Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Patients with CKD Stages 3-4: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Patients with chronic kidney disease (CKD) stages 3-4 face progressive renal decline without effective treatments. Human umbilical cord-derived mesenchymal stem cells(UC-MSCs), with potential anti-inflammatory, anti-fibrotic, and reparative properties, may offer a new therapeutic approach. This study assesses UC-MSCs' efficacy and safety in slowing renal function decline in CKD 3-4 patients. Methods: This single-center, randomized, double-blind, placebo-controlled trial enrolled CKD stages 3-4 patients on standard therapy(NCT05512988). Participants were randomized to receive either UC-MSCs (1×10^6 cells/kg/dose, biweekly, 2 doses; n=9) or placebo (n=10). Follow-up occurred at baseline, post-first treatment, and 1, 3, 6, 9, and 12 months post-second treatment. The primary endpoint was a ≥30% GFR decline, ESRD progression, or renal replacement therapy within 12 months. Secondary endpoints included serious adverse events. Results: Among 19 participants (12 females), mean ages were 39.9 (UC-MSCs) and 45.1 years (placebo), with baseline GFR of 42.0±11.9 and 40.4±9.6 mL/min, respectively. Compared to the placebo group (n=7), the UC-MSCs group (n=8) demonstrated greater improvements in GFR from baseline at both 6 months (1.5±6.8 vs -0.4±4.8 mL/min) and 12 months (6.8±12.8 vs 2.4±3.6 mL/min), though these differences did not reach statistical significance. The placebo group showed rising 24-hour urinary albumin levels over time, while the UC-MSCs group remained stable. At 9 months, the UC-MSCs group demonstrated significantly less increase versus controls (P=0.0386). The UC-MSCs group showed superior renal function preservation, with cystatin C changes significantly favoring treatment at both 6 months (P=0.011) and 9 months (P=0.03). The analysis of UC-MSCs effects on inflammatory cells revealed that UC-MSCs maintained stable NK cell counts, while placebo showed significant reduction, with between-group differences at 6 months (P=0.048) and 12 months (P=0.043) The intervention demonstrated acceptable safety, with non-significantly lower adverse events in the cell therapy group (20.0%) versus controls (30.0%) and absence of SAEs. Conclusion: Cell infusion therapy demonstrates safety and potential efficacy in decelerating renal function progression in patients with stage 3-4 CKD.