Effect of LDL Cholesterol and Treatment With Losartan on End-Stage Renal Disease in the RENAAL Study

Abstract

Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/ proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol levels and treatment with losartan on end-stage renal disease (ESRD). Lipid levels and albuminuria measurements were obtained at baseline and at year 1 in a post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, which compared the effects of losartan-versus placebobased antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria. Diabetes Care 31:445-447, 2008A pproximately 60% of patients with chronic kidney disease (CKD) have dyslipidemia (1,2). Elevated LDL cholesterol may be associated with CKD progression (2); however, patients with normal renal function and dyslipidemia do not develop renal insufficiency (3). Treatments that reduce albuminuria and slow CKD progression commonly lower lipids. It is unclear whether lipid lowering itself, rather than as a result of reduced albuminuria, slows CKD progression.We investigated the relationship of LDL cholesterol and albuminuria at baseline and/or year 1 and treatment with losartan on end-stage renal disease (ESRD) in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study. RESEARCH DESIGN AND METHODS -The RENAAL study evaluated losartan-versus placebo-based therapy in 1,513 patients with type 2 diabetes and nephropathy (4). This post hoc analysis included LDL cholesterol (5) and albuminuria measurements at baseline and year 1 before ESRD. Patients were encouraged to control protein and salt intake, but there were no instructions regarding lipid management.Changes from baseline to year 1 are reported as the absolute difference for LDL cholesterol and as the percentage of change in the geometric mean ratio for albuminuria. Stratification for LDL cholesterol at baseline (Ͻ2.59, Ͼ2.59 to Յ3.10, Ͼ3.10 to Յ3.62, Ͼ3.62 to Յ4.14, Ͼ4.14 to Յ4.65, and Ͼ4.65 mmol/l) was based on clinical judgment and sample size/stratum. Event rates were calculated as number of endpoints per 1,000 patient-years of follow-up. Cox regression models were used to calculate hazard ratios (HRs), 95% CIs, and P values with LDL cholesterol Ͻ2.59 mmol/l as reference with/without adjustments for baseline albuminuria (log transformed), serum creatinine, serum albumin, and hemoglobin (6) and with/without additional adjustment for albuminuria at year 1. Similar analyses were done when treatment group was incorporated into the model with the placebo-administered LDL cholesterol increase group as reference. Change in albuminuria by group and by LDL cholesterol Ͻ and Ն3.10 mmol/l was assessed with adjustment for baseline albuminuria (log transformed), ...

Add-On Benefits of Amlodipine and Thiazide in Nondiabetic Chronic Kidney Disease Stage 1/2 Patients Treated with Valsartan

“…This might be due to the lipid-lowering effects of the valsartan plus amlodipine therapy observed in the present study. Since lowering serum LDL levels was positively associated with the reduction in albuminuria [19] , addon amlodipine therapy could decrease UAE to a level similar to add-on hydrochlorothiazide therapy in the patients treated with valsartan. This was also supported by the ANCOVA analysis showing that the decrease in plasma TC level with valsartan plus amlodipine therapy significantly contributed to the decrease in UAE.…”

Renoprotective Effect of Losartan Versus Enalapril in Children with Chronic Kidney Disease

“…Regarding 24hrs urinary proteins, statistically significant differences were found among studied patients, with 76.7% reduction in losartan group and 45.6 % reduction in enalapril group than which was only 4% reduction in non treated group .This result came in agreement withWebb et al [14] study which reported sustained reduction of proteinuria in losartan group and in enalapril group after 3 years of follow-up, and losartan was comparable in terms of efficacy and safety to enalapril.Also with Wuhl et al [16] studywhich reported that there is significant reduction from baseline proteinuria in both enalapril group and losartan group after 6 months of treatment. Also with Ellis et al [17] study which demonstrated that protein excretion decreased after a mean period of 1.9 months with maximal and sustained decrease in proteinuria occurred after a mean of 4.7 months after starting losartan and with Web et al [7] study which reported that losartan significantly reduce proteinuria as compared to amlodipine or placebo.…”

The renal protective effect of angiotensin receptor blockers depends on intra‐individual response variation in multiple risk markers

“…This post hoc analysis focuses on the response to multiple markers including systolic blood pressure (SBP), albuminuria, serum potassium, haemoglobin, total cholesterol and uric acid. These markers were selected since prior studies have shown that intervention in the RAAS can affect these risk marker levels when compared with placebo . Uric acid was not included in the analysis for the IDNT and IRMA‐2 trials, as it was previously shown that irbesartan does not affect this risk marker .…”

“…However, blood pressure is not the only risk marker that is influenced by intervention in the RAAS. Intervention in the RAAS has a broad spectrum of effects on other renal risk markers including decreasing albuminuria, haemoglobin, uric acid, cholesterol and increasing potassium . Changes in these renal risk markers have implications for patients’ clinical prognosis.…”