Erythropoietin Preconditioning Mobilizes Endothelial Progenitor Cells to Attenuate Nephron-Sparing Surgery-Induced...

The purpose of this study was to examine the role of endothelial progenitor cells (EPCs) in protection against ischemic-reperfusion injury (IRI) in a nephron-sparing surgery (NSS) rat model using erythropoietin (EPO) preconditioning. Fifty-four male Sprague-Dawley rats were randomly divided into 3 groups for right kidney nephrectomy treatment: sham group (exposure without clamp treatment), NSS group (3 days of peritoneal phosphate buffered saline [PBS] injection before renal blood vessels were clamped for 40 mins and NSS was performed), and EPO group (3 days of EPO abdomen injections prior to renal blood vessel clamping for 40 min before NSS was performed). After 12, 24, and 72 hours, inferior vena cava blood and renal tissues were harvested. The extent of renal injury was assessed, along with EPC number, cell proliferation, angiogenesis, and vascular growth factor expression. EPO preconditioning significantly improved renal function and histologic morphology, indicated by reduced blood urea nitrogen (BUN) ([33.12 ± 1.88] vs [16.03 ± 0.91], P < .05) and serum creatinine (Scr) ([190.2 ± 20.23] vs [77.23 ± 5.82], P < .05) levels and histologic injury scores ([3.20 ± 0.78] vs [1.70 ± 0.67], P < .05). Angiogenesis in peritubular capillaries markedly increased in the EPO group. EPC numbers increased in the kidneys at 24 hours following reperfusion in the EPO group, compared to the NSS group. Furthermore, EPO preconditioning also increased SDF-1α and CXCR7 expression at 24 hours following reperfusion relative to the NSS group. These findings suggest that EPO pretreatment can reduce renal injury in rats caused by IRI. Mechanistically, this may be related to EPC mobilization and recruitment to injured renal tissues by SDF-1α and CXCR7.