title: 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.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-2372, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Gamboa
authors.forename: Mias
authors.initials: M
authors.lastname: Pretorius
authors.forename: Deanna R
authors.initials: DR
authors.lastname: Todd-Tzanetos
authors.forename: James M
authors.initials: JM
authors.lastname: Luther
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D023201:CD40 Ligand / Q000097:blood; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017257:Ramipril / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000009:adverse effects*; D012083:Renin / Q000097:blood; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D013777:Tetrazoles; D023201:CD40 Ligand; D000068756:Valsartan; D012083:Renin; D014633:Valine; D017257:Ramipril