Journal of The American Society of Nephrology最新文献

{"title":"Authors' Reply: Unlocking the Potential of SC0062: A New Horizon in IgA Nephropathy Treatment?","authors":"Jianghua Chen, Hiddo J L Heerspink","doi":"10.1681/ASN.0000000657","DOIUrl":"10.1681/ASN.0000000657","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"746"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515886","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":"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":"10.1681/ASN.0000000551","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"541-543"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975230/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increasing the Removal of Large Solutes by Kidney Replacement Therapy.","authors":"Timothy W Meyer","doi":"10.1681/ASN.0000000651","DOIUrl":"10.1681/ASN.0000000651","url":null,"abstract":"<p><p>Solutes that accumulate when the kidneys fail range in size from approximately 40 to 40,000 Da. Their dialytic clearance tends to decrease as their size increases. Disproportionate accumulation of large solutes has therefore long been considered a potential contributor to residual illness in patients on dialysis. Early efforts focused on the removal of middle molecules with mass from 300 to 2000 Da. The identification of amyloidosis caused by ß2 microglobulin ( ß2 M) with mass 12,000 Da shifted the focus to low-molecular weight proteins. High-flux dialysis and hemodiafiltration increase the clearance of these larger solutes. However, nonkidney clearance and solute compartmentalization limit the extent to which their plasma levels can be lowered by increasing their clearance during treatments of standard duration. Clinical benefits of high-volume hemodiafiltration thus cannot readily be accounted for by a reduction in the levels of known large solutes. The accumulation of peptides in the original middle molecular range and the clearance of larger solutes by peritoneal dialysis have been largely neglected. There is new interest in increasing the clearance of solutes even larger than ß2 M by extended dialysis. Ongoing clinical trials will extend our knowledge of the effects of extended dialysis and hemodiafiltration. In the future, we might more effectively reduce plasma large-solute levels by manipulating their nonkidney clearance, which is now poorly understood. ß2 M is the only large solute whose accumulation in kidney failure has been shown to have specific ill effects. Identification of the ill effects of other large solutes might prompt the development of more targeted therapies.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"734-743"},"PeriodicalIF":10.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review and Meta-Analysis of Machine Learning Models for Acute Kidney Injury Risk Classification.","authors":"Augusto Cama-Olivares, Chloe Braun, Tomonori Takeuchi, Emma C O'Hagan, Kathryn A Kaiser, Lama Ghazi, Jin Chen, Lui G Forni, Sandra L Kane-Gill, Marlies Ostermann, Benjamin Shickel, Jacob Ninan, Javier A Neyra","doi":"10.1681/ASN.0000000702","DOIUrl":"https://doi.org/10.1681/ASN.0000000702","url":null,"abstract":"<p><strong>Background: </strong>Artificial Intelligence (AI) through machine learning (ML) models appears to provide accurate and precise acute kidney injury (AKI) risk classification in some clinical settings, but their performance and implementation in real-world settings has not been established.</p><p><strong>Methods: </strong>PubMed, EMBASE, Web of Science, and Scopus were searched until August 2023. Articles reporting on externally validated models for prediction of AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric patients were searched using text words related to AKI, AI, and ML. Two independent reviewers screened article titles, abstracts, and full texts. Areas under the receiver operating characteristic curves (AUCs) were used to compare model discrimination and pooled using a random-effects model.</p><p><strong>Results: </strong>Of the 4816 articles initially identified and screened, 95 were included representing 3.8 million admissions. The KDIGO-AKI criteria were the most frequently used to define AKI (72%). We identified 302 models, with the most common being logistic regression (37%), neural networks (10%), random forest (9%), and XGBoost (9%). The most frequently reported predictors of hospitalized incident AKI were age, sex, diabetes, serum creatinine, and hemoglobin. The pooled AUCs for AKI onset were 0.82 (95% CI, 0.80-0.84) and 0.78 (95% CI, 0.76-0.80) for internal and external validation, respectively. Pooled AUCs across multiple clinical settings, AKI severities, and post-AKI complications ranged from 0.78 to 0.87 for internal validation and 0.73 to 0.84 for external validation. Although data were limited, results in the pediatric population aligned with those observed in adults. Between-study heterogeneity was high for all outcomes (I2 >90%), and most studies presented high-risk of bias (86%) according to the Prediction model Risk Of Bias ASsessment Tool.</p><p><strong>Conclusions: </strong>Most externally validated models performed well in predicting AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric populations. However, heterogeneity in clinical settings, study populations, and predictors limits their generalizability and implementation at the bedside.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735996","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":"Progression of Kidney Fibrosis after Sepsis: The Underestimated Role of Resident Macrophages and Recruited Monocytes.","authors":"Charles de Roquetaillade, Manon Durand, Victor Beaucoté, Jérémie Guillemin, Christos Evangelos Chadjichristos, Antoine Roquilly, Benjamin Glenn Chousterman","doi":"10.1681/ASN.0000000712","DOIUrl":"https://doi.org/10.1681/ASN.0000000712","url":null,"abstract":"<p><strong>Abstract: </strong>Sepsis is a life-threatening condition affecting each year an estimated 49 million people and causing 11 million deaths. Short-term mortality of sepsis was substantially reduced during the past decades and is still improving. Besides its short-term lethality, awareness regarding long-term consequences of sepsis is rising. Among all organs affected during sepsis, the kidney is the most vulnerable. Up to 40% of patients suffering from sepsis develop acute kidney injury (AKI), and sepsis is the leading cause of AKI among critically ills. Half of patients will recover from AKI during their stay; however, several studies have pointed out that those patients were at increased risk for the development of subsequent chronic kidney disease (CKD). In patients suffering from transient AKI, a second injury was found to hasten renal fibrogenesis. Taken together those findings challenge the concept of ad integrum recovery and strongly suggest maladaptive repair AKI, together with profound and durable alterations at intra-organ level. Factors driving AKI to CKD after sepsis are poorly understood and could be of multiple origins. Kidney macrophages have pleiotropic roles in health and disease. Following sepsis, a proportion of kidney macrophages undergoes pyroptosis in an \"altruist\" maneuver to recruit inflammatory cells. Empty niches are later colonized by circulating monocyte arising from bone marrow in a process called emergency myelopoiesis but also by expansion of resident cells. The role of monocytes and macrophages in the acute phase of sepsis is well described, however, their role in the resolution of inflammation is just beginning to be understood. In the present review, we will discuss the fate of kidney resident macrophages and recruited monocytes in septic AKI. We will review the evidence linking changes in the immune landscape and maladaptive repair after sepsis. Finally, we will consider how targeting macrophage recruitment and polarization might influence sepsis long-term consequences.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736070","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 Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.","authors":"Juan Miguel Téllez Garcia, Thei Steenvoorden, Frederike Bemelman, Marc Hilhorst, Alessandra Tammaro, Liffert Vogt","doi":"10.1681/ASN.0000000711","DOIUrl":"https://doi.org/10.1681/ASN.0000000711","url":null,"abstract":"<p><strong>Abstract: </strong>Extracellular purines play a critical role in maintaining a balanced inflammatory response, but may also trigger disproportionate inflammation in various kidney pathologies. Extracellular ATP is the most well-characterized inflammatory purine, that serves as a potent extracellular DAMP (i.e., danger-associated molecular pattern). It signals through the P2 purinoreceptors, during both acute and chronic kidney damage. The purinoreceptor P2X7 (P2X7R) has been extensively studied in kidney disease due to its potent ability to enhance inflammation by activating the NLRP3 inflammasome in both immune and parenchymal tubular cells and potential role in immunometabolic reprogramming. We will explore how, following a primary insult to the kidney, disturbance of purinergic balance characterized by extracellular ATP-mediated P2X7R activation exacerbates acute kidney injury. Secondly, we will describe how persistent purinergic disbalance promotes a P2X7R-mediated protracted inflammatory reaction leading to the progression of chronic kidney disease of different etiologies. Lastly, we will also highlight the relevant and emerging role of P2X7R signaling in both antigen presenting cells and adaptive immune cells to modulate cellular and humoral immune responses in kidney transplantation and hypertension. This review underscores that ATP-P2X7R axis is a key driver of pathological purinergic signaling, representing a largely unexplored but highly promising clinical target against a wide spectrum of kidney diseases.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736000","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":"Effects of Prothrombin on Podocytopathy and Proteinuria in Glomerular Disease.","authors":"Amanda P Waller, Katelyn J Wolfgang, Iva Pruner, Zachary S Stevenson, Eman Abdelghani, Kaushik Muralidharan, Tasha K Wilkie, Angela R Blissett, Edward P Calomeni, Tatyana A Vetter, Sergey V Brodsky, William E Smoyer, Marvin T Nieman, Bryce A Kerlin","doi":"10.1681/ASN.0000000676","DOIUrl":"https://doi.org/10.1681/ASN.0000000676","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) is a leading cause of death, its progression is driven by glomerular podocyte injury and loss, manifesting as proteinuria. Proteinuria includes loss of coagulation zymogens, cofactors, and inhibitors resulting in a hypercoagulable state characterized by enhanced thrombin generation. Both CKD and proteinuria significantly increase the risk of thromboembolic disease. Meanwhile, anticoagulant medications (which antagonize thrombin and thereby prevent thromboembolism) have been shown to reduce proteinuria in rats and thrombin has been shown to injure cultured human and rat podocytes. We thus aimed to directly determine the influence of circulating prothrombin, the zymogen precursor of thrombin, on glomerular pathobiology. We hypothesized that (pro)thrombin drives podocytopathy, podocytopenia, and proteinuria.</p><p><strong>Methods: </strong>Glomerular proteinuria was induced with puromycin aminonucleoside in rats. Prothrombin was either knocked down using an antisense oligonucleotide targeting prothrombin mRNA or elevated by serial intravenous prothrombin protein infusions, previously established methods to model hypo- and hyper-prothrombinemia, respectively. After 10 days plasma prothrombin levels were determined, kidneys were examined for (pro)thrombin co-localization to podocytes, histology, and electron microscopy. Podocytopathy, podocytopenia, proteinuria, and plasma albumin were measured.</p><p><strong>Results: </strong>Antisense oligonucleotide-mediated prothrombin knockdown significantly reduced prothrombin colocalization to podocytes, tubular injury, podocyte foot process effacement, podocytopathy, and proteinuria along with improved plasma albumin in the puromycin aminonucleoside glomerular disease model. In contrast, elevated prothrombin levels significantly increased podocytopathy and proteinuria. Podocytopenia was significantly improved in hypo-prothrombinemic vs. hyper-prothrombinemic rats.</p><p><strong>Conclusions: </strong>Thrombin generation is enhanced by glomerular proteinuria and thrombin injures conditionally immortalized podocytes in vitro. In the present study, prothrombin knockdown ameliorated in vivo podocyte injury and improved podocyte function in the rat puromycin aminonucleoside-induced glomerular disease model whereas hyper-prothrombinemia exacerbated podocyte injury and diminished podocyte function.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736066","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 Drug-Screening Platform for Podocytopathies in Drosophila Nephrocytes.","authors":"Dominik Spitz, Jost Wiggering, Chiranth Prakash, Maximilian H Ulbrich, Ronen Schneider, Tobias Hermle","doi":"10.1681/ASN.0000000677","DOIUrl":"https://doi.org/10.1681/ASN.0000000677","url":null,"abstract":"<p><strong>Background: </strong>The complex cellular architecture of the glomerular filtration barrier is not recapitulated in vitro, representing a major obstacle for drug screening. This contributes significantly to a therapeutic gap for the heterogeneous diseases affecting the podocyte. Phenotypic drug screening using whole organisms is inherently slow but can reveal entirely unexpected therapies that are unattainable by conventional screening. The Drosophila nephrocyte features a molecularly conserved filtration barrier, suitable for whole-animal screening in podocytopathies.</p><p><strong>Methods: </strong>We generated transgenic Drosophila expressing a secretable variant of Green Fluorescent Protein as a genetically encoded tracer for rapid analysis of nephrocyte function. Animals were exposed to drugs in liquid food before recording nephrocyte fluorescence intensity. The slit diaphragm architecture was investigated using immunofluorescence and subsequent automated quantification.</p><p><strong>Results: </strong>The genetically encoded tracer, combined with fast detection through enhanced widefield fluorescence microscopy, provided a faster but reliable screening assay for nephrocyte function compared with the established approach using FITC-albumin ex vivo. Rac1 is a key regulator of the actin cytoskeleton, involved in maintaining podocyte structure and function. In nephrocytes, overexpression of Rac1 resulted in mislocalization of slit diaphragm proteins and deeper membrane invaginations. Since nephrocyte function was further decreased as detected by the novel assay, we used this screening background relevant to podocyte biology for a pilot screen of 100 drugs. We identified significant improvement of nephrocyte function for zacopride, a respective agonist or antagonist of serotonin receptors, which restored the slit diaphragm architecture despite overexpression of Rac1. The mechanism of action of zacopride appeared independent from the orthologs of the mammalian target proteins or direct Rac1 inhibition, suggesting a pleiotropic target. This hit from the pilot screen illustrates the potential of phenotypic drug screening to reveal unexpected therapeutic options.</p><p><strong>Conclusions: </strong>We present a proof-of-concept for whole-animal drug screening using podocyte-like Drosophila nephrocytes.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719861","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":"Complement Inhibition Therapy in IgA Nephropathy: Total or Selective Inhibition?","authors":"Zhiyong Zhu, Chengcai Zhang, Hongyun Wang, Baozhen Li","doi":"10.1681/ASN.0000000673","DOIUrl":"https://doi.org/10.1681/ASN.0000000673","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730679","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: Complement Inhibition Therapy in IgA Nephropathy: Total or Selective Inhibition?","authors":"Jonathan Barratt, Katherine Garlo, Andreas Kateifides, Richard Lafayette","doi":"10.1681/ASN.0000000674","DOIUrl":"https://doi.org/10.1681/ASN.0000000674","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730615","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}