Background: The NLRP3 inflammasome is a cytoplasmic polymeric protein complex composed of the cytoplasmic sensor NLRP3, the apoptosis-related spot-like protein ASC, and the inflammatory protease caspase-1. NLRP3 activates and releases IL-1β through classical pathways, and IL-18 mediates inflammation and activates gasdermin-D protein to induce cellular pyroptosis. Numerous studies have also emphasized the non-classical pathway activated by the NLRP3 inflammasome in chronic kidney disease (CKD) and the inflammasome-independent function of NLRP3. Summary: The NLRP3-targeting inflammasome and its associated pathways have thus been widely studied in models of CKD treatment, but no drug that targets NLRP3 has thus far been approved for the treatment of CKD. Key Messages: We herein reviewed the current interventional methods for targeting the NLRP3 inflammasome in various CKD models, analyzed their underlying mechanisms of action, classified and compared them, and discussed the advantages and follow-up directions of various interventional methods. This review therefore provides novel ideas and a reference for the development of targeted NLRP3-inflammasome therapy in CKD.

Objective: Type III Bartter syndrome (BS) is caused by loss-of-function mutations in the gene encoding basolateral chloride channel ClC-Kb (CLCNKB), and is characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here, we investigated the molecular defects in four Chinese children with clinical manifestations of Bartter syndrome. Methods: The genomic DNA of the four patients was screened for gene variations using whole-exome sequencing (WES). The candidate variants were validated by direct Sanger sequencing. Quantitative PCR (qPCR) was subsequently performed to confirm the whole CLCNK gene deletion mutation. A minigene assay and reverse transcription PCR (RT-PCR) were performed to analyze the effect of splice variants in vitro. Results: Our patients showed early onset age with hyponatremia, hypokalemia, hypochloremia, repeated vomiting and growth retardation, suggesting Bartter syndrome. Genetic analysis revealed that all patients carried compound heterozygous or homozygous truncating variants in the CLCNKB gene. In particular, we identified a novel nonsense variant c.239G > A (p.(Trp80*)), two splice site variants (c.1053-1 G > A and c.1228-2A > G), a whole gene deletion, and a novel synonymous variant c.228A > C (p.(Arg76Arg)) which located -2 bp from the 5′ splice donor site in exon 3. Furthermore, our in vitro minigene analysis revealed c.228A > C, c.1053-1G > A, and c.1228-2A > G cause the skipping of exon 3, exon 12, and exon 13, respectively. Conclusion: Our results support that the whole CLCNKB gene deletion is the most common mutation in Chinese patients with type III BS, and truncating and whole gene deletion variants may account for a more severe phenotype of patients. We verified the pathogenic effect of three splicing variants (c.228A > C, c.1053-1G > A, and c.1228-2A > G) which disturbed the normal mRNA splicing, suggesting that splice variants play an important role in the molecular basis of type III BS, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.

Background: Uric acid (UA) has been reported to be an important risk factor for cardiovascular diseases and can cause endothelial cell apoptosis through unclear mechanisms. Accumulating evidence has demonstrated that miR-214 plays a pivotal role in the pathogenesis of cardiovascular diseases. This study was to investigate the role of miR-214 in UA-induced endothelial cell apoptosis and the underlying mechanism. Material and methods: We enrolled 30 patients with hyperuricemia and 32 healthy controls and analyzed the levels of miR-214 in the serum of the participants. Then mouse aorta endothelial cells (MAECs) were treated with UA to induce cell apoptosis. An miR-214 mimic and a specific COX-2 inhibitor (NS398) were used to confirm the roles of these molecules in mediating UA-induced MAEC apoptosis or COX-2/PGE₂ cascade activation. Results: A significant reduction in circulating miR-214 in the hyperuricemia patients compared with the healthy controls, along with a negative correlation with UA levels was observed. In the MAECs, UA treatment strikingly increased apoptosis as shown by the upregulation of BAX and cleaved Caspase-3 and the increased number of apoptotic cells. Interestingly, the expression of COX-2 was also upregulated at both the protein and mRNA levels during UA-induced cell apoptosis. In addition, an miR-214 mimic blocked UA-induced MAEC apoptosis, COX-2 induction and PGE₂ secretion. The inhibition of COX-2 markedly ameliorated UA-induced apoptotic response and PGE₂ production in MAECs. Luciferase activity assays further confirmed that COX-2 is a target gene of miR-214 in endothelial cells. Conclusion: We concluded that miR-214 could alleviate UA-induced MAEC apoptosis possibly by inhibiting the COX-2/PGE₂ cascade.