Rosuvastatin-Induced Arrest in Progression of Renal Disease

Abstract

Preclinical and limited clinical data suggest that statins decrease the progressive decline in renal function that occurs in patients with renal disease. Pooled analysis of data obtained from a population of hyperlipidemic patients enrolled in the rosuvastatin (Crestor^®) clinical development program permitted assessment of its effects on renal function both early and later in the course of treatment. Study participants were initially included in controlled clinical trials that evaluated the lipid-lowering efficacy and safety of rosuvastatin when compared with placebo or other lipid-lowering agents (i.e., atorvastatin, simvastatin, pravastatin, cholestyramine, fenofibrate or extended-release niacin). The median duration of treatment with the various doses of statins in these trials was approximately 8 weeks. Following completion of a controlled clinical trial, patients were permitted to enter an open-label extension trial and received rosuvastatin treatment. These data permitted assessment of renal function in a diverse group of over 10,000 patients who received rosuvastatin in its recommended dose range (5–40 mg) for up to 3.8 years. Mean serum creatinine concentrations were lower when compared with baseline both early and later in the course of rosuvastatin treatment. In contrast, no change in mean serum creatinine was observed with placebo. Mean glomerular filtration rates (GFR) predicted from the Modification of Diet in Renal Disease (MDRD) equation were higher when compared with baseline both early and later in the course of rosuvastatin treatment. No change in GFR was observed in the placebo group. Among patients who received long-term rosuvastatin treatment (≧96 weeks), GFR was unchanged or tended to increase, rather than decrease, when compared with baseline irrespective of age, gender, hypertensive or diabetic status, level of renal function (GFR ≧60 vs. <60 ml/min/1.73 m²) at entry or urine dipstick protein status prior to or during the period of treatment. These findings suggest that rosuvastatin may arrest the progression of renal disease.

Effect of Intensive Lipid Lowering with Atorvastatin on Renal Function in Patients with Coronary Heart Disease

“…The prevalence of CKD in the TNT study was approximately 32% (based on eGFR Ͻ60 ml/min per 1.73 m 2 ), consistent with previous studies of CHD populations (11,29,34,36), illustrating that this is an important and potentially underrecognized condition in patients with CHD. By the end of the study, renal function in participants who had CKD and were treated with 80 mg of atorvastatin had improved by almost 10%, compared with 6.6% in participants who had CKD and were treated with 10 mg of atorvastatin.…”

Inhibitors of HMG-CoA Reductase Reduce Receptor-mediated Endocytosis in Human Kidney Proximal Tubular Cells

“…The proteinuria observed with rosuvastatin was generally transient, not associated with worsening renal function and mainly of tubular type, suggesting reduced reabsorption of normally filtered proteins (7)(8)(9). The observations made in OK cells suggest that the mechanism for a reduced rate of protein reabsorption is linked to inhibition of HMG-CoA reductase in the proximal tubule cells which in turn leads to a depletion of the cellular GGPP pool and thereby to reduced function of one or more GTP-binding proteins, known to be involved in the process of endocytosis (6,10 -12).…”

Complications of Statin Therapy and Their Management

“…26 It is usually transient and has not been associated with worsened renal function. Combined data from 3 trials of pravastatin showed that renal failure or other renal disease designating a serious adverse event occurred in 48 (0.5%) participants allocated pravastatin and 78 (0.8%) allocated placebo.…”