Treatment of Hyperlipidemia in the Nephrotic Syndrome: The Effects of Pravastatin Therapy

The hyperlipidemia of the nephrotic syndrome is characterized by an elevation of total cholesterol (TC) and lowdensity lipoprotein cholesterol (LDLC), with a normal or low high-density lipoprotein cholesterol (HDLC), and an increase in triglycerides (TGs) later in the course of the disease. If sustained, this lipid profile probably places these patients at increased risk for cardiovascular disease. Despite extensive trials of diet and drug therapy in patients with primary hyperlipidemias, few such trials exist in patients with the nephrotic syndrome. We conducted a randomized, prospective, double-blind, placebo-controlled trial to investigate the efficacy and safety of pravastatin, the newest cholesterol synthesis inhibitor, in the treatment of the hyperlipidemia of the nephrotic syndrome. After dietary modification was implemented, 13 patients received^pravastatin and eight received placebo. All patients were maintained on a low-fat, low-cholesterol diet for the duration of the trial (24 weeks). The dose of pravastatin was increased from the initial 20 mg/d to 40 mg/d at week 10 or 18 if TC remained elevated (>50th percentile). A bile acid sequestrant was added at week 18 if TC remained elevated and if the patient was already receiving the maximal pravastatin dosage. Dietary modification did not significantly change the lipid profile. Pravastatin (20 mg/d) reduced TC by 22% from a baseline of 301 ± 28 mg/dL (P < 0.05) and LDLC by 28% from a baseline of 222 ± 28 mg/dL (P < 0.05). When used at 40 mg/d (in six patients) no further change in the lipid profile was observed. Pravastatin caused no significant changes in the HDLC fraction (baseline, 44 ± 3 mg/dL) or in TGs (baseline, 221 ± 37 mg/dL). There was, however, a trend for HDLC to increase (8%) and TGs to decrease (19%). Although difficult to evaluate because of poor compliance, bile acid sequestrants (used in six patients) effected no change in the lipid profiles in patients of either group. Placebo baseline TC, LDLC, HDLC and TG values were similar to the pravastatin group and remained unchanged throughout the study. No patient was dropped from the study because of adverse events attributed to the study medication. Renal function and protein excretion were unaffected by pravastatin. Six diabetic patients treated with pravastatin and patients (n = 8) with chronic renal insufficiency (serum creatinine >1.5 mg/dL) had a response to pravastatin similar to that of the other patients. Our results are similar