Journal of The American Society of Nephrology最新文献

{"title":"ASN Kidney Health Guidance on the Cardiovascular-Kidney-Metabolic Syndrome.","authors":"Nisha Bansal, Petter Bjornstad, Adam P Bress, Tara I Chang, Xingxing Cheng, Michelle M Estrella, Alan S Go, Amy K Mottl, Sankar D Navaneethan, Brendon L Neuen, Brian S Rifkin, Kim Zuber, Alexander R Chang","doi":"10.1681/ASN.0000001231","DOIUrl":"10.1681/ASN.0000001231","url":null,"abstract":"<p><strong>Key points: </strong>The cardiovascular-kidney-metabolic (CKM) syndrome framework has important implications in the care of people with kidney diseases. Cardiovascular screening is important in people with kidney diseases, but the approach may differ in this high-risk population. Multiple pharmacotherapies for CKM syndrome offer significant cardiovascular and kidney benefits.</p><p><p>Cardiovascular-kidney-metabolic (CKM) syndrome highlights the interconnected nature of cardiovascular disease, CKD, and metabolic dysfunction and underscores the need for integrated approaches to prevention and treatment. Patients with kidney diseases are at markedly elevated risk for atherosclerotic cardiovascular events, heart failure, kidney failure, and premature mortality across the spectrum of kidney disease severity. Recent advances in therapeutics, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1)-based therapies, and nonsteroidal mineralocorticoid receptor antagonists, alongside established renin-angiotensin system inhibitors and lipid-lowering therapies, have transformed the management of CKM by demonstrating both cardiovascular and kidney benefits. However, important gaps remain in applying the CKM framework to patients with kidney diseases, particularly among individuals with advanced CKD, kidney failure treated with dialysis, kidney transplant recipients, younger and older individuals, and those with nonmetabolic kidney diseases including glomerular disorders. This American Society of Nephrology Kidney Health Guidance provides practical guidance for nephrology clinicians on screening, risk stratification, and pharmacologic management across the CKM spectrum. The guidance emphasizes the importance of longitudinal assessment of estimated glomerular filtration rate and albuminuria as foundational markers of cardiovascular and kidney risk, including the role of cardiac biomarkers and imaging. Integration of cardiovascular and kidney risk prediction models, including the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations and the Kidney Failure Risk Equation (KFRE), may support early identification of high-risk patients and guide treatment intensification. The guidance also reviews evidence supporting sequential and combination approaches to CKM therapies, strategies for managing adverse effects, and special considerations for CKD subpopulations where data are more limited. Adoption of a CKM framework in nephrology practice promotes coordinated, multidisciplinary care and provides an opportunity to shift from organ-specific management toward a more holistic approach aimed at reducing cardiovascular events, slowing kidney disease progression, and improving patient-centered outcomes across the continuum of kidney disease.</p><p><strong>Podcast: </strong>This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2282-2305"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881050","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":"Gestational Ketosis Compromises Nephron Endowment and Long-Term Kidney Function in Offspring.","authors":"Athar Amleh, Yaniv Makayes, Eden Abergel, Dan Binyamin Varshavsky, Hadar Benyamini, Inbar Plaschkes, Morris Nechama, Oded Volovelsky","doi":"10.1681/ASN.0000001126","DOIUrl":"10.1681/ASN.0000001126","url":null,"abstract":"<p><strong>Key points: </strong>Maternal ketosis disrupted nephrogenesis, reduced proliferation, and suppressed Myc and cell cycle signaling. Offspring exhibited persistent kidney deficits, including reduced nephron endowment and compromised long-term kidney function. Gestational ketosis developmental risks highlighted the need for metabolic monitoring and dietary guidance during pregnancy.</p><p><strong>Background: </strong>The increasing popularity of ketogenic diets raises concerns regarding their safety during pregnancy. While mild ketosis is a common metabolic adaptation in gestation, the effect of diet-induced, supraphysiological ketosis on fetal kidney development remains unknown. We aimed to investigate the effects of maternal ketosis on offspring nephrogenesis and long-term kidney outcomes.</p><p><strong>Methods: </strong>Two complementary murine models were used: maternal exposure to a ketogenic diet or β -hydroxybutyrate supplementation throughout gestation. Offspring were evaluated at birth and during postnatal development. Kidney structure and function were assessed using nephron counts, kidney size, and serum markers of kidney function and injury. Nephron progenitor cell (NPC) dynamics were examined using RNA sequencing, gene set enrichment analysis, immunostaining, and quantitative PCR to assess proliferation and inflammation-related markers.</p><p><strong>Results: </strong>Both the ketogenic diet and β -hydroxybutyrate supplementation models induced maternal ketosis and reduced offspring nephron number. Offspring exhibited impaired kidney function, which was more pronounced in the ketogenic diet group. Transcriptomic analysis of NPCs revealed downregulation of cell cycle and Myc signaling pathways, alongside upregulation of inflammatory pathways, including TNF- α /NF-κB signaling. Immunostaining confirmed reduced NPC proliferation and c-Myc expression, alongside increased TNF- α expression. Although postnatal NPC proliferation partially recovered after reversion to a normal diet, it was insufficient to rescue the nephron endowment deficit.</p><p><strong>Conclusions: </strong>Maternal ketosis disrupted nephrogenesis by suppressing c-Myc signaling and activating inflammatory pathways in NPCs, leading to a congenital nephron deficit and compromised adult kidney function.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2132-2145"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839599","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":"Eupalinolide B Ameliorates Diabetic Kidney Disease via Inhibition of Cell Division Cycle 37-Mediated Inflammatory Pathways.","authors":"Huiying Li, Guanjun Li, Ling Huang, Tianyun Fan, Ying Zhang, Junzhe Zhang, Liwei Gu, Jianyou Wang, Li Hu, Huan Tang, Yali Song, Qingming Luo, Jigang Wang","doi":"10.1681/ASN.0000001122","DOIUrl":"10.1681/ASN.0000001122","url":null,"abstract":"<p><strong>Key points: </strong>A natural sesquiterpene lactone compound Eupalinolide B protected against diabetic kidney disease. Eupalinolide B targeted cell division cycle 37 protein and disrupted the interaction between cell division cycle 37 and heat shock protein 90. The renoprotective effects of Eupalinolide B were dependent on cell division cycle 37-mediated inflammatory pathways in diabetic kidney disease.</p><p><strong>Background: </strong>Diabetic kidney disease (DKD) is a major complication of diabetes, driven by chronic inflammation throughout its initiation and progression. Developing effective novel therapeutics is urgently needed. Eupalinolide B, a natural small compound derived from Eupatorium lindleyanum DC ., has multiple bioactive properties, notably antitumor and anti-inflammatory activities. However, the therapeutic potential of Eupalinolide B for DKD remains unclear. This study was to investigate the potential effects, direct targets, and pharmacologic mechanisms of Eupalinolide B against DKD, and discover novel therapeutic targets in the progression of DKD.</p><p><strong>Methods: </strong>The therapeutic effects of Eupalinolide B were assessed in high glucose-induced rat mesangial (HBZY-1) cells and db/db diabetic mice. Targeting and binding site engagement of Eupalinolide B was validated through activity-based protein profiling technology, pull-down assay, surface plasmon resonance analysis, and high-resolution mass spectrometry analysis. The target protein was knocked down to investigate its role in DKD-related inflammation and determine whether Eupalinolide B's renoprotective effects depend on the protein. The impact of Eupalinolide B on protein-protein interactions was examined using immunoblotting, immunohistochemistry, immunofluorescence, and coimmunoprecipitation assays.</p><p><strong>Results: </strong>Eupalinolide B was observed to ameliorate the glomerular filtration dysfunction and histopathologic damage in db/db mice and suppress NF-κB and mitogen-activated protein kinase proinflammatory pathways in both high glucose-induced HBZY-1 cells and db/db mice. In addition, we found that Eupalinolide B directly bound to cysteine 64 and 234 residues of cell division cycle 37 (CDC37), the essential cochaperone of heat shock protein 90 (HSP90). Mechanistically, by targeting CDC37, Eupalinolide B disrupted the interaction between CDC37 and HSP90, consequently blocking downstream proinflammatory signaling upon high glucose induction in HBZY-1 cells.</p><p><strong>Conclusions: </strong>Eupalinolide B was identified as a novel CDC37-targeting agent with renoprotective and anti-inflammatory effects against DKD that functions by inhibiting CDC37-HSP90 interaction.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2146-2161"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874724","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":"Dual B -Cell Maturation Antigen/CD19 Chimeric Antigen Receptor- T Therapy for AL Amyloidosis : Targeting the Clone, Saving the Kidney.","authors":"Klaudia Sobczak, Mark B Leick","doi":"10.1681/ASN.0000001223","DOIUrl":"10.1681/ASN.0000001223","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2097-2099"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794835","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":"Kidney Epithelial AKT Controls Potassium Homeostasis and Metabolic Adaptation","authors":"Masa-Ki Inoue,Yahua Zhang,Alondra Vázquez Rivera,Clinton M. Hasenour,Juan Pablo Arroyo,Fabian Bock,Alina Yu,Izumi Kaji,Mohammed Z. Ferdaus,Eric Delpire,Jamey D. Young,Ming-Zhi Zhang,Raymond C. Harris,Andrew S. Terker","doi":"10.1681/asn.0000001278","DOIUrl":"https://doi.org/10.1681/asn.0000001278","url":null,"abstract":"Background: Potassium intake is strongly associated with cardiometabolic health, yet the mechanisms linking electrolyte balance to systemic metabolism remain poorly defined. We hypothesized that renal epithelial AKT acts as a potassium-responsive signaling node that coordinates potassium homeostasis and metabolic adaptation. Methods: Inducible nephron-wide and proximal tubule-specific AKT1/AKT2 knockout mice were generated to define the role of epithelial AKT in renal potassium handling and metabolism. Physiologic, molecular, proteomic, and metabolic analyses were performed under normal and potassium-restricted dietary conditions, complemented by mechanistic studies in cultured cells. Results: Proteomic analysis revealed that dietary potassium restriction stimulated AKT-dependent pathways in the kidney, including glycolysis and de novo lipogenesis. Nephron-wide and proximal tubule-specific AKT deletion impaired adaptation to potassium deprivation, resulting in urinary potassium wasting, reduced kidney hypertrophy, diminished proximal tubule transporter expression, and hypokalemia. Mechanistically, AKT loss suppressed low-K + -induced glycolytic and lipogenic programs, reduced de novo palmitate synthesis, and promoted a renal catabolic, ketogenic phenotype characterized by increased HMGCS2 expression and ketone production. In vitro studies showed that low-potassium-induced AKT activation required mTOR activity but was independent of Rictor, whereas Sin1 and mLST8 were essential. AKT deletion also reduced expression of the proximal tubule glucose transporters SGLT1 and SGLT2, causing glycosuria. These renal adaptations were accompanied by lower fasting glucose levels, improved glucose tolerance, enhanced insulin sensitivity, and increased AKT signaling in liver and skeletal muscle. Conclusions: Renal epithelial AKT was required for adaptation to dietary potassium restriction. AKT deletion impaired potassium conservation, reduced kidney growth and proximal tubular transport function, and promoted a shift from anabolic to catabolic renal metabolism. These changes were accompanied by glycosuria and systemic metabolic alterations, including lower fasting glucose levels, improved glucose tolerance, and enhanced insulin sensitivity.","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":"24 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088862","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":"Clinical Relevance of Donor-Derived Cell-Free DNA in Monitoring Kidney Transplant Rejection.","authors":"Angelica Pagliazzi, Karolien Wellekens, Henriette de Loor, Priyanka Koshy, Thibaut Vaulet, Arthur Vranken, Thomas Vanhoutte, Dirk Kuypers, Borefore Jallah, Tatjana Jatsenko, Paul Kyle, Robert Woodward, Maarten Coemans, Maarten Naesens","doi":"10.1681/ASN.0000001116","DOIUrl":"10.1681/ASN.0000001116","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;Donor-derived cell-free DNA showed strong discriminative ability for rejection after kidney transplantation. Clinical interpretability was improved by calculating donor-derived cell-free DNA result-specific likelihood ratio and corresponding post-test rejection risk. We showed that donor-derived cell-free DNA testing could help reduce unnecessary kidney biopsies, delineating a key clinical context in a low rejection prevalence cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Over the past 25 years, donor-derived cell-free DNA (dd-cfDNA) has emerged as a noninvasive biomarker for detecting allograft rejection in kidney transplant recipients, yet its clinical interpretability and context(s) of use in post-transplant monitoring remain largely unexplored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this observational cohort study, we analyzed 472 retrospective and 450 prospective plasma samples as the derivation and validation cohorts, respectively. Samples were collected at the time of either an indication or a protocol kidney biopsy. We evaluated three logistic regression models for rejection discrimination: a clinical model, the dd-cfDNA alone, and their combination. Result-specific likelihood ratios were derived from the dd-cfDNA-based model probabilities and applied to the clinical model predictions to obtain post-test probabilities of rejection. By comparing pre-test and post-test probabilities, we assessed the impact of dd-cfDNA on rejection risk stratification.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;dd-cfDNA alone demonstrated strong discriminative ability, with area under the receiver operating characteristic curves of 0.79 (95% confidence interval, 0.73 to 0.84) and 0.80 (95% confidence interval, 0.72 to 0.87) in the derivation and validation cohorts, respectively. Combining dd-cfDNA with clinical parameters improved the above area under the receiver operating characteristic curves to 0.82 and 0.87, respectively. We compared pre-test and post-test probabilities to determine how dd-cfDNA testing influenced rejection risk estimation. Incorporating dd-cfDNA testing results clarified risk stratification by reducing the number of samples categorized as intermediate (10%-30%) pre-test risk. Overall, 253/345 pre-test intermediate risk samples were reclassified, with 117/162 (72%) and 33/91 (36%) correctly assigned to low (≤10%) and high (≥30%) post-test risk, respectively. With 10% probability threshold for warranting a kidney biopsy, 482 biopsies would have been safely avoided using post-test probabilities, with 437 (91%) of these being protocol biopsies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our study confirmed the strong association between dd-cfDNA% and rejection after kidney transplantation. Using test result-specific likelihood ratio, we evaluated the impact of integrating dd-cfDNA% for estimating time point-specific rejection risk, demonstrating its potential to reduce the number of unnecessary biopsies in a cohort with a relatively","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2262-2274"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941466","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":"Executive Summary of the ASN Kidney Health Guidance on the Cardiovascular‑Kidney‑Metabolic Syndrome.","authors":"Sankar D Navaneethan, Brian Rifkin, Amy K Mottl","doi":"10.1681/ASN.0000001230","DOIUrl":"10.1681/ASN.0000001230","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Key points: &lt;/strong&gt;The cardiovascular‑kidney‑metabolic framework encourages routine assessment of cardiovascular risk, metabolic health, and kidney function. Cardiovascular risk equations should be used in patients with CKD to direct preventive therapies and promote coordination of care to optimize outcomes. Comprehensive therapy building upon foundational CKD management is essential to minimize treatment gaps and improve cardiovascular‑kidney‑metabolic outcomes.&lt;/p&gt;&lt;p&gt;&lt;p&gt;The recent release of the inaugural AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome calls for health care professionals across disciplines to broaden their practice to include the full spectrum of these interconnected disease states. This ASN Kidney Health Guidance aims to unite the nephrology community in this effort, highlighting the central role kidney disease plays in CKM syndrome and providing CKD-specific considerations. CKD is often complicated by comorbid cardiovascular and metabolic diseases, and regular evaluation of patients should include screening and management across disease states. The Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equation should be integrated along with kidney outcome predictors for routine patient counseling and risk assessment. Lifestyle modifications, including regular physical activity, avoidance of tobacco products, and adoption of a healthy diet and sleep patterns, underpin CKM management. Both renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 inhibitors are foundational therapies in CKD for the prevention of cardiovascular and kidney end points, and glucagon-like peptide-1-based therapies and nonsteroidal mineralocorticoid receptor antagonists may be added according to an individual patient's cardiovascular and metabolic risk profile. CKM therapies may be initiated simultaneously or in rapid sequence according to shared decision making, but therapeutic inertia must be avoided. Cardiovascular disease mitigation should also include lipid management for primary and secondary prevention. Evidence supporting the benefits of CKM treatments in people with glomerulonephritis, those with kidney transplant, those on dialysis with kidney failure treated with maintenance dialysis, pediatric populations, older adults, and those with frailty is limited. However, screening and diagnosis of CKM syndrome are critical, and these cardiokidney protective therapies may be used with shared decision making. Diabetes and obesity are extremely common in people living with kidney disease; both are major contributors to CKD progression. CKD poses a major risk of cardiovascular morbidity and mortality. Hence, nephrology team members should play a vital role in the diagnosis, treatment, and implementation of a holistic and multidisciplinary approach for the well-being of patients with kidney diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Podcast: &lt;/strong&gt;Thi","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2278-2281"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881059","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":"Selective Immune Reprogramming or Broad Immune Ablation with BCMA-CD19 Dual-Targeted CAR- T Cells in AL Amyloidosis.","authors":"Amir Muhammad, Muhammad Usman Janjua, Ling Yuan, Xiangcheng Xiao","doi":"10.1681/ASN.0000001138","DOIUrl":"10.1681/ASN.0000001138","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2353-2354"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143773","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":"Interpreting Policy Effects on Multidisciplinary Kidney Care: Autoregressive Integrated Moving Average Diagnostics and the Late Referral Denominator.","authors":"Yi Hua, Jiabao Liu, Sihan Chen, Yixuan Ma","doi":"10.1681/ASN.0000001148","DOIUrl":"10.1681/ASN.0000001148","url":null,"abstract":"","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2345"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176146","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":"Integrating Genomics and Proteomics to Identify Causal Proteins and Biologic Pathways for Incident Atrial Fibrillation in CKD.","authors":"Adrian M Petzl, Yue Ren, Faye L Norby, Jianqiao Wang, Ruth F Dubin, Izabele Antanavicius, Mark R Segal, Lin Yee Chen, Alvaro Alonso, Eugene P Rhee, Nisha Bansal, Paul L Kimmel, Ramachandran S Vasan, Aditya Surapaneni, Morgan E Grams, Harold Feldman, Francis E Marchlinski, Alan S Go, Hongzhe Lee, Peter Ganz, Rajat Deo","doi":"10.1681/ASN.0000001117","DOIUrl":"10.1681/ASN.0000001117","url":null,"abstract":"<p><strong>Key points: </strong>Using proteomics and Mendelian randomization, we identified causal proteins for the development of atrial fibrillation in patients with CKD. Immunologic function, cell growth, and neural development were common biologic pathways underlying atrial fibrillation and left atrial enlargement. Machine learning led to a nine-protein risk model that had a similar predictive performance for incident atrial fibrillation as clinical risk scores.</p><p><strong>Background: </strong>CKD is strongly associated with atrial fibrillation. Understanding the biologic pathways for this association and creating predictive models have been challenging. Left atrial enlargement is a substrate for atrial fibrillation, but any overlap between biomarkers of atrial fibrillation and left atrial enlargement in patients with CKD is unknown.</p><p><strong>Methods: </strong>We evaluated 4590 plasma proteins with SomaScan in two cohorts of adult patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC; n =2654) and the Atherosclerosis Risk in Communities cohort (ARIC; n =1326). Using Mendelian randomization, we identified proteins along the causal pathway to atrial fibrillation. We also identified proteins and corresponding pathways associated with larger echocardiographic left atrial size, a recognized substrate for atrial fibrillation. Finally, we developed and validated a multiprotein risk score for incident atrial fibrillation in the CKD population.</p><p><strong>Results: </strong>Over 5 years, incident atrial fibrillation occurred among 150 patients in the CRIC and 140 in the ARIC cohort. We identified three proteins causally linked to incident atrial fibrillation: neural EGF like‑like protein 1, cartilage intermediate layer protein 2, and matrix metallopeptidase 12. Pathway analysis revealed an overlap in eight of the top ten canonical pathways for incident atrial fibrillation and left atrial enlargement. A risk model for incident atrial fibrillation composed of proteins had annualized areas under the receiver-operating characteristic curve over 5 years ranging from 0.65 to 0.76, a performance similar to the Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF) clinical risk score.</p><p><strong>Conclusions: </strong>This study identified causal proteins and biologic mechanisms underlying incident atrial fibrillation in CKD. A proteomic risk score for incident atrial fibrillation in CKD performed similarly to the CHARGE-AF clinical risk score.</p>","PeriodicalId":17217,"journal":{"name":"Journal of The American Society of Nephrology","volume":" ","pages":"2194-2209"},"PeriodicalIF":9.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816571","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}