Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor

Abstract

Objective: To examine whether reducing protein excretion in patients with proteinuric renal disease using an angiotensin-converting enzyme inhibitor, fosinopril sodium, would be accompanied by an amelioration of the associated hyperlipidemia.

Design: A randomized, placebo-controlled, double-blind study of 12 weeks, followed by 23 weeks of an open-label trial using fosinopril.

Setting: Outpatient renal clinics.

Patients: Twenty-six patients (age range, 28 to 70 years) with mild to moderate renal impairment and proteinuria associated with type II diabetes (15 patients) and other causes of nondiabetic renal disease (11 patients) completed the double-blind phase of the study. All patients except one were men.

Intervention: Fosinopril, 10 mg initial oral daily dose (randomized trial), and 20 mg orally once a day (open-label phase).

Measurements: Proteinuria and serum lipids (total cholesterol, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol, and lipoprotein(a) protein).

Results: In a group of 17 patients treated with fosinopril, protein excretion decreased from 5.56 to 4.28 g/d, a reduction of 1.28 (95% CI, -2.49 to -0.08). The reduction was associated with a decrease in serum total cholesterol from 6.39 to 5.82 mmol/L, a decrease of 0.58 mmol/L (CI, -1.01 to -0.15 mmol/L). In a group of nine patients treated with placebo, neither protein excretion (from 5.11 to 4.81 g/d, a change of -0.29 g/d [CI, -1.78 to +1.13 g/d]) nor serum total cholesterol (from 6.08 to 5.77 mmol/L, a change of -0.31 mmol/L [CI, -0.78 to +0.13 mmol/L]) change significantly. At the end of the double-blind phase, plasma lipoprotein(a) protein decreased in the fosinopril-treated group (from 3.94 to 3.33 mg/dL, a reduction of 0.60 mg/dL [CI, -1.02 to -0.18 mg/dL]) but not in the placebo group (from 2.85 to 3.19 mg/dL, a change of +0.34 mg/dL [CI, -0.53 to +1.2 mg/dL]). Dietary protein and fat intake were similar in the two groups throughout the study. In 16 patients who completed an extended open-label phase, fosinopril was associted with a decrease in protein excretion from 4.53 to 3.22 g/d, a reduction of 1.29 g/d (CI, -2.54 to -0.05 g/d), which was associated with a reduction in serum total cholesterol (from 6.37 to 5.54 mmol/L, a decrease of 0.84 mmol/L [CI, -1.59 to -0.08 mmol/L]), LDL cholesterol (from 4.38 to 3.72 mmol/L [a decrease of 0.68 mmol/L [CI, -1.33 to -0.03 mmol/L]), and plasma lipoprotein(a) protein (from 3.58 to 2.81 mg/dL, a reduction of 0.82 mg/dL [CI, -1.58 to -0.05 mg/dL]).

Conclusion: The angiotensin-converting enzyme inhibitor, fosinopril, can result in a sustained reduction in serum total cholesterol, LDL cholesterol, and plasma lipoprotein(a) protein levels in conjunction with a partial reduction in proteinuria.