A systematic review and meta-analysis of mesenchymal stem cell therapy in diabetic nephropathy and lupus nephritis or proteinuric nephropathy

Diabetic nephropathy and lupus nephritis (LN) or proteinuric nephropathy slow progression but rarely reverse established renal damage. Mesenchymal stromal/stem cell (MSC) therapy has been explored as a regenerative and immunomodulatory approach. To assess the efficacy and safety of MSC therapy in diabetic nephropathy and LN or proteinuric nephropathy. We systematically searched PubMed, the Cochrane Library, and EMBASE up to November 1, 2024. Eligible studies included patients with diabetic nephropathy, LN or proteinuric nephropathy who received MSC therapy, either compared with a placebo/control group or as single-arm cohorts with predefined renal function outcomes. Data extraction was performed in duplicate. The risk of bias was assessed using the Cochrane tool. The primary outcome was the change in estimated glomerular filtration rate (eGFR); safety outcomes focused on serious adverse events (SAEs). Only randomized trials were included in the quantitative synthesis; non-randomized and single-arm studies were described separately. The effect size was expressed as the mean difference (MD), calculated using a random-effects model. Among the included randomized trials, MSC treatment significantly improved eGFR compared with the placebo group (pooled MD = 4.62 mL/min/1.73 m², 95% confidence interval (CI) [1.31, 7.94]; Higgins’ inconsistency statistic (I²) = 27.20%). Across the randomized controlled trials (RCTs) for diabetic kidney disease (DKD), there was no increase in SAEs (pooled relative risk = 1.97, 95% CI [0.65, 5.94]; I² = 0%). The pooled incidence of events from single-arm studies was summarized qualitatively. Six studies (n = 104) met the inclusion criteria: two randomized trials in DKD, one randomized trial in LN, and three single-arm studies. In the pooled analysis of randomized trials, MSC treatment significantly improved the eGFR compared with the placebo group (pooled MD = 4.62 mL/min/1.73 m², 95% CI: 1.31 to 7.94; I² = 27.20%). The single-arm studies were clinically and methodologically heterogeneous. Across the DKD RCTs, there was no significant increase in SAEs (pooled risk ratio [RR] = 1.97, 95% CI: 0.65 to 5.94; I² = 0%). The incidence data from single-arm studies are summarized qualitatively. In this stratified synthesis, MSC therapy showed a consistent signal of benefit for kidney function in DKD randomized trials, with modest eGFR improvement and very low between-study heterogeneity. In LN, evidence remains limited to one small RCT and single-arm studies. Across the DKD RCTs, SAEs were not increased with MSCs, and single-arm cohorts suggested acceptable short-term tolerability, though safety reporting was heterogeneous.