Molecular Evaluation of Circulating Endothelial Progenitor Cells in Children Undergoing Hemodialysis and After Kidney Transplantation

Abstract

Increased risk of cardiovascular disease in end-stage renal disease (ESRD) has been explained by accelerated atherosclerosis and impaired angiogenesis, in which endothelial progenitor cells (EPC) may play key roles. Circulating cells with endothelial progenitor phenotype have not been evaluated in children with ESRD. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) approach, we measured endothelial-specific and progenitor-associated genes VE-cadherin (VE-C), CD146, CD31, tyrosine-protein kinase receptor (Tie-2), Flk1, CD133, and growth factors promoting EPC function, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and stromal cell-derived factor-1 (SDF-1) in the blood of pediatric patients undergoing hemodialysis and after transplantation. Patients' metabolic parameters were correlated with EPC marker gene levels. Compared with controls, circulating VE-cadherin, CD146, Flk1, VEGF, and EPO RNA levels were decreased in ESRD and normalized in transplanted patients. Levels of VE-cadherin, which were the most significantly reduced in ESRD (p = 0.001) inversely correlated in all of the patient population with serum urea and creatinine concentration, whereas among the ESRD group showed an inverse correlation with diastolic blood pressure (BP), interventricular septum thickness (IVST), and left ventricular mass index. Pediatric ESRD patients may have lower angiogenic potential and increased cardiovascular morbidity, because of decreased expression of circulating endothelial cell specific transcripts. Prospective studies are required to link this expression pattern and its restoration in transplanted patients to cardiovascular outcome.