title: Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or significant proteinuria.
abstract: Experimental evidence suggests that lipid lowering therapy could slow the progression of renal disease in humans. We have conducted a double-blind, placebo controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with the nephrotic syndrome or significant proteinuria (> 1 g/day) and hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid lowering diet for at least 10 weeks before randomization. After a four-week placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10 mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven dropouts, none of whom were "definitely" related to drug therapy. Total and LDL cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001, P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no significant changes in HDL levels. There were no significant differences between the groups in their urine protein levels, their rise in plasma creatinine, or decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for hypercholesterolemia in proteinuric states. A much larger trial is needed to show if potent lipid-lowering therapy slows progression of hypercholesterolemic proteinuric diseases.
authors.affiliation: Department of Nephrology, Royal Free Hospital, London, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Thomas
authors.forename: K P
authors.initials: KP
authors.lastname: Harris
authors.forename: C
authors.initials: C
authors.lastname: Ramaswamy
authors.forename: J M
authors.initials: JM
authors.lastname: Hattersley
authors.forename: D C
authors.initials: DC
authors.lastname: Wheeler
authors.forename: Z
authors.initials: Z
authors.lastname: Varghese
authors.forename: J D
authors.initials: JD
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Walls
authors.forename: J F
authors.initials: JF
authors.lastname: Moorhead
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D007444:Inulin / Q000097:blood; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000150:complications*; D010919:Placebos; D011507:Proteinuria / Q000150:complications*; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010919:Placebos; D014280:Triglycerides; D007444:Inulin; D008148:Lovastatin; D019821:Simvastatin; D003404:Creatinine