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 2 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]) changed 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 associated 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.