RESUMO
Cisplatin is widely employed in tumor chemotherapy, but nephrotoxicity is an unavoidable side effect of cisplatin. Several studies have demonstrated that mesenchymal stromal cells (MSCs) ameliorate cisplatin-induced kidney injury, but the underlying mechanisms are unknown. In this study, the cisplatin-induced kidney injury mouse model was established by subjecting a single intraperitoneal injection with cisplatin. One hour before cisplatin injection, the mice received human bone marrow MSCs (hBM-MSCs) with or without siRNA-transfection, recombinant human tumor necrosis factor (TNF)-α-stimulated gene/protein 6 (rhTSG-6), or PBS through tail vein. In addition, cisplatin-stimulated HK-2 cells were treated with hBM-MSCs or rhTSG-6. hBM-MSCs treatment remarkably ameliorated cisplatin-induced acute and chronic kidney injury, as evidenced by significant reductions in serum creatinine (Scr), blood urea nitrogen (BUN), tubular injury, collagen deposition, α-smooth muscle actin accumulation, as well as inflammatory responses, and by remarkable increased anti-inflammatory factor expression and Treg cells infiltration in renal tissues. Furthermore, we found that only a few hBM-MSCs engrafted into damaged kidney and that the level of human TSG-6 in serum of mice increased significantly following hBM-MSCs administration. Moreover, hBM-MSCs significantly increased the viability of damaged HK-2 cells and decreased the levels of inflammatory cytokines in the culture supernatant. However, knockdown of TSG-6 gene in hBM-MSCs significantly attenuated their beneficial effects in vivo and in vitro. On the contrary, treated with rhTSG-6 achieved similar beneficial effects of hBM-MSCs. Our results indicate that systemic administration of hBM-MSCs alleviate cisplatin-induced acute and chronic kidney injury in part by paracrine TSG-6 secretion.
RESUMO
Background and Objectives: Asymptomatic bacteriuria (ASB) is prevalent in kidney transplant recipients (KTRs) and is hypothesized to heighten the risk of subsequent urinary tract infections (UTIs). Whether antibiotic treatment of ASB in KTRs is beneficial has not been elucidated. Materials and Methods: We carried out a systematic review and meta-analysis of all randomized controlled trials (RCTs) and quasi-RCTs that examined the merits of managing asymptomatic bacteriuria in KTRs. The primary outcomes were rates of symptomatic urinary tract infections (UTIs) and antimicrobial resistance. Results: Five studies encompassing 566 patients were included. No significant difference in symptomatic UTI rates was found between antibiotics and no treatment groups (relative risk (RR) 1.05, 95% confidence interval (CI) = 0.78-1.41), with moderate heterogeneity (I2 = 36%). Antibiotic treatment was found to present an uncertain risk for the development of drug-resistant strains (RR = 1.51, 95% CI = 0.95-2.40, I2 = 0%). In all trials, no significant difference between study arms was demonstrated regarding patient and graft outcomes, such as graft function, graft loss, hospitalization due to UTI, all-cause mortality, or acute rejection. Conclusions: The practice of screening and treating kidney transplant patients for asymptomatic bacteriuria does not curtail the incidence of future symptomatic UTIs, increase antimicrobial resistance, or affect graft outcomes. Whether early treatment of ASB after kidney transplantation (<2 months) is beneficial requires more RCTs.
