Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.

Abstract

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.

• Authors: Piero Ruggenenti, Annalisa Perna, Marcello Tonelli, Giacomina Loriga, Nicola Motterlini, Nadia Rubis, Franca Ledda, Stefano Rota Jr, Andrea Satta, Antonio Granata, Giovanni Battaglia, Francesco Cambareri, Salvatore David, Flavio Gaspari, Nadia Stucchi, Sergio Carminati, Bogdan Ene-Iordache, Paolo Cravedi, Giuseppe Remuzzi, ESPLANADE Study Group
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 5 Issue 11 Pg. 1928-38 (Nov 2010) ISSN: 1555-905X [Electronic] United States
• PMID: 20671225 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Benzazepines
• Fatty Acids, Monounsaturated
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Indoles
• Lipids
• Tetrazoles
• Fluvastatin
• Valsartan
• Valine
• benazepril

Topics

• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (adverse effects, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (adverse effects, therapeutic use)
• Benzazepines (adverse effects, therapeutic use)
• Blood Pressure
• Chi-Square Distribution
• Chronic Disease
• Drug Therapy, Combination
• Fatty Acids, Monounsaturated (adverse effects, therapeutic use)
• Female
• Fluvastatin
• Glomerular Filtration Rate
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects, therapeutic use)
• Indoles (adverse effects, therapeutic use)
• Italy
• Kidney Diseases (complications, drug therapy, physiopathology)
• Lipids (blood)
• Male
• Middle Aged
• Prospective Studies
• Proteinuria (drug therapy, etiology, physiopathology)
• Renin-Angiotensin System (drug effects)
• Tetrazoles (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome
• Valine (adverse effects, analogs & derivatives, therapeutic use)
• Valsartan