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. (16th April 2020)

• Record Type: Journal Article
• Authors: Yang, Chih-Chao; Sung, Pei-Hsun; Cheng, Ben-Chung; Li, Yi-Chen; Chen, Yi-Ling; Lee, Mel S.; Yip, Hon-Kan
• Is Part Of: Stem cells translational medicine. Volume 9:Number 8(2020)
• Page Start: 827
• Page End: 838
• Publication Date: 2020-04-16
• Subjects: angiogenesis -- CD34+ cell therapy -- chronic kidney disease -- circulating endothelial progenitor cells; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.1002/sctm.19-0409
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: 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. : Abstract : Flowchart illustrating the screening, exclusion, enrollment, assignment, allocation, ?follow-up, and analysis of this phase II clinical trial. CDK, chronic kidney disease; ESRD, ?end-stage? renal disease; HF, heart failure; MI, myocardial infarction.