Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease (CKD) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end‐stage kidney disease (ESKD), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia‐induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia‐inducible signalling pathways and complex interactive networks. Therefore, this review will focus on the signalling pathways involved in hypoxia‐induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF, TGF‐β, Notch, PKC/ERK, PI3K/Akt, NF‐κB, Ang II/ROS and microRNAs. Roles of molecules such as IL‐6, IL‐18, KIM‐1 and ADO are also reviewed. A comprehensive understanding of the roles that these hypoxia‐responsive signalling pathways and molecules play in the context of renal fibrosis will provide a foundation towards revealing the underlying mechanisms of progression of CKD and identifying novel therapeutic targets. In the future, promising new effective therapy against hypoxic effects may be successfully translated into the clinic to alleviate renal fibrosis and inhibit the progression of CKD.

Background: Gut dysbiosis is postulated to participate in the pathogenesis of IgA nephropathy (IgAN). However, the key bacterial taxa closely associated with IgAN onset and treatment response have not been identified. Methods: We recruited 127 patients with IgAN who were treatment naive and 127 matched healthy controls (HCs) who were randomly divided into discovery and validation cohorts to investigate the characteristics of their gut microbiota and establish a bacterial diagnosis model for IgAN. A separate cohort of 56 patients and HCs was investigated to assess crossregional validation. A further 40 patients with primary membranous nephropathy (MN) were enrolled to probe disease-specific validation. A subgroup of 77 patients was prospectively followed to further dissect the association between alterations in gut microbiota and treatment response after 6 months of immunosuppressive therapy. Fecal microbiota samples were collected from all participants and analyzed using 16S ribosomal RNA sequencing. Results: Decreased α-diversity (Shannon, P=0.03), altered microbial composition (Adonis, P=0.0001), and a striking expansion of the taxonomic chain Proteobacteria–Gammaproteobacteria–Enterobacteriales–Enterobacteriaceae–Escherichia-Shigella (all P<0.001) were observed in patients with IgAN who were treatment naive, which reversed only in patients who achieved clinical remission after 6 months of immunosuppressive therapy. Importantly, seven operational taxa units, of which Escherichia-Shigella contributed the most, were determined to be the optimal bacterial classifier of IgAN (AUC=0.8635, 0.8551, 0.8026 in discovery, validation, and cross-regional validation sets, respectively), but did not effectively distinguish patients with IgAN versus those with MN (AUC=0.6183). Bacterial function prediction further verified enrichment of the shigellosis infection pathway in IgAN. Conclusion: Gut dysbiosis, characterized by a striking expansion of genus Escherichia-Shigella, is a hallmark of patients with IgAN and may serve as a promising diagnostic biomarker and therapeutic target for IgAN. Further studies are warranted to investigate the potential contribution of Escherichia-Shigella in IgAN pathogenesis.

Emerging evidence demonstrates that gut dysbiosis is implicated in the pathogenesis of chronic kidney disease (CKD) with underlying mechanisms involving mucosal and/or systematic immunity or metabo...

Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients. We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review. After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD − 65.82 [− 194.19, 62.55]), lactate (MD 0.49 [− 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [− 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD − 0.04 [− 0.13, 0.05]), serum lactate level (MD 0.69 [− 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [− 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h. Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.