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.

Trial registration: ClinicalTrials.gov NCT00199927.

Figure 1.

Study profile.

Figure 2.

Changes in proteinuria (upper panel) and serum lipids (lower panel) achieved by benazepril alone or benazepril combined with valsartan as compared with inclusion. Data are median and interquartile range for urinary proteins and mean ± SEM for serum lipids. UP, urinary proteins; P/C, protein/creatinine ratio; Chol., cholesterol.

Figure 3.

Correlations between change in 24-hour proteinuria on benazepril combined with valsartan versus inclusion and concomitant changes in serum total, LDL, and HDL cholesterol, apolipoproteins A and B, and triglyceride levels.

Figure 4.

Changes in arterial BP (upper panel) and proteinuria (lower panel) achieved by 6-month fluvastatin or non–HMG-CoA reductase inhibitor therapy as compared with inclusion. Data are mean ± SEM for BP and median and interquartile range for urinary proteins. UP, urinary proteins; P/C, protein/creatinine ratio.

Figure 5.

Changes in serum lipids achieved by 6-month fluvastatin therapy or non–HMG-CoA reductase inhibitor therapy. Data are mean ± SEM. Chol., cholesterol; Apo A, apolipoprotein A; Apo B, apolipoprotein B.