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Improvement of Lipid Abnormalities Associated with Proteinuria Using Fosinopril, an Angiotensin-Converting Enzyme Inhibitor

Taha Keilani, MD; William A. Schlueter, MD; Murray L. Levin, MD; and Daniel C. Batlle, MD
[+] Article and Author Information

From the Lakeside Veterans Affairs Medical Center and Northwestern Memorial Hospital, Northwestern University Medical School, Chicago, Illinois. Requests for Reprints: Daniel C. Batlle, Northwestern University Medical School, Department of Medicine, Division of Nephrology, 303 E. Chicago Avenue, Chicago, IL 60611. Acknowledgments: The authors thank Dr. Angelo M. Scanu for measuring plasma lipoprotein(a). They also thank Ms. Meenakshi Rammohan for her dietary evaluations and Ms. Lori L. Ramey for preparation of the manuscript. Grant Support: Fosinopril sodium and matching placebo tablets were supplied by the Bristol-Myers Squibb Institute for Medical Research (Princeton, New Jersey), which also provided a grant to Northwestern University (Dr. Batlle) to support this study. All the data collected were made available to the Bristol-Myers Squibb Institute throughout the study. The data collection, analysis, and presentation were the primary responsibility of the investigators.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1993;118(4):246-254. doi:10.7326/0003-4819-118-4-199302150-00002
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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.

Figures

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Figure 1.
Urine protein excretion.Upper panel.closed circlesopen circlesPPMiddle panel.Lower panel.

Changes in urine protein excretion throughout the randomized trial. By two-way ANOVA, the change in protein excretion from baseline differed statistically between the fosinopril group ( ) and the placebo group ( ) (between-group, < 0.01; within-group, < 0.001). The effect of fosinopril on mean urine protein excretion, which was reversible when discontinued. The lack of significant effect of placebo on mean urine protein excretion throughout the study.

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Figure 2.
Serum total cholesterol.Upper panel.closed circlesopen circlesPPMiddle panel.Lower panel.

Changes in serum total cholesterol throughout the double-blind phase. By two-way ANOVA, the change in serum total cholesterol from baseline differed statistically between the fosinopril group ( ) and the placebo group ( ) (between-group, < 0.05; within-group, < 0.001). The effect of fosinopril on mean serum total cholesterol, which was reversible when discontinued. The lack of placebo effect on mean serum total cholesterol throughout the study.

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Grahic Jump Location
Figure 3.
The long-term effect of fosinopril (open-label phase) on urine albumin excretion, serum total cholesterol, serum low-density lipoprotein cholesterol, and plasma lipoprotein(a).P

The asterisk denotes a statistically significant change from washout (placebo) phase ( < 0.05).

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