Seminars in nephrology最新文献

{"title":"A Holistic Approach to AKI: Integrating Clinical and Molecular Data in the Human Kidney.","authors":"Jennifer A Schaub, Mathew Alaba, Matthias Kretzler","doi":"10.1016/j.semnephrol.2025.151663","DOIUrl":"10.1016/j.semnephrol.2025.151663","url":null,"abstract":"<p><p>Despite intensive research efforts, acute kidney injury (AKI) is a common clinical syndrome that has limited treatment options apart from supportive care. The increasing availability of molecular interrogation data from patients with Acute Kidney Injury provides an unparalleled opportunity to leverage systems biology approaches. In this review, we discuss the challenges with AKI research, explain how systems biology approaches can link molecular data to clinical phenotypes, review available molecular interrogation tools and techniques, and provide examples where systems biology approaches have been successfully applied in nephrology. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.</p>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":" ","pages":"151663"},"PeriodicalIF":3.5,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Environmental Heat Exposure Is a Risk Factor for Acute Kidney Injury and Chronic Kidney Disease.","authors":"Hung Nguyen, Bryan K Becker, Subhashini Bolisetty, Malgorzata Kasztan, Paul W Sanders, Kelly A Hyndman","doi":"10.1016/j.semnephrol.2025.151664","DOIUrl":"https://doi.org/10.1016/j.semnephrol.2025.151664","url":null,"abstract":"<p><p>Chronic kidney disease of unknown etiology has been reported in Mesoamerican regions and other parts of the world, with increasing evidence pointing to heat stress as a central contributing factor. The incidence of acute kidney injury appears to correlate strongly with heat exposure, as demonstrated in both human and animal studies. The underlying mechanisms of heat-induced kidney injury are likely multifactorial, involving hemodynamic changes, immune responses, and possibly coagulopathies. However, the precise pathways remain unclear, highlighting the urgent need for a deeper understanding of the mechanisms and for developing strategies to prevent or mitigate renal damage. This is particularly important not only for heat-exposed occupational groups, such as agricultural workers, military personnel, and athletes, but also for the general population, who are increasingly vulnerable to extreme heat events every year. Semin Nephrol 36:x-xx © 20XX Elsevier Inc. All rights reserved.</p>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":" ","pages":"151664"},"PeriodicalIF":3.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using Large Genomic Biobanks to Generate Insights into Genetic Kidney Disease","authors":"Alexander R. Chang MD, MS ,&nbsp;Janewit Wongboonsin MD, MS ,&nbsp;Andrew J. Mallett MBBS, MMed, PhD ,&nbsp;Ana Morales MS, CGC ,&nbsp;Kyle Retterer MS ,&nbsp;Tooraj Mirshahi PhD ,&nbsp;John A. Sayer MB, ChB, PhD","doi":"10.1016/j.semnephrol.2025.151651","DOIUrl":"10.1016/j.semnephrol.2025.151651","url":null,"abstract":"<div><div><span><span>Chronic kidney disease (CKD) affects approximately 9% of the global population, leading to increased risks of end-stage kidney disease (ESKD), cardiovascular disease (CVD), and mortality. Patients with CKD are a huge burden on </span>health care resources globally. CKD is a complex condition influenced by a combination of </span>genetic<span><span>, environmental, and traditional risk factors. Family studies have suggested heritability<span> rates for CKD ranging from 30% to 75%, and large genomic biobank studies have proven essential in identifying genes with substantial effects on CKD risk and in capturing cumulative genetic risk through polygenic risk scores. These biobanks are crucial for discovering new genes associated with kidney health and disease, and their growing size enhances the power to detect novel genetic associations. Integrating multi-omics technologies such as transcriptomics<span>, metabolomics, and </span></span></span>proteomics<span> further enriches our understanding of CKD, while advanced computational tools continue to expand our insights into genetic data. Polygenic risk scores, derived from hundreds of genetic variants<span><span> with small effect sizes, can help identify individuals at high risk of CKD. Genomic biobanks offer valuable opportunities for early identification and personalized treatment of monogenic kidney disorders, such as </span>autosomal dominant polycystic kidney<span> disease and Alport syndrome. These biobanks help fill knowledge gaps, particularly in individuals with milder or asymptomatic presentations who are often underrepresented in traditional studies. Expanding genomic biobank efforts globally, especially in diverse populations, is vital to enhancing our understanding of the genetic underpinnings of kidney disease. This review highlights the significant contributions of genomic biobanks to advancing our comprehension of the genetics of CKD.</span></span></span></span></div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151651"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Genetics Into the Design and Conduct of Clinical Trials in Nephrology","authors":"Justyna E. Ozimek-Kulik ,&nbsp;Nicholas G. Larkins ,&nbsp;Gopi K. Rangan ,&nbsp;Hugh J. McCarthy","doi":"10.1016/j.semnephrol.2025.151650","DOIUrl":"10.1016/j.semnephrol.2025.151650","url":null,"abstract":"<div><div>Advances in genomic diagnostics have enabled earlier and more precise identification of genetic kidney disease, but the translation of these insights into trial methodology and therapeutic development has lagged. This review examines the current challenges in nephrology trials—including disease heterogeneity, slow progression, and limited industry engagement—and explores how genomic information can address these barriers. Examples from trials in autosomal dominant polycystic kidney disease and other genetic kidney diseases demonstrate the feasibility and value of genomics-informed approaches, including genotype-based recruitment, <em>post hoc</em> genetic stratification, and drug repurposing. The emergence of genotype stratification, artificial intelligence tools, and gene-based therapies presents further opportunities to refine trial design and personalize treatment. However, incorporating genomics into clinical research also raises complex ethical and regulatory issues, including consent processes, data governance, and equitable access to testing and trial participation. As genomic testing becomes embedded in standard clinical practice, its alignment with clinical research infrastructure offers the potential to create a learning health system in nephrology. Realizing this potential will require cross-disciplinary coordination, international collaboration, and co-design with patients and communities. Integrating genetic nephrology into clinical trial conduct is not only feasible but essential to advancing precision medicine and improving outcomes for patients with kidney disease.</div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151650"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Nephrology – Key Foundations for Kidney Medicine","authors":"Janewit Wongboonsin,&nbsp;Andrew J. Mallett","doi":"10.1016/j.semnephrol.2025.151661","DOIUrl":"10.1016/j.semnephrol.2025.151661","url":null,"abstract":"","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151661"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Educating the Next-Generation Expert in Nephrology Genetics","authors":"Matthew B. Lanktree ,&nbsp;Shaymaa Shurrab ,&nbsp;Resham Ejaz ,&nbsp;Vanda McNiven ,&nbsp;Lauren Brick ,&nbsp;Nithiakishna Selvathesan ,&nbsp;Peter Margetts ,&nbsp;Azim Gangji ,&nbsp;Marie Pigeyre ,&nbsp;Alexander Chang ,&nbsp;Christie P. Thomas ,&nbsp;Mathieu Lemaire","doi":"10.1016/j.semnephrol.2025.151648","DOIUrl":"10.1016/j.semnephrol.2025.151648","url":null,"abstract":"<div><div>The importance of genetics and genomics in general nephrology has rapidly ascended within the last decade. While the genetic literacy of all nephrologists must improve, there is a particular need to develop the next generation of leaders and educators in nephrology genetics. In this review, we summarize how nephrology genetics could fit into the nephrology landscape and discuss components of a nephrology genetics training program. We outline potential objectives and educational content for a nephrology genetics curriculum. Finally, we identify logistical challenges and potential solutions when educating the next-generation expert in nephrology genetics.</div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151648"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complexities in Variant Analysis, Classification, and Interpretation in Kidney Disease–Related Genes","authors":"Maggie Westemeyer MS, CGC ,&nbsp;Michelle S. Bloom PhD ,&nbsp;Alicia B. Byrne PhD ,&nbsp;Vivek Charu MD, PhD","doi":"10.1016/j.semnephrol.2025.151646","DOIUrl":"10.1016/j.semnephrol.2025.151646","url":null,"abstract":"<div><div>Advancements in chronic kidney disease (CKD) genetic research and next-generation sequencing have improved CKD diagnosis and personalized treatment. Broad gene panel testing or whole exome/genome sequencing has greatly improved understanding of the genetic etiology of kidney disease but has also increased the complexity of interpretation. Standardized variant classification guidelines help, but challenges remain due to subjective evidence and limited functional and phenotypic data. Careful consideration of genetic and clinical evidence, along with collaboration between clinicians, genetics experts, and laboratories, is essential for accurate interpretation and patient care. This article examines nephrology genetic testing, focusing on the complexities of variant analysis, classification, and interpretation. Variant classification in monogenic kidney diseases is crucial for accurate diagnosis and patient management. We outline the classification methods highlighting several variant examples using the ACMG/AMP framework and quantitative approaches for pathogenicity assessment. We highlight challenges in integrating genetic findings into nephrology and emphasize the clinical impact of accurate genetic diagnoses for precision medicine in CKD.</div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151646"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Disease Relationships in Kidney Genetics","authors":"Vanessa Gitau BS ,&nbsp;Julie Ratliff BS, MPH ,&nbsp;Ryan Webb BS ,&nbsp;Andrew J. Mallett MD PhD ,&nbsp;Pamela Ajuyah PhD","doi":"10.1016/j.semnephrol.2025.151647","DOIUrl":"10.1016/j.semnephrol.2025.151647","url":null,"abstract":"<div><div>Genomic sequencing technologies are used in diagnostic laboratories to identify genetic causes of disease in patients. Gene curation plays an integral role by determining which genes have sufficient evidence for inclusion in diagnostic panels and those that should be prioritized in genome and exome sequencing. As the precursor to variant curation, gene curation also establishes pathogenicity limits for variant classification. Evaluating the clinical validity of a gene–disease relationship requires assessment of genetic and experimental evidence from literature and databases. The Clinical Genome Resource (ClinGen) has a semiquantitative framework for gene curation that is used across its Gene Curation Expert Panels (GCEPs). The ClinGen Kidney Disease Clinical Domain Working Group oversees five GCEPs covering the glomerulopathies, tubulopathies, complement-mediated kidney diseases, congenital anomalies of the kidney and urinary tract, and renal ciliopathies. These panels use a multidisciplinary approach in their gene curations, which are published and accessible to the public via the ClinGen website. ClinGen’s expert-informed curations and other resources outlined in this review will help nephrologists validate whether genetic findings in reports are clinically relevant to their patients. Empowering nephrologists with knowledge of gene curation principles is imperative for informed decision-making in patient care.</div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151647"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Models of Care for the Implementation of Genetic Testing in Nephrology","authors":"Dervla M. Connaughton MB, BCh, BAOI, LRCP&SI, MSc, PhD ,&nbsp;Andrew J. Mallett MBBS, MMed, PhD, CF, AFRACMA, FISN, FASN, FRCP, FRACP","doi":"10.1016/j.semnephrol.2025.151649","DOIUrl":"10.1016/j.semnephrol.2025.151649","url":null,"abstract":"<div><div>Genetic testing holds great potential to enhance the diagnosis and management of kidney disease, yet its integration into routine nephrology care remains limited and often delayed. Despite strong evidence supporting its clinical utility and cost effectiveness, significant barriers hinder its widespread adoption. This review examines care models designed to embed genetic testing into nephrology practice and proposes strategies to improve access for chronic kidney disease patients. Key approaches include enhancing clinical genetic services, establishing kidney genetics clinics, using technology such as virtual consultations, forming variant review boards and multidisciplinary teams, and mainstreaming genetic testing into nephrology care. For each model, the review identifies essential components for success and discusses barriers and facilitators to implementation. By focusing on practical, scalable, and patient-centered solutions, this review advocates for a paradigm shift in nephrology care. It envisions genetic testing as a standard component of kidney disease management, aiming to improve outcomes and promote equitable care for patients globally.</div></div>","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":"45 5","pages":"Article 151649"},"PeriodicalIF":3.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction: The 2025 American Society of Nephrology Third Acute Kidney Injury: Bench to Bedside Conference.","authors":"Kelly A Hyndman, Leah J Siskind, Mark de Caestecker","doi":"10.1016/j.semnephrol.2025.151662","DOIUrl":"https://doi.org/10.1016/j.semnephrol.2025.151662","url":null,"abstract":"","PeriodicalId":21756,"journal":{"name":"Seminars in nephrology","volume":" ","pages":"151662"},"PeriodicalIF":3.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}