Journal of The American Society of Nephrology最新文献

{"title":"From Despair to Promise: The Dawn of Novel Treatment in IgA Nephropathy.","authors":"Sydney C W Tang, Girish N Nadkarni","doi":"10.1681/ASN.0000000551","DOIUrl":"https://doi.org/10.1681/ASN.0000000551","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Ravulizumab in IgA Nephropathy: A Phase 2 Randomized Double-Blind Placebo-Controlled Trial.","authors":"Richard Lafayette, James Tumlin, Roberta Fenoglio, Jessica Kaufeld, Miguel Ángel Pérez Valdivia, Mai-Szu Wu, Shih-Han Susan Huang, Eric Alamartine, Sung Gyun Kim, Min Yee, Andreas Kateifides, Kara Rice, Katherine Garlo, Jonathan Barratt","doi":"10.1681/ASN.0000000534","DOIUrl":"10.1681/ASN.0000000534","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Simulation of Hemodialysis Reveals Hemodialysis-Associated Pro-Arrhythmic Effects in a Human Cardiomyocyte Model.","authors":"Thomas Körtl, Niklas Hankowitz, Laura Stengel, Oliver Pfeuffer, Dominic Riedl, Frank Schweda, Katrin Streckfuß-Bömeke, Samuel Sossalla","doi":"10.1681/ASN.0000000563","DOIUrl":"10.1681/ASN.0000000563","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation-Based Sample Size Estimation in Clinical Trials in Nephrology.","authors":"Leila R Zelnick","doi":"10.1681/asn.0000000560","DOIUrl":"https://doi.org/10.1681/asn.0000000560","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"78 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Processes of Care after Acute Kidney Injury.","authors":"L Parker Gregg,David E Leaf","doi":"10.1681/asn.0000000548","DOIUrl":"https://doi.org/10.1681/asn.0000000548","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"119 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GALNT3 in Ischemia-Reperfusion Injury of the Kidney.","authors":"Wenwen Wu,Ying Fu,Honglin Li,Yu Xiang,Yuqing Zeng,Juan Cai,Zheng Dong","doi":"10.1681/asn.0000000530","DOIUrl":"https://doi.org/10.1681/asn.0000000530","url":null,"abstract":"BACKGROUNDDamages to subcellular organelles, such as mitochondria and endoplasmic reticulum, are well-recognized in tubular cell injury and death in acute kidney injury (AKI). However, the changes and involvement of Golgi apparatus are much less known. Here, we report the regulation and role of N-acetylgalactosaminyltransferase-3 (GALNT3), a key enzyme for protein glycosylation in Golgi apparatus, in AKI.METHODSAKI was induced in mice by renal ischemia-reperfusion or cisplatin. In vitro, rat kidney proximal tubular cells were subjected to hypoxia/reoxygenation (H/R) injury. To determine the role of GALNT3, its specific inhibitor T3inh-1 was tested in mice, and the effects of GALNT3 overexpression as well as knockdown were examined in the rat renal proximal tubular cells. EGFR activation was induced by recombinant EGF or by overexpressing EGFR.RESULTSGALNT3 was significantly decreased in both in vivo and in vitro models of AKI induced by renal ischemia-reperfusion and cisplatin. T3Inh-1, a specific GALNT3 inhibitor, exacerbated ischemic AKI and suppressed tubular cell proliferation in mice. Moreover, knockdown of GALNT3 increased apoptosis during H/R treatment in rat renal proximal tubular cells, while overexpression of GALNT3 attenuated H/R-induced apoptosis, further supporting a protective role of GALNT3. Mechanistically, GALNT3 contributed to O-glycosylation of epidermal growth factor receptor (EGFR) and associated EGFR signalling. Activation or overexpression of EGFR suppressed the pro-apoptotic effect of GALNT3 knockdown in H/R-treated rat renal proximal tubular cells.CONCLUSIONSGALNT3 protected kidney tubular cells in AKI at least partially through O-glycosylation of EGFR.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"110 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Physicochemical Approach to Acid-Base Balance: A Critique.","authors":"Man S Oh,Jaime Uribarri","doi":"10.1681/asn.0000000561","DOIUrl":"https://doi.org/10.1681/asn.0000000561","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"44 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Community Care and Access to Follow-Up after Acute Kidney Injury Hospitalization: A Randomized Clinical Trial.","authors":"Neesh Pannu,Kerry A McBrien,Zhi Tan,Nasreen Ahmad,Coralea Bignell,Eleanor Benterud,Taylor Palechuk,Tyrone G Harrison,Braden J Manns,Nairne Scott-Douglas,Matthew T James","doi":"10.1681/asn.0000000537","DOIUrl":"https://doi.org/10.1681/asn.0000000537","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"236 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"I-mfa, Mesangial Cell TRPC1 Channel, and Regulation of Glomerular Filtration Rate.","authors":"Yu Tao,Muyi Liu,Garland Siebert,Paromita Das-Earl,Deena Ibrahim,Nicole Crowe,Suilan Zheng,Rong Ma","doi":"10.1681/asn.0000000533","DOIUrl":"https://doi.org/10.1681/asn.0000000533","url":null,"abstract":"BACKGROUNDInhibitor of MyoD family A (I-mfa) is a cytosolic protein. Its function in kidney is unknown. The aim of the present study was to examine the regulatory role of I-mfa on glomerular filtration rate (GFR).METHODSGFR was measured by transdermal measurement of FITC-sinitrin clearance in conscious wild type (WT) and I-mfa knockout (KO) mice. Cell contractility was assessed in a single human or mouse mesangial cell. Single cell RNA sequence (scRNA-seq), Western blot, and Ca2+ imaging were used to evaluate the effects of I-mfa on TRPCs at messenger, protein and functional levels in MCs.RESULTSIn KO mice, GFR was significantly lower than that in WT mice. In WT mice, knocking down I-mfa selectively in mesangial cells using targeted nanoparticle/siRNA delivery system significantly decreased GFR. In human mesangial cells, overexpression of I-mfa significantly blunted the Ang II-stimulated contraction, and knockdown of I-mfa significantly enhanced the contractile response. Consistently, the Ang II-induced contraction was significantly augmented in primary mesangial cells isolated from KO mice. The exaggerated response was restored by re-introducing I-mfa. Furthermore, scRNA-seq showed an increase in trpc1 messenger and Western blot showed an increase in TRPC1 protein abundance in I-mfa KO mouse mesangial cells. TRPC1 protein abundance was decreased in HEK cells overexpressing I-mfa. Ca2+ imaging experiments showed that downregulation of I-mfa significantly enhanced Ang II-stimulated Ca2+ entry in human mesangial cells. Finally, TRPC1 inhibitor, Pico145 significantly blunted Ang II-induced mesangial cell contraction.CONCLUSIONSI-mfa positively regulated GFR by decreasing mesangial cell contractile function through inhibition of TRPC1-mediated Ca2+ signaling.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"12 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmembrane Serine Protease 2 and Proteolytic Activation of the Epithelial Sodium Channel in Mouse Kidney.","authors":"Florian Sure,Sara Afonso,Daniel Essigke,Paul Schmidt,M Zaher Kalo,Viatcheslav Nesterov,Alicia Kißler,Marko Bertog,Ralf Rinke,Sabine Wittmann,Katharina A E Broeker,Thomas Gramberg,Ferruh Artunc,Christoph Korbmacher,Alexandr V Ilyaskin","doi":"10.1681/asn.0000000521","DOIUrl":"https://doi.org/10.1681/asn.0000000521","url":null,"abstract":"BACKGROUNDThe renal epithelial sodium channel (ENaC) is essential for sodium balance and blood pressure control. ENaC undergoes complex proteolytic activation by not yet clearly identified tubular proteases. Here, we examined a potential role of transmembrane serine protease 2 (TMPRSS2).METHODSMurine ENaC and TMPRSS2 were (co-)expressed in Xenopus laevis oocytes. ENaC cleavage and function were studied in TMPRSS2-deficient murine cortical collecting duct (mCCDcl1) cells and TMPRSS2-knockout (Tmprss2-/-) mice. Short-circuit currents (ISC) were measured to assess ENaC-mediated transepithelial sodium transport of mCCDcl1 cells. The mCCDcl1 cell transcriptome was studied using RNA sequencing. The effect of low-sodium diet with or without high potassium were compared in Tmprss2-/- and wildtype mice using metabolic cages. ENaC-mediated whole-cell currents were recorded from microdissected tubules of Tmprss2-/- and wildtype mice.RESULTSIn oocytes, co-expression of murine TMPRSS2 and ENaC resulted in fully cleaved γ-ENaC and ∼2-fold stimulation of ENaC currents. High baseline expression of TMPRSS2 was detected in mCCDcl1 cells without a stimulatory effect of aldosterone on its function or transcription. TMPRSS2 knockout in mCCDcl1 cells compromised γ-ENaC cleavage and reduced baseline and aldosterone-stimulated ISC which could be rescued by chymotrypsin. A compensatory transcriptional upregulation of other proteases was not observed. Tmprss2-/- mice kept on standard diet exhibited no apparent phenotype, but renal γ-ENaC cleavage was altered. In response to a low-salt diet, particularly with high potassium intake, Tmprss2-/- mice increased plasma aldosterone significantly more than wildtype mice to achieve a similar reduction of renal sodium excretion. Importantly, the stimulatory effect of trypsin on renal tubular ENaC currents was much more pronounced in Tmprss2-/- mice than that in wildtype mice. This indicated the presence of incompletely cleaved and less active channels at the cell surface of TMPRSS2-deficient tubular epithelial cells.CONCLUSIONSTMPRSS2 contributes to proteolytic ENaC activation in mouse kidney in vivo.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"40 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}