Nature Reviews Nephrology最新文献

{"title":"Insights from integrative spatial transcriptomics in sepsis-associated acute kidney injury","authors":"Moritz Uhlig, David Schumacher, Gernot Marx, Claudia Seikrit, Kai M. Schmidt-Ott, Turgay Saritas, Rafael Kramann","doi":"10.1038/s41581-026-01107-8","DOIUrl":"10.1038/s41581-026-01107-8","url":null,"abstract":"Sepsis-associated acute kidney injury (SA-AKI) remains a frequent and life-threatening complication of sepsis, yet its pathophysiology is still not fully understood, owing to the complex interplay of immune, vascular and parenchymal responses. Closing this knowledge gap is essential for developing urgently needed targeted therapies. Although bulk and single-cell transcriptomics, as well as proteomic approaches, have advanced our understanding of the molecular mechanisms involved in SA-AKI, they lack the spatial context required to fully interpret tissue heterogeneity and microenvironmental changes. The integration of high-resolution spatial transcriptomics with single-cell RNA sequencing and other multi-omics approaches offers a novel lens through which to dissect the cellular and molecular architecture of septic kidneys. In SA-AKI, discrete inflammatory, vascular and tubular niches can cause substantial functional impairment even though global histological changes may be much milder. Integrative spatial transcriptomics localizes pathological signalling and how it is transmitted across immune, endothelial and epithelial cells. By resolving niche-specific crosstalk, these approaches might highlight druggable pathways and lead to the identification of clinical biomarker candidates. These insights, in turn, facilitate the identification of mechanistic endotypes that align more closely with prognosis than with conventional staging. Importantly, translation into clinical trials will require standardized endotype definitions, endotype validation and standardized sampling strategies, as well as scalable analytical pipelines to enable endotype identification at the bedside. The complexity of the host responses that underlie sepsis-associated acute kidney injury (SA-AKI) complicates patient management and contributes to its high mortality. Here, the authors examine insights into the pathophysiology of SA-AKI gained from the integration of high-resolution spatial transcriptomics with other multi-omics approaches, and consider how these technologies might enable targeted therapeutic interventions.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 11","pages":"803-820"},"PeriodicalIF":46.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605655","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":"Epigenetic regulation of kidney development","authors":"Samir S. El-Dahr, Jordan Kreidberg","doi":"10.1038/s41581-026-01105-w","DOIUrl":"10.1038/s41581-026-01105-w","url":null,"abstract":"The methylation or demethylation of genomic DNA at specific locations and the diverse array of post-translational modifications of histones associated with genomic DNA are collectively known as epigenetic modifications, so-called because they affect chromatin structure but do not affect the actual DNA sequence of the genome. Nevertheless, post-translational modifications of histones, including methylation, acetylation, phosphorylation and ubiquitination, as well as the methylation and subsequent de-methylation of genomic DNA, can profoundly affect gene expression. Nowhere has the study of epigenetically regulated gene expression had such impact as on our understanding of organism development. In the developing kidney, epigenetic-based regulation affects the cell fate decisions of stem-like nephron progenitor cells (NPCs). Changes in chromatin accessibility at the loci of genes associated with NPC self-renewal and nephron differentiation — in part driven by transcription factors known to regulate kidney development — affect the differentiation of NPCs into precursors of the nephron such as the pretubular aggregate and renal vesicle, and the subsequent differentiation of various segments of the mature nephron. Epigenetic mechanisms also contribute to the process of NPC ageing and the cessation of nephrogenesis, with consequences for nephron endowment and kidney function. This Review describes current understanding of the epigenetic regulation of kidney development. It describes the epigenetic drivers of cell fate decisions made by nephron progenitor cells, the chromatin landscape of accessible regulatory elements that orchestrate these decisions, and the functional consequences for congenital kidney diseases and the programming of adult kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 10","pages":"739-751"},"PeriodicalIF":46.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605696","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":"Nephrology care for incarcerated people: a call to action","authors":"Laura J. Maursetter","doi":"10.1038/s41581-026-01108-7","DOIUrl":"10.1038/s41581-026-01108-7","url":null,"abstract":"The carceral system has the impossible task of providing appropriate care for a vulnerable population while limiting taxpayer spending. Although many risk factors for incarceration also increase the risk of chronic kidney disease (CKD), specific CKD screening requirements or treatment accountability are lacking, which compromises patient care.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 10","pages":"671-672"},"PeriodicalIF":46.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605659","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":"WNT organizers control nephron patterning in organoids","authors":"Susan J. Allison","doi":"10.1038/s41581-026-01113-w","DOIUrl":"10.1038/s41581-026-01113-w","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 9","pages":"600-600"},"PeriodicalIF":46.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605704","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 first-in-human combined bladder and kidney transplant","authors":"Ellen F. Carney","doi":"10.1038/s41581-026-01114-9","DOIUrl":"10.1038/s41581-026-01114-9","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 9","pages":"601-601"},"PeriodicalIF":46.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605620","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":"Beyond paediatric nephrology: gaps in care for young adults","authors":"Michael Rauchman, Carmen M. Halabi","doi":"10.1038/s41581-026-01110-z","DOIUrl":"10.1038/s41581-026-01110-z","url":null,"abstract":"The prevalence of kidney disease is increasing in children and young adults, who face a lifetime of chronic disease with considerable morbidity and mortality. However, a critical shortage in the paediatric nephrology workforce and deficiencies in paediatric-to-adult transition care mean that we fail to meet the needs of this vulnerable population. Paediatric and adult nephrologists need to take collaborative action to address this crisis.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 10","pages":"675-676"},"PeriodicalIF":46.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585021","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":"Disease modification in lupus nephritis: towards a pathophysiology-based treatment paradigm","authors":"Mieke van Schaik, Cees van Kooten, Laurent Arnaud, Annette Bruchfeld, Fernando Caravaca-Fontán, Gema M. Fernandez Juarez, Jürgen Floege, Ana Malvar, Safak Mirioglu, Sarah Moran, Ioannis Parodis, Luis F. Quintana, Brad H. Rovin, Stefanie Steiger, Kate Stevens, Andreas Kronbichler, Y. K. Onno Teng, Eleni Frangou, on behalf of the European Renal Association (ERA) Immunonephrology Working Group (IWG)","doi":"10.1038/s41581-026-01103-y","DOIUrl":"10.1038/s41581-026-01103-y","url":null,"abstract":"Glucocorticoids and antiproliferative agents, such as mycophenolate and cyclophosphamide, form the backbone of current therapy for lupus nephritis. Despite their ability to suppress inflammation, such treatments are often limited by their incomplete efficacy, substantial toxicity and failure to prevent disease progression. Many patients continue to relapse and accumulate kidney damage, underscoring the urgent need for new strategies. Advances in our understanding of the pathophysiology of lupus nephritis have provided insights into the mechanisms by which the impaired clearance of nuclear self-antigens drives innate immune activation, including excessive Toll-like receptor signalling, interferon pathway upregulation and B cell hyperactivation. These processes sustain autoantibody production and complement activation and contribute to progressive tissue injury. Emerging immunomodulatory therapies that are designed to target these pathways have the potential to restore immune balance, dampen systemic inflammation and protect the kidneys. These developments pave the way for a new treatment paradigm that focuses on disease modification, enabling early prevention of inflammation-driven kidney injury and protecting against disease progression. Fast-acting glucocorticoids and classic antiproliferative agents can be used to rapidly control systemic inflammation, although the early addition of immunomodulatory drugs is critical to promote sustained remission and prevent kidney damage. Integrated into a multitargeted, pathophysiology-based and personalized approach, this paradigm represents a departure from the conventional trial-and-error strategy of therapeutic switching and add-on regimens, and instead provides a more precise and effective framework for optimizing and individualizing disease management. This Review provides an overview of the pathophysiology of systemic lupus erythematosus as well as drugs that have been developed to target these pathophysiological processes. The authors also synthesize a translational approach aimed at enabling disease modification in lupus nephritis through the integration of glucocorticoids and conventional antiproliferative agents with immunomodulatory drugs.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 10","pages":"684-703"},"PeriodicalIF":46.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579503","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":"Thymic health and implications for chronic kidney disease","authors":"Michiel G. H. Betjes, Nicolle H. R. Litjens","doi":"10.1038/s41581-026-01104-x","DOIUrl":"10.1038/s41581-026-01104-x","url":null,"abstract":"The thymus is essential for T cell development and a decline in thymic health or a thymectomy therefore have profound clinical implications. Loss of thymic function might contribute to the uraemia-associated ageing of the T cell compartment, and new research is needed to clarify potential underlying mechanisms and effects on patient outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 9","pages":"593-594"},"PeriodicalIF":46.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459633","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":"Oscars’ inclusion standards for kidney trials","authors":"Rathika Krishnasamy","doi":"10.1038/s41581-026-01106-9","DOIUrl":"10.1038/s41581-026-01106-9","url":null,"abstract":"Despite growing awareness of inequities in kidney research, high-impact trials remain predominantly led by men from high-income countries, and important disparities persist in the recruitment of women and populations disproportionately affected by chronic kidney disease. It is time to move beyond acknowledgement of such disparities and commit to inclusion standards that systemically transform kidney research.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 9","pages":"591-592"},"PeriodicalIF":46.7,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451591","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 kidney distal tubule potassium switch, modern diet and hypertension","authors":"Paul A. Welling, Eric Delpire, David H. Ellison, Olivier Staub, Michael Stowasser, Robert A. Fenton","doi":"10.1038/s41581-026-01099-5","DOIUrl":"10.1038/s41581-026-01099-5","url":null,"abstract":"Hypertension is the leading contributor to premature death and disability in the world. Genetic susceptibility and high dietary salt (NaCl) consumption have long been considered to be the primary culprits but growing evidence indicates that low dietary potassium consumption has an equally important role. Although the underlying mechanisms are complex and multifactorial, the potassium switch signalling mechanism in the kidney distal convoluted tubule represents a crucial pathway with implications for preventing and treating hypertension. Comprising a Kir4.1 and Kir5.1 channel potassium-sensing mechanism, a WNK kinase-induced phosphorylation cascade, and the thiazide-diuretic-targeted sodium chloride co-transporter, the potassium switch orchestrates a physiological response in the distal nephron that maintains sodium–potassium balance over wide variations in dietary potassium intake. The potassium switch is ideally adapted for the low-salt, feast-and-famine diets of hunter-gatherers. However, low potassium consumption, which is common in high-sodium modern diets, promotes potassium conservation at the expense of increasing sodium reabsorption, exacerbating salt-sensitive hypertension and its associated cardiovascular complications. Here, we discuss current understanding of the potassium switch and how its role in kidney adaptation to the modern diet can contribute to hypertension. This Review focuses on the potassium switch signalling pathway and its regulation of urinary sodium excretion according to plasma potassium levels. Welling and colleagues examine how this pathway affects the interplay between potassium intake, salt handling in the kidney and blood pressure, and its implications for dietary interventions for blood pressure control.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 10","pages":"721-738"},"PeriodicalIF":46.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432053","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}