Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open‐label, controlled phase II clinical trial

BACKGROUND: This was a randomized, open‐label, controlled phase II clinical trial to investigate the safety, efficacy, and outcomes of intrarenal artery infusion of autologous peripheral‐blood‐derived CD34+ cells for patients with chronic kidney disease (CKD; ie, stage III or IV). MATERIALS AND METHODS: Between October 2016 and July 2018, 52 consecutive patients with CKD at stage III or IV were randomly allocated into a treatment group (TG; 2.5 × 10(7) cells for each intrarenal artery; n = 26) and a control group (CG; standardized pharmacotherapy only; n = 26). The primary endpoints included safety and change of creatinine level/creatinine clearance. The secondary endpoints were 12‐month combined unfavorable clinical outcomes (defined as dialysis or death), improvement in proteinuria, and CD34+ cell‐related adverse events. RESULTS: All patients were uneventfully discharged after CD34+ cell therapy. The baseline endothelial progenitor cell (EPC) populations did not differ between TG and CG (P > .5). Flow cytometric analysis showed increases in circulating EPC (ie, CD34+KDR+CD45(dim)/ CD34+CD133+CD45(dim)/CD31+CD133+CD45(dim)/CD34+CD133+KDR+/CD133+) and hematopoietic stem cell (CD34+) populations after granulocyte‐colony stimulating factor treatment (all P < .001). Besides, Matrigel assay of angiogenesis was also significantly enhanced (all P < .001). Renal‐venous blood samplings (ie, at 0, 5, 10, and 30 minutes after CD34+ cell infusion) demonstrated significant progressive increases in EPC level (P for trend <.001) among the TG patients. One‐year combined unfavorable clinical outcomes were significantly lower in TG than those in CG (0% [0] vs 13.3% [4], P = .038). By 12 months after CD34+ cell therapy, circulating creatinine level, ratio of urine protein to urine creatinine, and creatinine clearance showed no difference between TG and CG (all P > .1). CONCLUSION: CD34+ cell therapy was safe and improved 1‐year outcome.