Journal of The American Society of Nephrology最新文献

{"title":"Piezo, Nephrocyte Function, and Slit Diaphragm Maintenance in Drosophila.","authors":"Yunpo Zhao,Jianli Duan,Iden D Han,Joyce van de Leemput,Patricio E Ray,Zhe Han","doi":"10.1681/asn.0000000529","DOIUrl":"https://doi.org/10.1681/asn.0000000529","url":null,"abstract":"BACKGROUNDThe Piezo gene encodes a highly conserved cell membrane protein responsible for sensing pressure. The glomerular kidney and the slit diaphragm filtration structure depend on pressure for filtration. However, how Piezo is involved in kidney function and in maintaining the slit diaphragm filtration structure is not clear.METHODSWe used Drosophila pericardial nephrocytes, filtration kidney cells with striking structural and functional similarities to human podocytes, in a loss-of-function model (mutant and knockdown) to study the roles of Piezo in nephrocyte filtration and function.RESULTSPiezo is highly expressed at the invaginated membranes (lacuna channels) of nephrocytes. A Piezo loss-of-function mutant showed significant nephrocyte functional decline. Nephrocyte-specific silencing of Piezo showed disruption of the slit diaphragm filtration structure and significant functional defects. Electron microscopy showed that silencing Piezo in nephrocytes leads to reduced slit diaphragm density and abnormal shape of lacuna channels. Moreover, the Piezo-deficient nephrocytes showed internalized slit diaphragm component proteins, reduced autophagy, increased ER stress, and reduced calcium influx.CONCLUSIONSTogether, our findings suggest that Piezo plays an important role in the calcium homeostasis of nephrocytes and is required for maintaining nephrocyte function and the slit diaphragm filtration structure.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"8 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486319","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":"Piezo, Nephrocyte Function, and Slit Diaphragm Maintenance in Drosophila.","authors":"Yunpo Zhao, Jianli Duan, Iden D Han, Joyce van de Leemput, Patricio E Ray, Zhe Han","doi":"10.1681/ASN.0000000529","DOIUrl":"10.1681/ASN.0000000529","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468648","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":"Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure.","authors":"Agathe Truchot,Marc Raynaud,Ilkka Helanterä,Olivier Aubert,Nassim Kamar,Gillian Divard,Brad Astor,Christophe Legendre,Alexandre Hertig,Matthias Buchler,Marta Crespo,Enver Akalin,Gervasio Soler Pujol,Maria Cristina Ribeiro de Castro,Arthur J Matas,Camilo Ulloa,Stanley C Jordan,Edmund Huang,Ivana Juric,Nikolina Basic-Jukic,Maarten Coemans,Maarten Naesens,John J Friedewald,Helio Tedesco Silva,Carmen Lefaucheur,Dorry L Segev,Gary S Collins,Alexandre Loupy","doi":"10.1681/asn.0000000517","DOIUrl":"https://doi.org/10.1681/asn.0000000517","url":null,"abstract":"BACKGROUNDPrognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes.METHODSWe included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance.RESULTSAmong 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach.CONCLUSIONSCompeting and noncompeting risk models performed similarly in predicting long-term kidney graft failure.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"232 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448054","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":"Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies.","authors":"Philipp Gauckler, Anna Matyjek, Seleni Kapsia, Smaragdi Marinaki, Luis F Quintana, Montserrat M Diaz, Catherine King, Siân Griffin, Raja Ramachandran, Balazs Odler, Kathrin Eller, Ayşe Serra Artan, Safak Mirioglu, Martin Busch, Maxi Schaepe, Kultigin Turkmen, Chee Kay Cheung, Ruth J Pepper, Gema Fernandez Juarez, Julio Pascual, Pilar Auñón, Clara García-Carro, Antolina Rodriguez, Federico Alberici, Leonella Luzardo, Natalia Chebotareva, Ulf Schönermarck, Loreto Fernández, Jai Radhakrishnan, Karina Guaman, Yonatan Peleg, Léa Hoisnard, Vincent Audard, Marios Papasotiriou, Nina Krnanska, Vladimir Tesar, Zdenka Hruskova, Annette Bruchfeld, Maria Stangou, Georgios Lioulios, Stanislas Faguer, David Ribes, Sofiane Salhi, Martin Windpessl, Krešimir Galešić, Matija Crnogorac, Nikola Zagorec, Gert Mayer, Andreas Kronbichler","doi":"10.1681/ASN.0000000520","DOIUrl":"10.1681/ASN.0000000520","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468646","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":"Toward a Restrictive Use of Plasma Exchanges in Thrombotic Microangiopathies.","authors":"Marie Frimat,Nora Schwotzer,François Provôt,Fadi Fakhouri","doi":"10.1681/asn.0000000555","DOIUrl":"https://doi.org/10.1681/asn.0000000555","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448051","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":"Authors' Reply: The Potential Outcome-Modification Influences Introduced by ESKD Life Plan on eGFR Slopes.","authors":"Abdel-Hay Tabcheh,Julie Boucquemont,Roberto Pecoits-Filho,Natalia Alencar De Pinho,","doi":"10.1681/asn.0000000523","DOIUrl":"https://doi.org/10.1681/asn.0000000523","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"19 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448053","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 Potential Outcome-Modification Influences Introduced by ESKD Life Plan on eGFR Slopes.","authors":"Kuo-Chin Hung,Chia-Ter Chao","doi":"10.1681/asn.0000000522","DOIUrl":"https://doi.org/10.1681/asn.0000000522","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"65 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448050","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":"A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases.","authors":"Goran Stanajic-Petrovic, Mathilde Keck, Peggy Barbe, Apolline Urman, Evelyne Correia, Pierre Isnard, Jean-Paul Duong Van Huyen, Khawla Chmeis, Sékou Siramakan Diarra, Stefano Palea, Frederic Theodoro, Anvi-Laëtitia Nguyen, Florence Castelli, Alain Pruvost, Wenchao Zhao, Christiane Mendre, Bernard Mouillac, Frank Bienaimé, Philippe Robin, Pascal Kessler, Catherine Llorens-Cortes, Denis Servent, Hervé Nozach, Bernard Maillère, Dong Guo, Charles Truillet, Nicolas Gilles","doi":"10.1681/ASN.0000000505","DOIUrl":"10.1681/ASN.0000000505","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468647","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":"Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies.","authors":"Philipp Gauckler,Anna Matyjek,Seleni Kapsia,Smaragdi Marinaki,Luis F Quintana,Montserrat M Diaz,Catherine King,Siân Griffin,Raja Ramachandran,Balazs Odler,Kathrin Eller,Ayşe Serra Artan,Safak Mirioglu,Martin Busch,Maxi Schaepe,Kultigin Turkmen,Chee Kay Cheung,Ruth J Pepper,Gema Fernandez Juarez,Julio Pascual,Pilar Auñón,Clara García-Carro,Antolina Rodriguez,Federico Alberici,Leonella Luzardo,Natalia Chebotareva,Ulf Schönermarck,Loreto Fernández,Jai Radhakrishnan,Karina Guaman,Yonatan Peleg,Léa Hoisnard,Vincent Audard,Marios Papasotiriou,Nina Krnanska,Vladimir Tesar,Zdenka Hruskova,Annette Bruchfeld,Maria Stangou,Georgios Lioulios,Stanislas Faguer,David Ribes,Sofiane Salhi,Martin Windpessl,Krešimir Galešić,Matija Crnogorac,Nikola Zagorec,Gert Mayer,Andreas Kronbichler,","doi":"10.1681/asn.0000000520","DOIUrl":"https://doi.org/10.1681/asn.0000000520","url":null,"abstract":"BACKGROUNDLong-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown.METHODSA retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months.RESULTS183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching -11 (95% CI: -18 to -8) mL/min/1.73m2 .CONCLUSIONSRituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab further associated with long-term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486322","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":"MQ232, A Snake Toxin Derivative for Treatment of Hyponatremia and Polycystic Kidney Diseases.","authors":"Goran Stanajic-Petrovic,Mathilde Keck,Peggy Barbe,Apolline Urman,Evelyne Correia,Pierre Isnard,Jean-Paul Duong Van Huyen,Khawla Chmeis,Sékou Siramakan Diarra,Stefano Palea,Frederic Theodoro,Anvi-Laëtitia Nguyen,Florence Castelli,Alain Pruvost,Wenchao Zhao,Christiane Mendre,Bernard Mouillac,Frank Bienaimé,Philippe Robin,Pascal Kessler,Catherine Llorens-Cortes,Denis Servent,Hervé Nozach,Bernard Maillère,Dong Guo,Charles Truillet,Nicolas Gilles","doi":"10.1681/asn.0000000505","DOIUrl":"https://doi.org/10.1681/asn.0000000505","url":null,"abstract":"BACKGROUNDVaptans were developed at the end of the previous century as V2R antagonists. Tolvaptan is the most prescribed vaptan for hyponatremia and the autosomal polycystic kidney disease (ADPKD). However, its use is not as widespread as it should be due to price issues, a narrow therapeutic window and some side effects. With the aim of discovering new efficient and safer V2R antagonists, we screened animal venoms and identified several interesting peptide toxins. Among them, MQ1 displayed such unique biological properties in that regard that it was the starting point for the development of a potential drug candidate.METHODSHuman T-cell assays and bioinformatics was used to mitigate MQ1 immunogenicity risk. The MQ232 biodistribution in mice was done by positron emission tomography (PET). Pharmacodynamics, pharmacokinetics, acute and chronic toxicity tests were performed on control rats. A rat experimental model of dDAVP-induced hyponatremia, an ex vivo mice model of renal cysts and a mice orthologous model of ADPKD were used to validate MQ232 efficacy in these pathologies.RESULTSThree mutations were introduced in MQ1 to mitigate its immunogenicity risk. A fourth gain-of-function mutation was added to generate MQ232. MQ232's safety was demonstrated by a first toxic dose as high as 3,000 nmol/kg and a strong kidney organ selectivity by PET imaging, while showing almost no interaction with the liver. MQ232's efficacy was first demonstrated with an effective dose of 3 nmol/kg in a hyponatremic model, and then in polycystic kidney models on which MQ232 significantly reduced cyst growth.CONCLUSIONSWe demonstrated, employing diverse translational techniques and minimizing animal use, MQ232's safety and efficacy in several rodent models of hyponatremia and ADPKD.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486337","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}