Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects. In addition, oxalate-induced p38 phosphorylation was significantly attenuated by chloroquine pretreatment but was markedly enhanced by rapamycin pretreatment, whereas the protective effect of chloroquine on rat renal tubular cell oxidative injury was partly reversed by a p38 protein kinase activator anisomycin. Furthermore, the knockdown of Beclin1 represented similar effects to chloroquine on oxalate-induced cell oxidative injury and p38 phosphorylation in vitro. Taken together, our results revealed that autophagy inhibition could attenuate oxalate-induced oxidative injury of renal tubular cell and CaOx crystal depositions in the rat kidney via, at least in part, inhibiting the activation of p38 signaling pathway, thus representing a novel role of autophagy in the regulation of oxalate-induced renal oxidative injury and CaOx crystal depositions for the first time.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and is frequently accompanied by the genetic features of von Hippel–Lindau (VHL) loss. VHL loss increases the expression of hypoxia-inducible factors (HIFs) and their targets, including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF). The primary treatment for metastatic RCC (mRCC) is molecular-targeted therapy, especially anti-angiogenic therapy. VEGF monoclonal antibodies and VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are the main drugs used in anti-angiogenic therapy. However, crosstalk between VEGFR and other tyrosine kinase or downstream pathways produce resistance to TKI treatment, and the multi-target inhibitors, HIF inhibitors or combination strategies are promising strategies for mRCC. HIFs are upstream of the crosstalk between the growth factors, and these factors may regulate the expression of VEGR, EGF, PDGF and other growth factors. The frequent VHL loss in ccRCC increases HIF expression, and HIFs may be an ideal candidate to overcome the TKI resistance. The combination of HIF inhibitors and immune checkpoint inhibitors is also anticipated. Various clinical trials of programmed cell death protein 1 inhibitors are planned. The present study reviews the effects of current and potential TKIs on mRCC, with a focus on VEGF/VEGFR and other targets for mRCC therapy.

The debate still rages on for the usefulness of ureteral access sheath (UAS). Therefore, a meta-analysis to discuss the effects of applying UAS during ureteroscopy was performed. The protocol for the review is available on PROSPERO (CRD42017052327). A literature search was conducted up to November, 2017 using the Web of science, PUBMED, EMBASE and Cochrane Library. The quality of articles was assessed by the Jadad scale and Newcastle Ottawa Scale (NOS). Egger’s test and the trim-and-fill method were used to evaluate publication bias. Effect sizes were calculated by pooled odds ratio (ORs) and mean differences (MDs). Sensitivity analyses and subgroup analyses were performed to explore the origin of heterogeneity. Eight trials with a total of 3099 patients and 3127 procedures were identified. Results showed no significant difference in stone-free rate (SFR) (OR = 0.83, 95% CI 0.52–1.33, P = 0.45), intraoperative complications (OR = 1.16, 95% CI 0.81–7.69, P = 0.88), operative time (MD = 4.09, 95% CI -15.08–23.26, P = 0.68) and hospitalization duration (MD = -0.13, 95% CI -0.32–0.06, P = 0.18). However, the incidence of postoperative complications was higher in UAS group (OR = 1.46, 95% CI 1.06–2.00, P = 0.02). Evidence from meta-analysis indicated that the use of UAS during ureteroscopy did not manifest advantages. However, given the intrinsic restrictions of the quality of selected articles, more randomized controlled trials (RCTs) are warranted to update the findings of this analysis.