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(Circulation. 2003;107:586.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Diverse Effects of Increasing Lisinopril Doses on Lipid Abnormalities in Chronic Nephropathies

Piero Ruggenenti, MD; Naobumi Mise, MD; Roberto Pisoni, MD; Federica Arnoldi, RN; Anna Pezzotta, Chemist; Annalisa Perna, Stat Sci D; Dario Cattaneo, PharmD; Giuseppe Remuzzi, MD

From the Clinical Research Center for Rare Diseases "Aldo and Cele Daccò" (P.R., N.M., R.P., F.A., A. Pezzotta, A. Perna, D.C., G.R.), Mario Negri Institute, Bergamo, Italy; the Unit of Nephrology and Dialysis (P.R., G.R.), Ospedali Riuniti, Bergamo, Italy; and the Second Department of Internal Medicine (N.M.), University of Tokyo, Japan.

Correspondence to Piero Ruggenenti, MD, Renal Medicine Department, Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11-24125 Bergamo, Italy. E-mail manuelap{at}marionegri.it

Background— Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria.

Methods and Results— In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients.

Conclusions— In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.

Key Words: inhibitors, angiotensin-converting enzyme • nephropathies • proteinuria • dyslipidemia • nephrotic syndrome

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