Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis – a randomized cross-over study

摘要

Background Endothelial dysfunction occurs in patients with end-stage renal disease (ESRD) and is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) contributes to endothelial dysfunction in ESRD. In the general population, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) decrease ADMA levels, but no study has compared the effect of these drugs in patients with ESRD on maintenance hemodialysis (MHD). Methods We evaluated the effect of 1-week treatment with ramipril (5?mg/d), valsartan (160?mg/d), and placebo on ADMA levels in 15 patients on MHD in a double-blind, placebo-controlled, three x three cross-over study. Results We found that ADMA levels were increased at baseline and throughout the dialysis session during ramipril treatment (p? Conclusion These data indicate that short-term ACE inhibition increases ADMA in patients on MHD whereas ARBs do not. In vitro studies further suggest that this may occur through BK-mediated increase in ADMA production during ACE inhibition. Trial registration Clinicaltrials.gov NCT00732069 August 6 2008 and NCT00607672 February 4 2008