Kidney Transplantation Substantially Improves Endothelial Progenitor Cell Dysfunction in Patients with End-Stage Renal Disease

Abstract

Endothelial progenitor cells (EPC) are involved in endothelial repair and maintenance. Dysfunction of EPC may contribute to accelerated arteriosclerosis in chronic kidney disease. Kidney transplantation (KTx) improves both survival and endothelial function of dialysis patients. In a prospective study, we tested to which extent KTx changes EPC biology. We studied number and function (migratory activity, adhesion to extracellular matrix proteins and to mature endothelial cells [EC]) of EPC in 20 patients during dialysis and 3, 6, 9 and 12 months after KTx. Twenty-two healthy volunteers served as matched controls. Circulating precursor populations were measured by flow cytometric analysis. Cytokines relevant for EPC mobilization were monitored. Compared to the dialysis state, KTx increased the migration of EPC to approximately 2-fold. Adhesion to fibronectin and to collagen type IV was significantly increased after KTx. An improved adhesion rate of EPC to mature EC was observed. The number of EPC decreased. The amount of precursor populations showed no difference compared to the pretransplant state. Our study shows an improved function of EPC after KTx. This finding indicates an improved potential for endothelial repair which in turn may contribute to enhanced endothelial function and reduced cardiovascular morbidity after KTx.

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

“…Similarly, de Groot et al (21) have shown that EPC numbers in stable adult renal transplant recipients are comparable to those found in healthy subjects. Although, these and our results do not rule out impairment of EPC capacity evident by diminished function but not levels, Herbrig et al (22) have recently demonstrated improved EPC function after transplantation.…”

Progenitor cells and vascular function are impaired in patients with chronic kidney disease

“…However, dialysis sessions, in themselves, were related to reduced EPC levels, and the overall worse condition and (cardiovascular) comorbidity of dialysis patients may have influenced these results. Several studies suggested that reduction of uraemia by kidney transplantation improved EPC numbers and function [11,13]. Furthermore, EPC levels, were related to graft function by some [11,13], but not others [23].…”

Significance of Endothelial Progenitor Cells in Subjects With Diabetes

“…Therefore, it is not surprising that CKD patients have qualitative and quantitative EPC alterations (53). Mechanisms are largely unknown, but uremic toxins may be involved, as both hemodyalisis and kidney transplantation can restore the endogenous EPC pool (54,55). To date, no study has specifically addressed the question of whether nephropathy per se is associated with further EPC reduction and/or impairment in diabetes, but ϳ50% of CKD patients enrolled in EPC studies had diabetes.…”