Simvastatin in nephrotic syndrome

Background. Hyperlipidemia of the nephrotic syndrome is a risk factor for t he development of systemic atherosclerosis, but it also may aggravate glome rulosclerosis and enhance the progression of glomerular disease. HMG-CoA re ductase inhibitors are effective in reducing cardiovascular morbiditiy and mortality. Whether they may influence the progression of glomerular disease is not clear. The Simvastatin in Nephrotic Syndrome Study addressed the qu estion of whether or not cholesterol lowering by the HMG-CoA reductase inhi bitor simvastatin was superior to placebo treatment in limiting the decline of GFR and reducing proteinuria in nephrotic patients with primary glomeru lonephritis. Methods. This was a prospective, two-year, double-blind trial that included 56 patients with primary glomerulonephritis, hypercholesterolemia due to t he nephrotic syndrome (proteinuria >3 g/24 hr), and a creatinine clearance >40 ml/min/1.73 m(2). They were randomly assigned to treatment with simvast atin or placebo targeted to achieve low density lipoprotein (LDL) cholester ol levels below 120 mg/dl. The objectives were to determine the efficacy an d safety of simvastatin, the rate of GFR decline as measured by inulin clea rance. and the change in proteinuria over a two-year treatment period. Results. Simvastatin produced a mean change in cholesterol, LDL cholesterol , high density lipoprotein (HDL) cholesterol and triglycerides of -39%, -47 %, +1%, and -30%, respectively. Serum lipoprotein(a) [Lp(a)] was not affect ed. No major simvastatin related events occurred. Minor events included ele vations in serum creatine kinase without clinical symptoms. The course of r enal function and of proteinuria during the study are still under evaluatio n and are not given here. Conclusions Long-term treatment with simvastatin in nephrotic patients with hypercholesterolemia is effective and safe.