Synergistic effects of asymmetrical dimethyl-L-arginine accumulation and endothelial progenitor cell deficiency on renal function decline during a 2-year follow-up in stable angina

Abstract

Background. Renal insufficiency predisposes to coronary artery disease (CAD), but also CAD and traditional risk factors accelerate renal function loss. Endothelial progenitor cell (EPC) deficiency and elevated asymmetrical dimethyl-l-arginine (ADMA), an endogenous nitric oxide (NO) formation inhibitor, predict adverse CAD outcome. Our aim was to assess changes in estimated glomerular filtration rate over time (ΔeGFR) in relation to baseline EPC blood counts and ADMA levels in stable angina.Methods. Eighty non-diabetic men with stable angina were followed up for 2 years after elective coronary angioplasty. Exclusion criteria included heart failure, left ventricular systolic dysfunction, eGFR <30 mlmin1.73 m2 and coexistent diseases. Those with cardiovascular events or ejection fraction <55 during the follow-up were also excluded. A baseline blood count of CD34+kinase-insert domain receptor (KDR)+ cells, a leukocyte subpopulation enriched for EPC, was quantified by flow cytometry (percentage of lymphocytes).Results. A synergistic interaction (P = 0.015) between decreased CD34+KDR+ cell counts and increased plasma ADMA, but not symmetrical dimethyl-l-arginine, was the sole significant multivariate ΔeGFR predictor irrespective of baseline eGFR. ΔeGFR was depressed in the simultaneous presence of high ADMA (>0.45 μmoll, median) and low CD34+KDR+ cell counts (<0.035, median) compared to either of the other subgroups (P = 0.001-0.01). ΔeGFR did not correlate with traditional risk factors, angiographic CAD extent, levels of C-reactive protein and soluble vascular cell adhesion molecule-1.Conclusions. Elevated ADMA and EPC deficiency may synergistically contribute to accelerated renal function decline in stable angina. This could result from the impairment of the EPC-dependent endothelial renewal in the kidney, an NO-dependent process. © The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.