Extracellular vesicles for acute kidney injury in preclinical rodent models: a meta-analysis

Abstract

Introduction: Extracellular vesicles (EVs), especially stem cell-derived EVs, have emerged as a potential novel therapy for acute kidney injury (AKI). However, their effects remain incompletely understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EVs on AKI in preclinical rodent models. Methods: We searched PubMed, EMBASE, and the Web of Science up to March 2019 to identify studies that reported the treatment effects of EVs in a rodent AKI model. The primary outcome was serum creatinine (Scr) levels. The secondary outcomes were the blood urea nitrogen (BUN) levels, renal injury score, percentage of apoptotic cells, and interleukin (IL)-10 and tumour necrosis factor (TNF)-α levels. Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using RevMan 5.3 and R software. Results: Thirty-one studies (n = 552) satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of Scr (SMD = - 3.71; 95% CI = - 4.32, - 3.10; P < 0.01), BUN (SMD = - 3.68; 95% CI = - 4.42, - 2.94; P < 0.01), and TNF-α (SMD = - 2.65; 95% CI = - 4.98, - 0.32; P < 0.01); the percentage of apoptotic cells (SMD = - 6.25; 95% CI = - 8.10, - 4.39; P < 0.01); and the injury score (SMD = - 3.90; 95% CI = - 5.26, - 2.53; P < 0.01) were significantly decreased in the EV group, and the level of IL-10 (SMD = 2.10; 95% CI = 1.18, 3.02; P < 0.01) was significantly increased. Meanwhile, no significant difference was found between stem cell-derived EVs and stem cells. Conclusion: The present meta-analysis confirmed that EV therapy could improve renal function and the inflammatory response status and reduce cell apoptosis in a preclinical rodent AKI model. This provides important clues for human clinical trials on EVs.