{"title":"PDGFRβ CAR T cells improve fibrosis in kidney disease models","authors":"Monica Wang","doi":"10.1038/s41581-025-01012-6","DOIUrl":"10.1038/s41581-025-01012-6","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 11","pages":"725-725"},"PeriodicalIF":39.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153422","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}
Matthijs Kox,Michael Bauer,Lieuwe D J Bos,Hjalmar Bouma,Thierry Calandra,Carolyn S Calfee,Benjamin G Chousterman,Lennie P G Derde,Evangelos J Giamarellos-Bourboulis,Hernando Gómez,Mihai G Netea,Marlies Ostermann,Tom van der Poll,Brendon P Scicluna,Christopher Seymour,Manu Shankar-Hari,Nathan Shapiro,Mervyn Singer,Fabienne Venet,Alexander P J Vlaar,Lonneke A van Vught,Sebastian Weis,W Joost Wiersinga,Peter Pickkers
{"title":"The immunology of sepsis: translating new insights into clinical practice.","authors":"Matthijs Kox,Michael Bauer,Lieuwe D J Bos,Hjalmar Bouma,Thierry Calandra,Carolyn S Calfee,Benjamin G Chousterman,Lennie P G Derde,Evangelos J Giamarellos-Bourboulis,Hernando Gómez,Mihai G Netea,Marlies Ostermann,Tom van der Poll,Brendon P Scicluna,Christopher Seymour,Manu Shankar-Hari,Nathan Shapiro,Mervyn Singer,Fabienne Venet,Alexander P J Vlaar,Lonneke A van Vught,Sebastian Weis,W Joost Wiersinga,Peter Pickkers","doi":"10.1038/s41581-025-01004-6","DOIUrl":"https://doi.org/10.1038/s41581-025-01004-6","url":null,"abstract":"Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Treatments that influence this dysregulated host response are sparse. The immunopathophysiology of sepsis entails overzealous inflammation causing acute organ dysfunction, as well as a profound and/or persistent anti-inflammatory response that increases susceptibility to secondary infection. The immune response in sepsis is under the influence of various endogenous and exogenous factors, including genetic makeup, age, sex, comorbidities, metabolism, prior microbial exposure and medications. The consequent heterogeneity of the syndrome hampers immunomodulatory treatment strategies that rely on a 'one-size-fits-all' approach. A precision medicine approach is therefore warranted. Balanced application of prognostic- and predictive-enrichment strategies is instrumental to achieve precision medicine. Phenotyping of patients using clinical, physiological, microbiological and/or molecular ('omics') data enables the identification of more homogeneous patient subgroups. Several studies suggest that such approaches can be used to tailor adjunctive immunomodulatory therapies in patients with sepsis. As well as repurposing existing drugs to treat sepsis, new drugs aimed at restoring immune homeostasis are under investigation. New clinical trial methodologies, including flexible platform trials, Bayesian statistics and embedding trials in health care systems are increasingly being used to keep pace with rapid developments in the field of sepsis immunobiology and ultimately to improve clinical outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"3 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134027","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}
Griet Glorieux, Stéphane Burtey, Pieter Evenepoel, Joachim Jankowski, Laetitia Koppe, Rosalinde Masereeuw, Raymond Vanholder
{"title":"A guide to uraemic toxicity.","authors":"Griet Glorieux, Stéphane Burtey, Pieter Evenepoel, Joachim Jankowski, Laetitia Koppe, Rosalinde Masereeuw, Raymond Vanholder","doi":"10.1038/s41581-025-01006-4","DOIUrl":"https://doi.org/10.1038/s41581-025-01006-4","url":null,"abstract":"<p><p>When kidney function is compromised, myriad metabolites and peptides - uraemic retention molecules (URMs) - accumulate in the body and compromise homeostasis. Over 150 molecules have been classified as URMs but omics approaches are revealing many more. When URMs exert pathophysiological effects and/or are associated with relevant adverse patient outcomes, they are called uraemic toxins. The origins of uraemic toxins and their contributions to post-translational modification of proteins are important current areas of research. Although most research has thus far focused on uraemic toxins, new studies have also identified URMs with the potential to counteract harmful biological changes that might thus confer a beneficial effect. To tackle the growing burden of chronic kidney disease, preventive therapeutic measures must target the disease early in its course and a balanced view of uraemic retention is needed to understand the role of URMs in kidney disease progression. Knowledge of the origin of the solutes, their kinetics, context-dependent biological profile and the involvement of transporter-mediated interorgan communication by small molecules - termed 'remote sensing and signalling' - is indispensable to facilitate the development of interventions that can promote or restore homeostasis in people with kidney dysfunction.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":39.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131653","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}
Urmila Anandh, Hans-Joachim Anders, Justine Bacchetta, David W Johnson, Valerie Luyckx, Giuseppe Remuzzi, Bernardo Rodriguez-Iturbe, Katalin Susztak, Katherine Tuttle, Motoko Yanagita
{"title":"Two decades of nephrology research: progress and future challenges","authors":"Urmila Anandh, Hans-Joachim Anders, Justine Bacchetta, David W Johnson, Valerie Luyckx, Giuseppe Remuzzi, Bernardo Rodriguez-Iturbe, Katalin Susztak, Katherine Tuttle, Motoko Yanagita","doi":"10.1038/s41581-025-00996-5","DOIUrl":"10.1038/s41581-025-00996-5","url":null,"abstract":"Since publication of the first issue of Nature Reviews Nephrology 20 years ago, advances across various subspecialities of nephrology have provided insights into disease processes and led to the development of new therapeutics for people with kidney disease. However, despite this progress, many kidney diseases remain untreatable, the costs of kidney disease care are immense, and vast inequities persist in disease burden and access to care. In this Viewpoint, we ask experts from several key subspecialties of nephrology to reflect on progress made over the past 20 years, remaining challenges and the steps needed to move the field forward.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 11","pages":"727-735"},"PeriodicalIF":39.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089810","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 changing landscape of kidney health and disease in Africa","authors":"Ifeoma I. Ulasi, Ugochi C. Onu","doi":"10.1038/s41581-025-01009-1","DOIUrl":"10.1038/s41581-025-01009-1","url":null,"abstract":"Africa has a high prevalence of chronic kidney disease (CKD), but efforts to address this burden lag behind those of high-income regions. In the past 20 years, progress has been made in collaborative efforts to share clinical and diagnostic skills and better define the epidemiology and pathophysiology of CKD in Africa.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 11","pages":"720-721"},"PeriodicalIF":39.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077736","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":"Guidelines for the use of economic evaluation to inform policies around access to treatment for kidney failure","authors":"Siobhan Botwright, Panji Fortuna Hadisoemarto, Kinanti Khansa Chavarina, Aye Nandar Myint, Brandon Wen Bing Chua, Kridsada Chareonrungrueangchai, Chotika Suwanpanich, Pitsinee Supapol, Ijeoma Edoka, Valerie Luyckx, Martin I. Meltzer, Yot Teerawattananon","doi":"10.1038/s41581-025-01000-w","DOIUrl":"https://doi.org/10.1038/s41581-025-01000-w","url":null,"abstract":"<p>Kidney failure is the most advanced stage of chronic kidney disease, at which point patients require kidney replacement therapy (KRT) in the form of kidney transplant or lifelong dialysis to survive. Although many governments seek to provide KRT for patients with kidney failure under publicly funded health schemes, KRT requires considerable financial and human resources, which may need to be diverted from other health programmes. In deciding which KRT services to provide, to whom, and under which conditions, economic evaluation can show the trade-off between the cost and benefit of different policy options. This Guideline has been written for nephrologists, clinicians and policymakers, to build confidence in requesting, contributing towards, and using the results from economic evaluation studies. It is aimed at outlining the cases in which economic evaluation may support KRT policymaking and to lay out good practice for economic evaluation of KRT services. Recommendations cover the process of developing the policy and research questions, conducting the economic evaluation and interpreting results for policy.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"33 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031720","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}
Hannah M. L. Young, Roseanne E. Billany, Matthew P. M. Graham-Brown, Courtney J. Lightfoot, Daniel S. March, Alice C. Smith
{"title":"Physical activity in kidney disease: evidence and implementation","authors":"Hannah M. L. Young, Roseanne E. Billany, Matthew P. M. Graham-Brown, Courtney J. Lightfoot, Daniel S. March, Alice C. Smith","doi":"10.1038/s41581-025-00999-2","DOIUrl":"https://doi.org/10.1038/s41581-025-00999-2","url":null,"abstract":"<p>Despite over 30 years of research and guidelines promoting physical activity for people living with chronic kidney disease (CKD), widespread implementation of physical activity in routine care remains low worldwide. Consequently, the population with CKD remains highly inactive across all stages of the disease. Randomized controlled trials in people with CKD, people on dialysis and kidney transplant recipients consistently show that structured exercise is safe and can improve physical function, cardiorespiratory fitness, muscle strength and aspects of quality of life. However, these trials are of variable quality with modest sample sizes in some groups, and a need exists for larger, implementation-focused studies. Evidence generation in CKD has often been disconnected from service development, limiting workforce skills, resources and pathways for delivery. To achieve meaningful change, research must be designed with implementation in mind, using frameworks that consider context, sustainability and stakeholder involvement. Digital solutions and approaches targeting 24-h movement behaviours may extend the reach of physical-activity interventions, but barriers such as health-professional training, patient capability and system-level prioritization must be addressed. Embedding physical activity in clinical care offers a clear opportunity to improve outcomes and quality of life for people living with CKD.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"100 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031719","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":"Green nephrology: from evidence to action","authors":"Katherine A. Barraclough, Karin G. F. Gerritsen","doi":"10.1038/s41581-025-01005-5","DOIUrl":"10.1038/s41581-025-01005-5","url":null,"abstract":"In the past 20 years, awareness of the huge environmental impact of kidney care has increased considerably. Although opportunities to reduce this impact have been identified and innovative approaches developed, implementation of these strategies remains slow. System-wide action is urgently required to improve the sustainability of kidney care.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 11","pages":"722-723"},"PeriodicalIF":39.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035229","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}
James Hunter, Sarah Hosgood, Cyril Moers, Henri Leuvenink, Ton J. Rabelink, Rutger Ploeg
{"title":"Improving outcomes in kidney transplantation through advances in donor organ perfusion","authors":"James Hunter, Sarah Hosgood, Cyril Moers, Henri Leuvenink, Ton J. Rabelink, Rutger Ploeg","doi":"10.1038/s41581-025-00993-8","DOIUrl":"https://doi.org/10.1038/s41581-025-00993-8","url":null,"abstract":"<p>The global shortage of suitable donor kidneys is the primary challenge in kidney transplantation, and it is exacerbated by ageing donors with increased numbers of health issues. Improving organ assessment, preservation and conditioning could enhance organ utilization and patient outcomes. Hypothermic machine perfusion (HMP) is associated with better results than static cold storage by reducing delayed graft function and improving short-term graft survival, especially in kidneys recovered from marginal-quality donors. Although HMP is useful for organ preservation, it is difficult to assess organ viability during HMP because of the reduced metabolic activity at low temperatures, and the adoption of HMP has faced logistical challenges. The addition of oxygen during HMP is aimed at reducing ischaemia–reperfusion injury, but has shown mixed results in kidney transplantation, often depending on the duration of perfusion, although some studies found that the addition of oxygen improved outcomes in higher-risk donors. Normothermic machine perfusion helps to restore kidney function by delivering oxygen and nutrients at body temperature, potentially reducing ischaemia–reperfusion injury. Early studies suggest its safety, but clinical benefits remain unproven. Normothermic machine perfusion also holds promise for assessing organ viability pre-transplantation by enabling real-time evaluation. In this Review, we will summarize the different methods of kidney preservation, providing details of the effect that each method has on graft and patient outcomes and the strengths and limitations of each method.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"35 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017619","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":"Lived experience and empathy: lessons learned as a nephrologist with kidney disease","authors":"Ken Sutha","doi":"10.1038/s41581-025-01003-7","DOIUrl":"https://doi.org/10.1038/s41581-025-01003-7","url":null,"abstract":"Diagnoses and decisions that we encounter nearly every day as nephrologists are often life-changing for patients. Sometimes, when more than one potential course of action exists, we must give our patients grace and time, allowing them agency in coming to a medically safe shared decision.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"42 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995498","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}