Circulating Endothelial Progenitor Cell Levels Predict Cardiovascular Events in End-Stage Renal Disease Patients on Maintenance Hemodialysis

Abstract

Background: The number of circulating endothelial progenitor cells (EPCs) has been identified as a surrogate biologic marker for vascular function and cumulative cardiovascular (CV) risk in the general population. Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have markedly decreased EPC counts and function. We hypothesized that the number of circulating EPCs predicts death from all causes and CV events in patients with ESRD on HD. Methods: We quantified the EPCs in blood samples from 70 patients with ESRD on HD. Circulating EPCs were counted by flow cytometry as the number of CD45^lowCD34⁺VEGFR2⁺ cells. Death from all causes and CV events served as outcome variables over a median follow-up period of 20 months. Results: It has been postulated that the number of circulating EPCs at baseline ranged from 1 to 350 cells/200 μl, with a mean of ± standard deviation (SD) of 26.0 ± 48.2 cells/200 μl. The median, lowest and highest tertiles of EPC counts were 11.0, 9.0, and 17.0 cells/200 μl, respectively. Patients with the lowest tertile EPC counts had significantly higher rates of CV events, but mortality was similar between the two groups. After adjusting for these risk factors, HbA1c and the lowest tertile EPC count remained as independent predictors of CV events. A cutoff value of 9.5 cells/200 μl maximized the power of the EPC count to predict future CV events as determined by ROC curve analysis. Conclusions: Reduced circulating EPC counts independently predicted CV events in 70 patients with ESRD on maintenance HD. Circulating EPCs may play a role in vascular repair, thereby affecting the clinical course of CV events.

Levels of Circulating Progenitor Cells, Cardiovascular Outcomes and Death

“…[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Characteristics of studies included from meta-analysis are given in the Table. The most important reason whereby studies initially retrieved were finally excluded from meta-analysis was the lack of a poolable risk estimate and impossibility to calculate such estimate from the data provided (Online Table III). Pooled cumulative clinical characteristics of the metaanalyzed patient population are reported in Online Table IV.…”

“…Four of the 21 studies (n=512 patients, 12.8% of the total population) were conducted in patients with acute coronary syndrome, acute myocardial infarction, or stroke. 20,25,27,34 For the remainders, the underlying disease or condition was elective percutaneous intervention in 7 of 17 studies (n=795 patients; 19.1%), [17][18][19]22,29,31,33 elective coronary angiography for suspected coronary artery disease in 2 of 17 (n=1412 patients; 34.0%), 28,32 end-stage renal disease in 4 of 17 studies (n=705 patients; 17.0%), 23,24,26,35 chronic heart failure in 1 of 17 studies (n=156 patients; 3.8%), 16 and aortic stenosis in 1 of 17 study (n=261 patients; 6.3%). 35 One study included patients with and without chronic CVD at baseline, 21 and 1 study included both healthy subjects and patients with chronic or acute CVD.…”

Circulating Progenitor Cells Affect Thrombosis of Dialysis Arteriovenous Fistulas

“…In non-dialysis patients, EPCs have been reported to be associated with vascular events, restenosis after coronary interventions and late stent thrombosis [19,20] . In HD patients, the number and function of EPC is depressed and has been demonstrated to be associated with cardiovascular events [7,8] . Nonetheless, the role of EPCs in the development of AVF thrombosis has not been evaluated.…”

“…Circulating EPCs have been demonstrated to reflect vascular repair capacity and vascular function [6] . In patients with end-stage renal disease (ESRD), both the number and function of EPCs are decreased and the deficiency of EPCs is associated with cardiovascular events and maturation of AVFs [7][8][9][10][11] . However, the relationship between EPCs and AVF thrombosis had not been explored.…”

Traditional, Nontraditional, and Uremia-Related Threats for Cardiovascular Disease in Chronic Kidney Disease

“…Impaired endothelial function is a characteristic of early stages of chronic kidney disease, and multiple possible causes have been identified: (1) reduced clearance of endothelial NO synthase (e-NOS) inhibitor asymmetric dimethylarginine (ADMA), which leads to reduced bioavailability of endothelial NO; (2) activation of angiotensin II, which induces oxidative stress; (3) high levels of homocysteine; (4) chronic inflammation; (5) dyslipidemia and (6) endothelial progenitor cell deficiency [32]. Endothelial dysfunction contributes significantly to the initiation and progression of CVD in CKD.…”