Comparative effects of angiotensin-converting enzyme inhibition and angiotensin-receptor blockade on inflammation during hemodialysis

Abstract

Biomarkers of oxidative stress and inflammation predict cardiovascular events in maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the general population, but their benefit in maintenance hemodialysis patients is not fully explored. To test whether ACE inhibitors and ARBs differentially affect markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis, we conducted a randomized, double-blind, placebo-controlled 3×3 crossover study. We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks in between the treatments. On the morning of the seventh day of drug treatment, participants underwent serial blood sampling during hemodialysis. Neither ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL-1β concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04) compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis (P<0.01 for each compared with placebo). Valsartan increased F(2)-isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan and ramipril both lowered D-dimer levels (P<0.01 for both), whereas only ramipril seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction as measured by levels of vWf. A prospective clinical trial is necessary to determine whether ACE inhibitors and ARBs also differ with respect to their effects on cardiovascular mortality in this population.

Figures

Figure 1.

Effect of hemodialysis and study interventions on hemodynamic parameters. Changes in MABP (A) and heart rate (B) are depicted during hemodialysis after 1-week treatment with ramipril, valsartan, and placebo.

Figure 2.

Effect of hemodialysis and study interventions on the renin-angiotensin-aldosterone system and bradykinin levels. Plasma ACE activity (A), PRA (B), and bradykinin (C) concentrations are depicted during hemodialysis after 1-week treatment with ramipril, valsartan, and placebo.

Figure 3.

Effect of 1-week treatment with ramipril, valsartan, and placebo on markers of inflammation and oxidative stress in response to hemodialysis.

Figure 4.

Effect of 1-week treatment with ramipril, valsartan, and placebo on markers of coagulation, fibrinolysis, and endothelial function during hemodialysis.

Figure 5.

Randomized double blind 3×3 crossover study. Doses are specified in the text.