Nature Reviews Nephrology最新文献_第8页

Insulin resistance and hyperinsulinaemia in kidney disease: mechanisms and metabolic effects 肾脏疾病中的胰岛素抵抗和高胰岛素血症：机制和代谢作用

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-25 DOI: 10.1038/s41581-026-01066-0

Hussein Zaitoon, Muhammad Abdul-Ghani, Ralph A. DeFronzo

{"title":"Insulin resistance and hyperinsulinaemia in kidney disease: mechanisms and metabolic effects","authors":"Hussein Zaitoon, Muhammad Abdul-Ghani, Ralph A. DeFronzo","doi":"10.1038/s41581-026-01066-0","DOIUrl":"10.1038/s41581-026-01066-0","url":null,"abstract":"The impact of insulin resistance and compensatory hyperinsulinaemia on kidney function, and their contribution to the development and progression of chronic kidney disease, have largely been overlooked in people with or without diabetes. Beyond its classical metabolic targets (muscle, liver and adipocytes), insulin has an essential role in kidney metabolism and physiology, regulating podocyte integrity, tubular sodium handling and gluconeogenesis. In states of insulin resistance, these homeostatic functions are disrupted, leading to glomerular hyperfiltration, proteinuria, sodium retention, progressive kidney injury and exacerbation of hyperglycaemia. Simultaneously, chronic hyperinsulinaemia activates pro-growth and pro-fibrotic pathways, resulting in vascular dysfunction, inflammation and fibrosis. The emerging framework of a cardiovascular–kidney–metabolic syndrome reframes kidney disease as a manifestation of systemic metabolic dysfunction with insulin resistance and impaired insulin signaling at its core. Here, we provide mechanistic insights linking insulin resistance, hyperinsulinaemia, lipotoxicity and inflammation to kidney pathology and highlight the therapeutic implications of this paradigm for renoprotective agents, including sodium–glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists and thiazolidinediones. Recognition of the pathogenic role of insulin resistance and hyperinsulinaemia will advance the development of novel therapeutic approaches to prevent and slow the progression of chronic kidney disease. Here, DeFronzo and colleagues explore the underappreciated adverse effects of insulin resistance and accompanying hyperinsulinaemia on the kidney, which is an insulin-responsive organ and has an important role in insulin homeostasis. The authors examine the interplay between insulin dysregulation, lipid metabolism and inflammation, and consider emerging therapies to address this metabolic dysfunction.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 7","pages":"474-486"},"PeriodicalIF":46.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506737","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}

引用次数: 0

Future needs for clinical trials in autosomal dominant polycystic kidney disease 未来常染色体显性多囊肾病的临床试验需求

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-24 DOI: 10.1038/s41581-026-01070-4

Karla M. Márquez-Nogueras, Ivana Y. Kuo, Arlene B. Chapman

引用次数: 0

The endothelium response to kidney injury 内皮细胞对肾损伤的反应。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-23 DOI: 10.1038/s41581-026-01067-z

Kyle H. Moore, Arin L. Melkonian, James F. George, Anupam Agarwal

{"title":"The endothelium response to kidney injury","authors":"Kyle H. Moore, Arin L. Melkonian, James F. George, Anupam Agarwal","doi":"10.1038/s41581-026-01067-z","DOIUrl":"10.1038/s41581-026-01067-z","url":null,"abstract":"The kidney contains a heterogeneous endothelial cell population, with each subset serving distinct roles in the maintenance of tissue homeostasis and support of kidney function. This diverse cellular population comprises three broad subsets: vascular, glomerular and lymphatic endothelia. The vascular endothelium, which in this context refers to all vascular endothelial cells apart from those in the glomeruli and lymph vessels, supports parenchymal cells by delivering oxygen and nutrients, removing metabolic waste and facilitating tubular secretion and reabsorption processes. Although similar, the glomerular endothelium is a highly specialized capillary system designed to maintain the glomerular filtration barrier by selectively permitting the passage of water and electrolytes into the tubular filtrate while preventing the passage of cells and large solutes. The lymphatic endothelium aids the reabsorption of extracellular fluid and trafficking of immune cells out of the kidney to draining lymph nodes. These kidney endothelial populations undergo marked changes following kidney injury, involving the increased production of inflammatory cytokines, reduced expression of angiogenic and vasodilatory molecules and loss of the glycocalyx, which can result in endothelial dysfunction, capillary rarefaction and impaired barrier function, and can influence outcomes towards recovery or progressive damage. Improved understanding and an ability to therapeutically target the kidney endothelium after injury may lead to improved care and outcomes in kidney disease. The kidney contains a heterogeneous endothelial cell population that serve distinct roles in the maintenance of tissue homeostasis and kidney function. This Review summarizes current understanding of the endothelial response to kidney injury, focusing on the response of vascular, glomerular and lymphatic endothelial cells in diverse kidney diseases, and describes the potential of emerging endothelium-targeted therapeutics to ameliorate injury and restore kidney function.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 6","pages":"422-437"},"PeriodicalIF":39.8,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502509","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}

引用次数: 0

Large language models in healthcare 医疗保健中的大型语言模型。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-23 DOI: 10.1038/s41581-026-01071-3

Daniel Truhn, Jakob Nikolas Kather

引用次数: 0

Working together to diagnose rare kidney disease earlier 共同努力及早诊断罕见的肾脏疾病。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-20 DOI: 10.1038/s41581-026-01069-x

Susie Gear

引用次数: 0

A path to reduce chronic kidney disease burden in Samoa 减少萨摩亚慢性肾脏疾病负担的途径。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-17 DOI: 10.1038/s41581-026-01068-y

Malama Tafuna’i, Robert Walker

引用次数: 0

‘Missing’ disease-causing variants in Alport syndrome 阿尔波特综合症中“缺失”的致病变异。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-11 DOI: 10.1038/s41581-026-01061-5

Judy Savige, Adam M. Bournazos, Tomoko Horinouchi, Bryony A. Thompson, Yanqin Zhang, Julia Hoefele, Mary Huang

{"title":"‘Missing’ disease-causing variants in Alport syndrome","authors":"Judy Savige, Adam M. Bournazos, Tomoko Horinouchi, Bryony A. Thompson, Yanqin Zhang, Julia Hoefele, Mary Huang","doi":"10.1038/s41581-026-01061-5","DOIUrl":"10.1038/s41581-026-01061-5","url":null,"abstract":"Up to 20% of people with clinically suspected Alport syndrome do not have a disease-causing variant identified with genetic testing. Disease-causing changes are ‘missing’ because the identified variant is of uncertain significance or no suspicious change has been found. A variant of uncertain significance might be resolved after a clinician–laboratory consultation, family segregation studies, functional assays, evidence from large case–control cohorts or review after further genetic and experimental information becomes available. Other explanations for a lack of disease-causing variants include the presence of phenocopies such as IgA nephropathy, technical issues associated with whole-exome sequencing and difficulties in identifying and computationally assessing non-canonical splicing variants, including deep intronic and synonymous changes. Candidate splicing variants might be identified using whole-exome, whole-genome or long-read sequencing, prioritized bioinformatically, and validated with targeted RNA sequencing or splicing assays. People with suspected Alport syndrome but no identified disease-causing variant should be managed as for Alport syndrome while awaiting confirmation of their diagnosis. Missing disease-causing variants are also common in other genetic kidney diseases, and the methods used for their resolution are the same. Our current inability to detect all disease-causing variants means that the contribution of genetic disease is underestimated for kidney phenotypes. Here, the authors discuss explanations for missing disease-causing variants in Alport syndrome, how clinicians and laboratories might manage missing variants and how to care for patients when a clinical suspicion of Alport syndrome exists but no disease-causing variant has been identified.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 7","pages":"499-511"},"PeriodicalIF":46.7,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393768","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}

引用次数: 0

Bridging structure and function: artificial intelligence-based modelling of kidney proteins 桥接结构和功能：基于人工智能的肾脏蛋白质建模。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-04 DOI: 10.1038/s41581-026-01060-6

Sean Wu, Weiguang Wang, Z. Hong Zhou, Fabien Scalzo, Ira Kurtz

{"title":"Bridging structure and function: artificial intelligence-based modelling of kidney proteins","authors":"Sean Wu, Weiguang Wang, Z. Hong Zhou, Fabien Scalzo, Ira Kurtz","doi":"10.1038/s41581-026-01060-6","DOIUrl":"10.1038/s41581-026-01060-6","url":null,"abstract":"The ability to predict the three-dimensional structure of a protein from its amino acid sequence has potential to provide insights into its function, and in the context of disease, its pathogenic mechanisms and potential drug targets. Artificial intelligence (AI)-driven algorithms, particularly AlphaFold and RoseTTAFold, have revolutionized the field of protein modelling, enabling rapid, high-confidence predictions of protein structures. In nephrology, these advances have clarified the molecular architecture of key renal systems such as podocyte slit diaphragm complexes, the conformational states of membrane transporters and the structural basis of channelopathies that affect polycystin channels. These developments have also enabled low-resolution modelling of complex macromolecular structures, providing insights into structural changes that might underlie the pathogenesis of disease mutants, and enabled virtual screening of drugs and toxins. Although these AI models have yielded important new insights, their integration with experimental methods, particularly cellular cryogenic electron tomography, remains crucial for capturing the domain flexibility, conformational dynamics and binding specificity of proteins in their native environment. Combining AI-based structure prediction with experimental validation will uncover novel pathophysiological mechanisms, guide drug discovery and reveal potential new avenues to target mechanisms of kidney disease. Advances in artificial intelligence-driven algorithms and experimental technologies have revolutionized the field of protein modelling. This Review describes how these developments have provided unprecedented insights into the structure of key proteins within the kidney, improved understanding of the relationships between protein structure and stability, and enabled mechanistic interpretation of variants that underlie a variety of kidney pathologies.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 6","pages":"385-405"},"PeriodicalIF":39.8,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350357","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}

引用次数: 0

The impact of social determinants of health on acute kidney injury 健康的社会决定因素对急性肾损伤的影响。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-04 DOI: 10.1038/s41581-026-01063-3

Samira Bell, Rolando Claure-Del Granado, Nuttha Lumlertgul, Mignon McCulloch, Amira Mohamed, Neesh Pannu, Manisha Sahay, Danielle E. Soranno, Marlies Ostermann, Ravindra Mehta, Shina Menon, on behalf of the 33rd ADQI expert panel

{"title":"The impact of social determinants of health on acute kidney injury","authors":"Samira Bell, Rolando Claure-Del Granado, Nuttha Lumlertgul, Mignon McCulloch, Amira Mohamed, Neesh Pannu, Manisha Sahay, Danielle E. Soranno, Marlies Ostermann, Ravindra Mehta, Shina Menon, on behalf of the 33rd ADQI expert panel","doi":"10.1038/s41581-026-01063-3","DOIUrl":"10.1038/s41581-026-01063-3","url":null,"abstract":"Acute kidney injury (AKI) is a common condition globally associated with substantial morbidity, mortality and costs to health-care systems. The epidemiology and outcomes of AKI differ within and between countries, and depend on multiple factors. Social determinants of health (SDoHs) are the circumstances in which people are born, grow, work, live and age, including the broader set of forces and systems that influence the conditions of everyday life. Despite advances in medical care, many inequities, including those associated with socioeconomic status, race, ethnicity, gender and environment, persist and are increasingly recognized to influence health outcomes. Superimposed on these inequities are differences in access to health care and health resources, including public health prevention, access to screening, early diagnosis and treatment (including kidney replacement therapy), and quality of care, which vary within and between high- and low-resource settings. Over the past few years, these disparities have intensified as societies have emerged from a global pandemic and are challenged with accelerating climate change and escalating levels of global conflict. However, the role of SDoHs remains poorly defined for people with or at risk of AKI. Targeted policies addressing SDoHs are essential to reduce AKI burden globally. Here, we examine the effects of SDoHs on the incidence, recognition, management, follow-up and outcomes of adult and paediatric populations at risk of or with AKI. Social determinants of health can have a considerable impact on patient outcomes. Here, the authors examine how social determinants of health contribute to the growing global burden of acute kidney injury and its inequities, and discuss key strategies for tackling disparities in acute kidney injury care and outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 6","pages":"438-452"},"PeriodicalIF":39.8,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350356","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}

引用次数: 0

Hepatokine regulation of kidney fibrosis 肝因子对肾纤维化的调节。

IF 39.8 1区医学

Nature Reviews Nephrology Pub Date : 2026-03-02 DOI: 10.1038/s41581-026-01065-1

Susan J. Allison

引用次数: 0