Journal of The American Society of Nephrology最新文献

{"title":"Pathogenesis of Organ Damage in Fabry Disease: The AGALopathy Pathogenetic Pathway.","authors":"Paula Rozenfeld, Sandro Feriozzi","doi":"10.1681/ASN.0000000625","DOIUrl":"https://doi.org/10.1681/ASN.0000000625","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071042","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":"Genome-Wide Association Study of Plasma Sodium Concentrations with and without Exposure to Thiazide Diuretics.","authors":"Niklas Worm Andersson, Xiaoping Wu, Frank Geller, Jan Wohlfahrt, Mads Melbye, Anders Hviid, Michael Schwinn, Christina Mikkelsen, Joseph Dowsett, Mie Topholm Bruun, Bitten Aagaard, Henrik Ullum, Christian Erikstrup, Daniel Fannar Gudbjartsson, Kári Stefánsson, Jonas Ghouse, Ole Birger Pedersen, Erik Sørensen, Sisse Rye Ostrowski, Henning Bundgaard, Marie Lund, Bjarke Feenstra","doi":"10.1681/ASN.0000000622","DOIUrl":"https://doi.org/10.1681/ASN.0000000622","url":null,"abstract":"<p><strong>Background: </strong>Abnormal plasma sodium concentration represents an imbalance of total body water relative to electrolyte content. Hyponatremia is a common and potentially severe adverse event, and thiazide diuretics constitute a leading cause of drug-induced hyponatremia.</p><p><strong>Methods: </strong>We conducted genome-wide association study analyses of plasma sodium concentration, thiazide-induced decrease in sodium concentration, and thiazide-induced hyponatremia in a total of 188,464 individuals of European ancestry . Additionally, we tested for gene-environment interaction between a polygenic score developed for plasma sodium concentration and thiazide exposure on sodium concentration and hyponatremia risk.</p><p><strong>Results: </strong>Meta-analysis yielded 31 independent associated signals at P<5×10-8 with plasma sodium concentrations. Subsequent tissue specificity analysis showed a significantly increased expression of sodium-associated genes in pituitary tissue (P=4.5×10-5). No genome-wide significant loci were found for thiazide-induced sodium concentration decrease or thiazide-induced hyponatremia. A polygenic score for plasma sodium concentration was associated with 0.43 (95% confidence interval (CI) = 0.39-0.46) mmol/L lower plasma sodium per standard deviation lower, and thiazide use was associated with 0.80 (95% CI=0.72-0.88) mmol/L lower plasma sodium, but we observed no gene-environment interaction effect (P=0.71).</p><p><strong>Conclusions: </strong>These results underline the role of genetic variation in regulating plasma sodium concentration and highlight the importance of pathways involving the pituitary gland while finding no evidence of genetic predisposition for the plasma sodium-lowering effect of thiazides.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070972","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":"Post-transplant Thrombotic Microangiopathy.","authors":"Anuja Java, Matthew A Sparks, David Kavanagh","doi":"10.1681/ASN.0000000645","DOIUrl":"10.1681/ASN.0000000645","url":null,"abstract":"<p><p>Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation that significantly affects graft and patient survival, occurring in 0.8%-15% of transplant recipients. TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury due to endothelial damage and microthrombi formation in small vessels. However, clinical features can range from a renal-limited form, diagnosed only on a kidney biopsy, to full-blown systemic manifestations, which include neurologic, gastrointestinal, and cardiovascular injury. TMA can arise because of genetic or acquired defects such as in complement-mediated TMA or can occur in the context of other conditions like infections, autoimmune diseases, or immunosuppressive drugs, where complement activation may also play a role. Recurrent TMA after kidney transplant is almost always complement-mediated, although complement overactivation may also play a role in de novo post-transplant TMAs associated with ischemia-reperfusion injury, immunosuppressive drugs, antibody-mediated rejection, viral infections, and relapse of autoimmune diseases, such as antiphospholipid antibody syndrome. Differentiating between a complement-mediated process and one triggered by other factors is often challenging but critical to minimize allograft damage because the former is nonresponsive to supportive therapy, needs long-term anticomplement therapy, and has a high risk of recurrence. Given the central role of complement and effect of genetic defects on the risk of recurrence in many forms of post-transplant TMA, genetic testing for complement disorders is key for proper diagnosis and management. Given that complement activation may also play a role in a subset of TMAs associated with other conditions, prompt recognition and timely initiation of anticomplement therapy is equally important. In addition, TMA associated with noncomplement genes, often part of a broader syndromic process with distinct clinical features, has also been described. Early identification and treatment are essential to prevent graft failure and other severe complications. This review explores the pathophysiologic mechanisms underlying various post-transplant TMAs.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071046","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: Competing Risk Models Should Be Considered When Estimating Kidney Allograft Failure.","authors":"Agathe Truchot, Marc Raynaud, Alexandre Loupy","doi":"10.1681/ASN.0000000630","DOIUrl":"10.1681/ASN.0000000630","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070968","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":"Anti-slit Antibodies against Podocin and Kirrel1 in Pediatric and Adult Podocytopathies.","authors":"Valentina Raglianti,Maria Lucia Angelotti,Letizia De Chiara,Marco Allinovi,Luigi Cirillo,Anna Manonelles Montero,Josep Maria Cruzado,Maria Elena Melica,Giulia Antonelli,Carolina Conte,Anna Julie Peired,Laura Lasagni,Bärbel Lange-Sperandio,Hans-Joachim Anders,Francesca Becherucci,Elena Lazzeri,Benedetta Mazzinghi,Paola Romagnani","doi":"10.1681/asn.0000000642","DOIUrl":"https://doi.org/10.1681/asn.0000000642","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062028","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":"Autoantibodies in the Pathogenesis of Podocytopathies.","authors":"Lukas Blume,Catherine Meyer-Schwesinger","doi":"10.1681/asn.0000000624","DOIUrl":"https://doi.org/10.1681/asn.0000000624","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"121 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062039","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":"Interplay between Skeletal Muscle Catabolism and Remodeling of Arteriovenous Fistula via YAP1 Signaling.","authors":"Yongdong Wu,Tae Hoon Lee,Owen H Cheng,Eric Peden,Qingtian Li,Jun Wang,Fengzhang Huang,Marites P Melancon,David Sheikh-Hamad,Tao Wang,Luan Truong,William Mitch,Ming Liang,Jizhong Cheng","doi":"10.1681/asn.0000000605","DOIUrl":"https://doi.org/10.1681/asn.0000000605","url":null,"abstract":"BACKGROUNDArteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. This study aims to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure.METHODSSkeletal muscle metabolism and AV fistula maturation were evaluated in mice with chronic kidney disease (CKD). The roles of myostatin and YAP1 in regulating the transdifferentiation of adventitial mesenchymal stem cells (mesenchymal stem cells) and intima hyperplasia in AV fistula were investigated. Nanoparticles carrying a YAP1 inhibitor, verteporfin, with light irradiation-controlled release were synthesized and applied to AV fistula.RESULTSIncreased trichrome signals and stenosis were observed in AV fistulas from mice treated with myostatin and from mice with CKD. In contrast, blocking myostatin function with an anti-myostatin peptibody not only improved body weight and muscle size in CKD mice but also decreased neointima formation in AV fistulas. In cultured mesenchymal stem cells, myostatin induced YAP1 expression, promoting the differentiation of mesenchymal stem cells into myofibroblasts and inducing extracellular matrix deposition. Red light irradiation-controlled release of verteporfin from nanoparticles blocked YAP1 activation and alleviated myostatin-induced mesenchymal stem cell activation. Periadventitial application and red-light irradiation of nanoparticles carrying verteporfin significantly suppressed stiffening and neointima formation in AV fistula.CONCLUSIONSCKD induced muscle wasting leading to increased production of myostatin, which stimulated mesenchymal stem cell activation and vascular fibrosis linked to AV fistula stenosis. YAP1 signaling was activated in these processes. Red-light irradiation-controlled release of verteporfin offered a feasible approach for local vascular drug intervention to improve AV fistula maturation.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"121 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062057","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":"KidneyintelX.dkd: An Innovation in Precision Medicine for Diabetic Kidney Disease.","authors":"Steven G Coca,Girish N Nadkarni","doi":"10.1681/asn.0000000644","DOIUrl":"https://doi.org/10.1681/asn.0000000644","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"54 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062084","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":"Mechanotransduction and the Integrity of the Slit Diaphragm.","authors":"Rose Z Hill","doi":"10.1681/asn.0000000618","DOIUrl":"https://doi.org/10.1681/asn.0000000618","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"22 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057185","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":"Integrin Trafficking, Fibronectin Architecture, and Glomerular Injury upon AdipoR1 Depletion.","authors":"Sonja Lindfors,Constanze Schmotz,Dominik Lewandowski,Annika Hau,Leena Saikko,Eero Lehtonen,Ville Majaniemi,Minna Karhe,Jette-Britt Naams,Harry Nisen,Jukka Tienari,Moin A Saleem,Katharina Pfeil,Heiko Bugger,Kirsi H Pietiläinen,Tuomas Mirtti,Krzysztof Palczewski,Sanna Lehtonen","doi":"10.1681/asn.0000000611","DOIUrl":"https://doi.org/10.1681/asn.0000000611","url":null,"abstract":"BACKGROUNDDeficiency of adiponectin and its downstream signaling may contribute to the pathogenesis of kidney injury in type 2 diabetes. Adiponectin activates intracellular signaling via adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2), but the role of AdipoR-mediated signaling in glomerular injury in type 2 diabetes remains unknown.METHODSThe expression of AdipoR1 in the kidneys of people with type 2 diabetes and the expression of podocyte proteins or injury markers in the kidneys of AdipoR1-knockout (AdipoR1-KO) mice and immortalized AdipoR1-deficient human podocytes were investigated by immunohistochemistry and immunoblotting. The functional role of AdipoR1 was studied in AdipoR1-deficient podocytes by performing assays for apoptosis, cytokine secretion, mechanical stress, adhesion, and endocytic trafficking.RESULTSGlomerular AdipoR1 expression was lower in type 2 diabetes and associated kidney disease, correlating with higher BMI and podocyte loss. Male AdipoR1-KO mice showed typical signs of early diabetic kidney disease, including albuminuria, glomerular structural abnormalities, and lower expression of central podocyte proteins; females were less affected. Podocyte apoptosis increased in female and male AdipoR1-KO mice and excessive podocyte loss, potentially due to detachment, was detected in males. AdipoR1 deficiency impaired the YAP-mediated mechanoresponse and induced accumulation of the extracellular matrix (ECM) protein fibronectin in the glomeruli in vivo, and podocytes in vitro. Functionally, AdipoR1 deficiency impaired endocytosis of the ECM receptor active integrin β1, disturbed focal adhesion turnover, and remodulated podocyte-derived ECM, thereby reducing podocyte adhesion.CONCLUSIONSAdipoR1 deficiency in mice resulted in the development of kidney injury predominantly in males. Mechanistically, AdipoR1 loss in podocytes impaired endocytosis of active integrin β1, which plausibly compromised focal adhesion dynamics, disturbed fibronectin matrix turnover, and hindered podocyte adhesion.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"60 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056900","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}