Cell-based therapies for experimental chronic kidney disease: a systematic review and meta-analysis

Abstract

Abstract Cell-based therapy is a promising strategy for treating chronic kidney disease (CKD) and currently the focus of preclinical studies. We performed a systematic review and meta-analysis to evaluate efficacy of cell-based therapy in preclinical (animal) studies of CKD, and determined factors affecting cell-based therapy efficacy in order to guide future clinical trials. 71 articles met inclusion criteria. Standardized mean differences (SMD) and 95% confidence interval (CI) were calculated for outcome parameters including plasma urea, plasma creatinine, urinary protein, blood pressure, glomerular filtration rate, glomerulosclerosis and interstitial fibrosis. Sub-analysis for each outcome measure was performed for model-related (species, gender, model and timing of therapy) and cell-related (cell type, -condition, -origin, administration route and regime of therapy) factors. Overall, meta-analysis showed that cell-based therapy reduced development and progression of CKD. This was most prominent for urinary protein (SMD 1.34 95% CI [1.00-1.68]) and urea (1.09, 0.66-1.51), both p<0.001. Changes in plasma urea associated with changes in both glomerulosclerosis and interstitial fibrosis. Sub-analysis showed that cell type (bone marrow derived progenitors and mesenchymal stromal cells being most effective) and administration route (intravenous or renal artery injection) were significant predictors of therapeutic efficacy. Timing of therapy in relation to clinical manifestation of disease, and cell-origin and -dose, were not associated with efficacy. Our meta-analysis confirms that cell-based therapies improve impaired renal function and morphology in preclinical models of CKD. Our analyses can be used to optimize experimental interventions and thus support both improved preclinical research and development of cell-based therapeutic interventions in clinical setting.