BACKGROUND AND OBJECTIVES: This open, prospective, randomized trial aimed to assess the effects of statins in chronic kidney disease patients on optimized antiproteinuric treatment with combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: After 1-month benazepril therapy followed by 1-month benazepril-valsartan combined therapy (run-in), 186 consenting patients with residual proteinuria >0.5 g/24 h were randomized to 6-month benazepril-valsartan therapy alone or combined with fluvastatin. Between-groups changes in proteinuria (primary outcome), serum lipids, and GFR were compared by ANCOVA. Analyses were blinded and by intention to treat. RESULTS: During the run-in, proteinuria decreased more on benazepril-valsartan than on benazepril alone. Proteinuria reduction correlated with concomitant reduction in total, LDL, and HDL cholesterol, and apolipoprotein B and apolipoprotein A levels. After randomization, median proteinuria similarly decreased from 1.2 (0.6 to 2.2) to 1.1 (0.5 to 1.7) g/24 h on fluvastatin and from 1.5 (0.8 to 2.7) to 1.0 (0.5 to 2.4) g/24 h on benazapril-valsartan therapy alone. Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B versus benazepril-valsartan alone, but did not affect serum triglycerides and GFR. Treatment was well tolerated. CONCLUSIONS: In chronic kidney disease patients with residual proteinuria despite combined angiotensin-converting enzyme inhibitor and angiotensin receptor blockade therapy, add-on fluvastatin does not affect urinary proteins, but further reduces serum lipids and is safe. Whether combined angiotensin-converting enzyme inhibitor, angiotensin receptor blockade, and statin therapy may improve cardiovascular outcomes in this high-risk population is worth investigating.
EFFECTS OF ADD-ON FLUVASTATIN THERAPY IN PATIENTS WITH CHRONIC PROTEINURIC NEPHROPATHY ON DUAL RENIN-ANGIOTENSIN SYSTEM BLOCKADE: THE ESPLANADE TRIAL / P. Ruggenenti; A. Perna; M. Tonelli; G. Loriga; N. Motterlini; N. Rubis; F. Ledda; S. Rota Jr; A. Satta; A. Granata; G. Battaglia; F. Cambareri; S. David; F. Gaspari; N. Stucchi; S. Carminati; B. Ene-Iordache; P. Cravedi; G. Remuzzi. - In: CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY. - ISSN 1555-905X. - 5(2010), pp. 1928-1938. [10.2215/CJN.03380410]