Simvastatin in nephrotic syndrome. Simvastatin in Nephrotic Syndrome Study Group.
BACKGROUND
Hyperlipidemia of the nephrotic syndrome is a risk factor for the development of systemic atherosclerosis, but it also may aggravate glomerulosclerosis and enhance the progression of glomerular disease. HMG-CoA reductase inhibitors are effective in reducing cardiovascular morbidity and mortality. Whether they may influence the progression of glomerular disease is not clear. The Simvastatin in Nephrotic Syndrome Study addressed the question of whether or not cholesterol lowering by the HMG-CoA reductase inhibitor simvastatin was superior to placebo treatment in limiting the decline of GFR and reducing proteinuria in nephrotic patients with primary glomerulonephritis.


METHODS
This was a prospective, two-year, double-blind trial that included 56 patients with primary glomerulonephritis, hypercholesterolemia due to the nephrotic syndrome (proteinuria > 3 g/24 hr), and a creatinine clearance > 40 ml/min/1.73 m2. They were randomly assigned to treatment with simvastatin or placebo targeted to achieve low density lipoprotein (LDL) cholesterol levels below 120 mg/dl. The objectives were to determine the efficacy and safety of simvastatin, the rate of GFR decline as measured by inulin clearance, 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 affected. No major simvastatin related events occurred. Minor events included elevations in serum creatine kinase without clinical symptoms. The course of renal function and of proteinuria during the study are still under evaluation and are not given here.


CONCLUSIONS
Long-term treatment with simvastatin in nephrotic patients with hypercholesterolemia is effective and safe.
Klinik für Nieren- und Hochdruckkrankheiten, Katharinenhospital, Stuttgart, Germany.
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Olbricht
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Wanner
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Thiery
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Basten
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009404:Nephrotic Syndrome / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; D019821:Simvastatin