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.