

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

[email protected]

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

[email protected]

PHILADELPHIA- Neither perioperative aspirin nor clonidine reduced the risk of an acute kidney injury in patients who underwent major noncardiac surgery, a large randomized trial has determined.

The risk of an acute kidney injury (AKI) associated with aspirin was 10% more than placebo, and the risk with clonidine, 3% more, but those differences were not statistically significant, Dr. Amit X. Garg and associates wrote online in JAMA (JAMA 2015; doi:10.1001/jama.2014.15284).

Both drugs increased the risk of postoperative conditions that are associated with AKI, Dr. Garg of the London Health Sciences Centre and Western University, London, Ontario, and his co-authors noted. The study was simultaneously presented at Kidney Week 2014, which was sponsored by the American Society of Nephrology.

In fact, there was some suggestion that the drugs increased the risk of severe AKI, he said at the meeting. “But these were secondary measures and need to be interpreted cautiosuly, because the absolute number of severe AKIs was quite small.”

The AKI investigation was a substudy of the Perioperative Ischemia Evaluation-2, (POISE-2) trial, which evaluated the risk of 30-day mortality or nonfatal myocardial infarction among 6,905 surgical patients with a moderate to high risk of a perioperative cardiac event. The aspirin regimen called for 200 mg before surgery and then 100 mg daily for up to 30 days after surgery. The clonidine regimen was 0.2 mg orally 2-4 hours before surgery, followed by a 0.3 mg/day transdermal patch worn for 72 hours after surgery. Both groups also had a placebo arm.

The patients were a mean of 69 years old. Cardiovascular disease was present in about 30%; these included coronary artery disease, stroke, and peripheral vascular disease. About a quarter smoked; 36% had diabetes; 86% had hypertension; 2% had atrial fibrillation. Medications included COX-2 inhibitors; statins; ACE, ARB or direct renin inhibitors; and antihypertensives.

At baseline about 24% had an estimated glomerular filtration rate of 60 ml/min or lower per 1.73 m².

Surgical procedures were urgent or emergent, major vascular, major thoracic, major urological or gynecologic, and other unspecified procedures.

Aspirin did not reduce the risk of an AKI compared to placebo. AKI occurred in 462 patients taking aspirin and 426 taking placebo (13.4% vs. 12.3% respectively; adjusted risk ratio 1.10). Nor did clonidine reduce the risk of AKI compared to placebo. AKI occurred in 449 taking aspirin and 439 taking placebo (13% and 12.7% respectively; adjusted risk ratio 1.03). Neither of these findings was statistically significant.

AKI-related dialysis within 30 days occurred in 0.6% those taking aspirin and 0.3% of the matched placebo patients - a nonsignificant difference. Serum creatinine increased a mean of 11% with aspirin vs. 11% with placebo.

Dialysis was necessary in 0.5% of those taking clonidine and 0.3% of the matched placebo patients - another nonsignificant finding. A history of preoperative chronic kidney disease did not alter either of these findings.

A post hoc analysis determined that both drugs increased the incidence of conditions known to boost the risk of kidney injury. Aspirin increased the risk of major bleeding, which was associated with a greater risk of AKI (23.3% when bleeding occurred vs 12.3% when it did not; adjusted risk ratio 2.20).

Because of this doubling of risk, Dr. Garg suggested moderating pre-operative aspirin exposure in these patients.

“Among patients taking aspirin as part of a long-term regimen, these results support holding it for at least 3 days before surgery and then restarting it a week after surgery,” he recommended.

Clonidine increased the risk of clinically important hypotension, which was also related in turn to AKI (14.3% when hypotension was present vs. 11.8% when it was not; adjusted risk ratio for AKI 1.34).

Dr. Garg had no financial disclosures. A number of the POISE-2 investigators reported financial relationships with pharmaceutical companies.

[email protected]

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

PHILADELPHIA – Dual blockade of the renin-angiotensin-aldosterone system with combined angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy was no more effective for maintaining blood pressure control than was ACE inihibitor monotherapy in patients with moderately advanced autosomal dominant polycystic kidney disease and stage 3 chronic kidney disease.

That finding emerged from a study of the randomized placebo-controlled Halt Progression of Polycystic Kidney Disease (HALD-PKD) trial reported at Kidney Week 2014.

The composite primary outcome of time to death, end-stage renal disease, or 50% reduction from baseline in estimated glomerular filtration rate (eGFR) was similar in 242 patients with stages 1-3 autosomal dominant polcystic kidney disease (ADPKD) randomized to receive lisinopril plus placebo, and in 243 such patients randomized to receive lisinopril plus telmisartan (number of events in the groups, respectively, 116 and 115; hazard ratio, 1.08), said Dr. Vicente E. Torres.

Also, no significant differences were seen between the groups with respect to the individual components of the composite outcome; the hazard ratios for death, end-stage renal disease, and 50% reduction in eGFR were 0.93, 0.78, and 1.05, respectively, Dr. Torres of the Mayo Clinic College of Medicine, Rochester, Minn. said at the meeting, which was sponsored by the American Society of Nephrology.

The findings were simultaneously published online Nov. 15 in the New England Journal of Medicine (N Engl J Med 2014 Nov. 15[doi: 10.1056/NEJMoa1402686]).

The rates of change in eGFR urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, also were similar in the two groups, Dr. Torres said.

Participants in the double-blind study were enrolled from February 2006 through June 2009. They were aged 18 to 64 years and had eGFR of 25 to 60 ml per minute per 1.73 m² of body-surface area. Lisinopril doses in both groups were adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg, and patients were followed for a mean of 5 years. Systolic blood pressures and mean arterial pressures remained within the target range throughout the trial in 73% to 86% and in 70% to 83% of participants, respectively. Diastolic pressures were in the target range in 56% to 65% of participants.

Hypertension develops early and contributes to the progression of disease in patients with ADPKD, and the renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in ADPKD patients. Angiotensin-converting enzyme inhibitors like lisinopril are known to slow the progression of renal dysfunction in non-diabetic kidney disease, and thus have become standard first-line agents for the treatment of hypertension in patients with ADPKD, Dr. Torres said.

“Although ACE inhibitors have become the first-line therapy for hypertension in patients with chronic kidney disease, including ADPKD, their renoprotective effect may be limited by compensatory-feedback increases in renin release and the generation of angiotensin,” he and his colleagues wrote, noting that dual RAAS blockade has been proposed as a strategy to circumvent this compensatory feedback.

The current study showed that adding telmisartan did result in slightly lower blood pressures, but did not reduce the incidence of primary or secondary outcomes.

Both combination therapy and lisinopril monotherapy were safe, with a similar rate of adverse events in the two groups, but the addition of an ARB did not confer additional benefit, Dr. Torres said, concluding that ACE inhibitor monotherapy achieved excellent standard blood pressure control in more than 70% of patients with stages 1-3 ADPKD.The HALT-PKD trial was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (including a grant to Dr. Torres), the National Center for Research Resources’ General Clinical Research Centers, the National Center for Advancing Translational Sciences’ Clinical and Translational Science Awards, the Zell Family Foundation, and the PKD Foundation.

A multitarget therapy of mycophenolate mofetil and tacrolimus for lupus nephritis induction therapy led to almost twice as many complete remissions as did intravenous cyclophosphamide in an open-label, randomized, controlled trial.

“Because immune dysregulation is fundamental to pathogenesis of lupus nephritis, with both B and T cells involved in the development of the disease, it may be necessary to target multiple aspects of the immune response using combined immunosuppressants,” wrote Dr. Zhi-Hong Liu of Nanjing (China) University and her colleagues (Ann. Intern. Med. 2014 Nov. 11 [doi:10.7326/M14-1030]).

Between April 2009 and June 2011, 368 adults aged 18-65 years from 26 renal centers in China were randomized to receive mycophenolate mofetil (MMF) and tacrolimus with a steroid or IV cyclophosphamide with a steroid for 24 weeks. A total of 362 received medication (6 did not receive their assigned cyclophosphamide treatment for unknown reasons), and 310 completed the whole 24-week course of treatment. All participants in the study had biopsy-proven lupus nephritis diagnosed within the previous 6 months and had not been previously treated with MMF, cyclophosphamide, tacrolimus, or high-dose methylprednisolone, nor had they had renal replacement therapy, plasmapheresis, or IV gamma globulin therapy in the previous 12 weeks.

All patients began by receiving IV methylprednisolone pulse therapy (0.5 g/day) for 3 days and then oral prednisone (0.6 mg/kg) daily for 4 weeks, with prednisone tapering to 10 mg/day for the remainder of the study period. Following methylprednisolone pulse therapy, the multitarget group received MMF (0.5 g twice daily) and tacrolimus (2 mg twice daily) while the comparison group received IV cyclophosphamide (initially 0.75 g/m² body surface area, then adjusted to 0.5-1.0 g/m²).

Nearly half – 45.9% – of patients in the multitarget group achieved full remission, whereas 25.6% of patients receiving IV cyclophosphamide showed complete remission (P < .001). The investigators defined complete remission as a 24-hour urinary protein excretion of 0.4 g or less, the absence of active urine sediments, a serum albumin level of 35 g/L or greater, and normal serum creatinine.

Results on secondary endpoints also favored multitarget therapy. The percentage of patients who had an overall response to treatment (complete and partial remissions) was 83.5% for multitarget therapy and 63% for cyclophosphamide (P < .001). Multitarget therapy patients responded to treatment at a median of 8.9 weeks, compared with cyclophosphamide-treated patients at 13 weeks. The investigators defined partial response as a 50% or greater reduction in proteinuria and urine protein less than 3.5 g/24 hours, a serum albumin level of 30 g/L or higher, and a normal or 25% or lower increase in serum creatinine level from baseline.

After treatment, patients in the multitarget therapy group also had significantly better results on other secondary endpoints, including changes in urine protein, serum albumin, systemic lupus erythematosus disease activity score, and C3 levels.

Adverse events occurred among 50.3% of multitarget recipients and 52.5% of cyclophosphamide recipients. More patients who received multitarget therapy had a serious adverse event (7.2% vs. 2.8%, respectively), and more patients withdrew from the multitarget therapy group (5.5% vs. 1.7%), but there were no statistically significant differences between the groups for either comparison.

The study was supported by the National Basic Research Program of China and the National Key Technology R&D Programs. Information on disclosures was unavailable at the time of publication.

A multitarget therapy of mycophenolate mofetil and tacrolimus for lupus nephritis induction therapy led to almost twice as many complete remissions as did intravenous cyclophosphamide in an open-label, randomized, controlled trial.

“Because immune dysregulation is fundamental to pathogenesis of lupus nephritis, with both B and T cells involved in the development of the disease, it may be necessary to target multiple aspects of the immune response using combined immunosuppressants,” wrote Dr. Zhi-Hong Liu of Nanjing (China) University and her colleagues (Ann. Intern. Med. 2014 Nov. 11 [doi:10.7326/M14-1030]).

Between April 2009 and June 2011, 368 adults aged 18-65 years from 26 renal centers in China were randomized to receive mycophenolate mofetil (MMF) and tacrolimus with a steroid or IV cyclophosphamide with a steroid for 24 weeks. A total of 362 received medication (6 did not receive their assigned cyclophosphamide treatment for unknown reasons), and 310 completed the whole 24-week course of treatment. All participants in the study had biopsy-proven lupus nephritis diagnosed within the previous 6 months and had not been previously treated with MMF, cyclophosphamide, tacrolimus, or high-dose methylprednisolone, nor had they had renal replacement therapy, plasmapheresis, or IV gamma globulin therapy in the previous 12 weeks.

All patients began by receiving IV methylprednisolone pulse therapy (0.5 g/day) for 3 days and then oral prednisone (0.6 mg/kg) daily for 4 weeks, with prednisone tapering to 10 mg/day for the remainder of the study period. Following methylprednisolone pulse therapy, the multitarget group received MMF (0.5 g twice daily) and tacrolimus (2 mg twice daily) while the comparison group received IV cyclophosphamide (initially 0.75 g/m² body surface area, then adjusted to 0.5-1.0 g/m²).

Nearly half – 45.9% – of patients in the multitarget group achieved full remission, whereas 25.6% of patients receiving IV cyclophosphamide showed complete remission (P < .001). The investigators defined complete remission as a 24-hour urinary protein excretion of 0.4 g or less, the absence of active urine sediments, a serum albumin level of 35 g/L or greater, and normal serum creatinine.

Results on secondary endpoints also favored multitarget therapy. The percentage of patients who had an overall response to treatment (complete and partial remissions) was 83.5% for multitarget therapy and 63% for cyclophosphamide (P < .001). Multitarget therapy patients responded to treatment at a median of 8.9 weeks, compared with cyclophosphamide-treated patients at 13 weeks. The investigators defined partial response as a 50% or greater reduction in proteinuria and urine protein less than 3.5 g/24 hours, a serum albumin level of 30 g/L or higher, and a normal or 25% or lower increase in serum creatinine level from baseline.

After treatment, patients in the multitarget therapy group also had significantly better results on other secondary endpoints, including changes in urine protein, serum albumin, systemic lupus erythematosus disease activity score, and C3 levels.

Adverse events occurred among 50.3% of multitarget recipients and 52.5% of cyclophosphamide recipients. More patients who received multitarget therapy had a serious adverse event (7.2% vs. 2.8%, respectively), and more patients withdrew from the multitarget therapy group (5.5% vs. 1.7%), but there were no statistically significant differences between the groups for either comparison.

The study was supported by the National Basic Research Program of China and the National Key Technology R&D Programs. Information on disclosures was unavailable at the time of publication.

A multitarget therapy of mycophenolate mofetil and tacrolimus for lupus nephritis induction therapy led to almost twice as many complete remissions as did intravenous cyclophosphamide in an open-label, randomized, controlled trial.

“Because immune dysregulation is fundamental to pathogenesis of lupus nephritis, with both B and T cells involved in the development of the disease, it may be necessary to target multiple aspects of the immune response using combined immunosuppressants,” wrote Dr. Zhi-Hong Liu of Nanjing (China) University and her colleagues (Ann. Intern. Med. 2014 Nov. 11 [doi:10.7326/M14-1030]).

Between April 2009 and June 2011, 368 adults aged 18-65 years from 26 renal centers in China were randomized to receive mycophenolate mofetil (MMF) and tacrolimus with a steroid or IV cyclophosphamide with a steroid for 24 weeks. A total of 362 received medication (6 did not receive their assigned cyclophosphamide treatment for unknown reasons), and 310 completed the whole 24-week course of treatment. All participants in the study had biopsy-proven lupus nephritis diagnosed within the previous 6 months and had not been previously treated with MMF, cyclophosphamide, tacrolimus, or high-dose methylprednisolone, nor had they had renal replacement therapy, plasmapheresis, or IV gamma globulin therapy in the previous 12 weeks.

All patients began by receiving IV methylprednisolone pulse therapy (0.5 g/day) for 3 days and then oral prednisone (0.6 mg/kg) daily for 4 weeks, with prednisone tapering to 10 mg/day for the remainder of the study period. Following methylprednisolone pulse therapy, the multitarget group received MMF (0.5 g twice daily) and tacrolimus (2 mg twice daily) while the comparison group received IV cyclophosphamide (initially 0.75 g/m² body surface area, then adjusted to 0.5-1.0 g/m²).

Nearly half – 45.9% – of patients in the multitarget group achieved full remission, whereas 25.6% of patients receiving IV cyclophosphamide showed complete remission (P < .001). The investigators defined complete remission as a 24-hour urinary protein excretion of 0.4 g or less, the absence of active urine sediments, a serum albumin level of 35 g/L or greater, and normal serum creatinine.

Results on secondary endpoints also favored multitarget therapy. The percentage of patients who had an overall response to treatment (complete and partial remissions) was 83.5% for multitarget therapy and 63% for cyclophosphamide (P < .001). Multitarget therapy patients responded to treatment at a median of 8.9 weeks, compared with cyclophosphamide-treated patients at 13 weeks. The investigators defined partial response as a 50% or greater reduction in proteinuria and urine protein less than 3.5 g/24 hours, a serum albumin level of 30 g/L or higher, and a normal or 25% or lower increase in serum creatinine level from baseline.

After treatment, patients in the multitarget therapy group also had significantly better results on other secondary endpoints, including changes in urine protein, serum albumin, systemic lupus erythematosus disease activity score, and C3 levels.

Adverse events occurred among 50.3% of multitarget recipients and 52.5% of cyclophosphamide recipients. More patients who received multitarget therapy had a serious adverse event (7.2% vs. 2.8%, respectively), and more patients withdrew from the multitarget therapy group (5.5% vs. 1.7%), but there were no statistically significant differences between the groups for either comparison.

The study was supported by the National Basic Research Program of China and the National Key Technology R&D Programs. Information on disclosures was unavailable at the time of publication.