Nephrology

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

BOSTON - Among 839 patients with systemic lupus erythematosus (SLE) and no evidence of lupus nephritis at the time of diagnosis, the presence of discoid lupus erythematosus (DLE) at SLE onset was associated with a 64% reduction in risk for developing lupus nephritis.

“Our data suggest that while SLE patients who have DLE preceding the diagnosis of SLE are at low risk of further lupus nephritis, SLE patients without discoid lupus at onset should be monitored for early diagnosis of lupus nephritis and adequate treatment,” said Dr. Guillermo Javier Pons-Estel from the department of autoimmune disease, L’Institut Clínic de Medicina i Dermatologia, Hospital Clinic, in Barcelona, Spain.

He reported results of a study comparing lupus nephritis rates in patients enrolled in the GLADEL (Grupo di Latino Americano De Estudio de Lupus) longitudinal study of Latin American patients with SLE.

DLE is characterized by the appearance of scarring inflammatory plaques that heal but leave central scars, atrophy, and dyspigmentation. It occurs at onset in approximately 5%-11% of all patients with SLE, and after a delay of 3-5 years from onset in a small proportion of patients, he said at the annual meeting of the American College of Rheumatology.

There is conflicting evidence for DLE protecting against nephritis in patients with SLE, Dr. Pons-Estel said. He pointed to a study published in 2012 of a multiethnic cohort of patients with SLE in which the authors found that patients with DLE were less likely to have severe renal involvement or end-stage renal disease (ESRD) (Arthritis Care Res. 2012;64:704-12). On the other hand, a 2013 study of 1,043 patients, 117 of whom had DLE, found no association, either positive or negative, between DLE and either lupus nephritis or ESRD (J. Am. Acad. Dermatol. 2013;69:19-24).

To further explore a possible link between time of DLE onset and risk for lupus nephritis, the investigators looked at a sample of patients with SLE from 34 centers in nine Central and South American nations.

They defined lupus nephritis as at least one of the following: proteinuria on two or more occasions or the presence of cellular casts; renal biopsy compatible with lupus nephritis histopathology class II-IV according to World Health Organization criteria; serum creatinine greater than 2.0 mg/dL; and/or ESRD.

The main predictor in the study was DLE onset, and the investigators also included in their multivariate models the potential confounding variables of sex, ethnicity, socioeconomic status, delay in diagnosis, insurance status, and level of education. They also analyzed the contribution of potential clinical confounding variables that included disease activity as assessed by the SLE Disease Activity Index, Systemic Lupus International Collaborating Clinics/ACR Damage Index, and medications such as antimalarial agents, immunosuppressants, methylprednisolone pulse, and oral glucocorticoids at doses greater than 60 mg per day.

In Cox univariate analysis, the only factors significantly associated with lower risk for lupus nephritis included DLE onset before SLE diagnosis (hazard ratio [HR], 0.37; P = .0007), age at diagnosis (HR, 0.91; P = .0013), and years of education (HR, 0.91; P = .0360).

In multivariate proportional regression analysis, the only significant predictors for lower risk were DLE onset in combination with either sociodemographic confounders (HR, 0.37; P = .0008), treatment confounders (HR, 0.37; P = .0009), or clinical disease activity assessments (HR, 0.37; P = .0007).

The association held up in a final prediction multivariate model in which the investigators controlled for sociodemographics, age at diagnosis, ethnicity (Caucasian vs. other), and clinical assessment at diagnosis. In this model, the HR for DLE onset was 0.36 (P = .0006; 98.2% reliability).

The cumulative incidence of lupus nephritis at 1 and 5 years for patients with DLE at or before SLE diagnosis were 7% and 16%, respectively, compared with 16% and 37% for patients with no DLE at diagnosis.

Dr. Pons-Estel acknowledged that the study was limited by a lack of data on skin activity and extension of dermatologic lesions and by missing information on lupus nephritis class for more than two-thirds of patients with the condition.

“Our data point out the need for investigations to unravel immune and environmental factors implicated in the pathways associated with the protective role of DLE onset against lupus nephritis,” he said.

Session co-moderator Dr. Cynthia Aranow, a rheumatologist at the Feinstein Institute for Medical Research in Manhasset, N.Y., who was not involved in the study, questioned whether the protective effective seen with DLE could have come from the antimalarial agent hydroxychloroquine, and whether patients with DLE might be more compliant with the medication.

Dr. Ponss-Estel replied that more than 75% of the patients in the study used an antimalarial agent, but that the investigators found no significant differences in nephritis between patients with DLE who were taking hydroxychloroquine and those who were not.

The study was funded by member institutions. Dr. Pons-Estel and Dr. Aranow reported having no relevant disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial disclosures.

PHILADELPHIA – Renal biopsies are a useful tool for optimizing outcomes in pregnant patients with active lupus nephritis, according to Dr. Derek M. Fine.

Although caution is advisable, a general aversion to biopsying pregnant patients is unwarranted, Dr. Fine of Johns Hopkins University, Baltimore, said at the meeting, sponsored by the American Society of Nephrology.

An important question to ask yourself when deciding if a biopsy should be performed is whether without it you will really know what you are treating.

“For me, it’s very, very scary to take care of a lupus patient when I don’t know what’s going on,” said Dr. Fine, director of the Nephrology Fellowship Program at Johns Hopkins.

Other important questions include whether findings on biopsy will change your management, and whether prior histopathology can help you identify the current problem.

“I would say if it was in the previous few months, yes it’s going to be useful. But once you’re 6 months or a year out, you don’t know what’s going on,” he said, noting that while an educated guess can be made that something similar is going on, one can’t rely on prior histopathology in such cases.

“I’m not saying do it with reckless abandon, but think about doing a biopsy,” he said.

An important benefit of performing a biopsy is disease classification to guide management. Another is differential diagnosis, he said, noting that between 20% and 50% of lupus patients have antiphospholipid antibodies, and that a biopsy can also detect thrombi in the kidney, differentiate preeclampsia if there’s a question about that, and identify focal segmental glomerulosclerosis, which is not an uncommon diagnosis on biopsy in African American patients.

As for the risks of biopsying a pregnant patient, the data are sparse – the largest available study was conducted 27 years ago – but they suggest that complication rates with biopsy during pregnancy are low, and that fetal loss is extremely unusual.

Concerns about preterm labor are often cited as a reason to avoid biopsy, but kidney biopsies are not particularly stress inducing. Bleeding is a concern, but bleeding risk has declined over time, and the procedure has become safer with the use of real-time ultrasound and smaller-gauge needles.

“Doppler technology can tell me there is a bleed, often right away, and interventional radiology availability, compared with 1987, is significant. It was really in its infancy back then, but now to get an angiogram is pretty easy and I can get it done within an hour of doing a kidney biopsy,” he said.

Furthermore, pregnant patients tend to have improved coagulation, and thus reduced bleeding risk, although increased renal blood flow may counteract some of that benefit.

In one study, he and his colleagues found that the risk of bleeding was not much different in lupus and nonlupus patients, at about 2.7%, and the risk was reduced by 50% among those with platelet counts greater than 100,000/mm³, he said.

However, the complication rate seen in patients who undergo biopsy is not insignificant, and these patients should be monitored extremely closely after the procedure.

“It’s a low risk, but a real one,” he said.

The literature documents biopsies performed at up to 32 weeks’ gestation, but biopsy may not be worthwhile later in pregnancy when empiric therapy is more reasonable because of a shorter course, and because the fetus is more viable, he said.

Also, if a bleeding event requiring an angiogram occurs, it is easiest to shield the fetus with lead up to about 24 weeks’ gestation. After that point, it can be more difficult to shield the fetus because of positioning, and this should be taken into consideration.

“I get a little bit nervous doing a kidney biopsy beyond 24 weeks, mainly for this reason,” he said.

If necessary, however, a biopsy can be performed up to 28 weeks’ gestation, he added.

Keep in mind that histopathology cannot be predicted based on clinical features alone. “We really need to get tissue to know what we’re treating,” he said, describing patients with similar clinical features, but different histopathology as an example of why biopsy is important.

A one-size-fits-all approach to treatment doesn’t work under these circumstances; biopsy can help spare patients unnecessary or dangerous treatments, and can help optimize treatment to improve outcomes, he said.

He recommended doing a biopsy for proteinuria of 500 mg/dL or more, avoiding biopsy beyond 28 weeks’ gestation, minimizing bleeding risk, and – from a medicolegal standpoint – ensuring fetal well-being before biopsy to ensure that the biopsy is not blamed for fetal death.

If a biopsy is not possible, make an educated guess as to what you think is going on, and treat accordingly, he said.

“The consensus is that active disease is bad for both fetal and maternal outcomes, and that pregnancy makes lupus worse,” he said, noting that studies have shown that only about 10% of women with active disease achieve a term pregnancy, more than half have a preterm birth, and more than a third experience fetal loss.

Ideally, disease activity would be optimized prior to pregnancy in a patient with lupus, as outcomes are vastly improved by a quiescent disease state, but when this is not successful or possible and a patient presents with pregnancy and active disease, a biopsy should be considered, he said.

Dr. Fine said he had no relevant financial 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 – 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.