Long-term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study)

INTRODUCTION: Low-grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients.

METHODS: Adult HD patients were randomized for double-blind treatment with the ARB irbesartan 150-300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, IL-8, IL-18, and transforming growth factor-β (TGF-β) were measured using Luminex and enzyme-linked immunosorbent assay (ELISA) technology.

FINDINGS: Eighty-two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2-23.4)/2.7(0.2-29.6) μg/mL; IL-1β 1.1(0.0-45.9)/1.1(0.0-7.2) pg/mL; IL-6 10(1-90)/12(1-84) pg/mL; IL-8 31(9-134)/34(5-192) pg/mL; IL-18 364(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between placebo and ARB-treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL-1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL-18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB-treated (P ≥ 0.51 in tests for parallel curves and equal levels).

DISCUSSION: Inflammatory biomarkers were neither acutely, nor in the long-term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti-inflammatory effects.