Pub Date : 2025-06-27DOI: 10.1038/s41581-025-00986-7
Ellen F. Carney
{"title":"Superior efficacy of empagliflozin and finerenone combination therapy versus monotherapy in patients with CKD and T2DM","authors":"Ellen F. Carney","doi":"10.1038/s41581-025-00986-7","DOIUrl":"10.1038/s41581-025-00986-7","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 8","pages":"523-523"},"PeriodicalIF":39.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500584","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}
Pub Date : 2025-06-23DOI: 10.1038/s41581-025-00981-y
Susan J. Allison
{"title":"Harnessing plant thylakoids to restore cellular function in AKI","authors":"Susan J. Allison","doi":"10.1038/s41581-025-00981-y","DOIUrl":"10.1038/s41581-025-00981-y","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 8","pages":"523-523"},"PeriodicalIF":39.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341228","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}
Pub Date : 2025-06-19DOI: 10.1038/s41581-025-00968-9
Julio Saez-Rodriguez
The transition from data scientist to patient–scientist has given me new perspectives into clinical research and strengthened my commitment to open science. Although limitations on data availability have led to frustration, collaboration bodes well for a future in which patients will have access to more personalized information.
{"title":"Leveraging data as a patient–scientist: frustrations and opportunities","authors":"Julio Saez-Rodriguez","doi":"10.1038/s41581-025-00968-9","DOIUrl":"10.1038/s41581-025-00968-9","url":null,"abstract":"The transition from data scientist to patient–scientist has given me new perspectives into clinical research and strengthened my commitment to open science. Although limitations on data availability have led to frustration, collaboration bodes well for a future in which patients will have access to more personalized information.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 9","pages":"577-577"},"PeriodicalIF":39.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41581-025-00968-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319712","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}
Microplastics and nanoplastics are ubiquitous environmental pollutants that contaminate air, food and water supplies, resulting in widespread human exposure and potential health risks. Varying concentrations of particulate plastics have been identified in human tissues and body fluids, including the heart, kidney, liver, brain, blood and urine. Studies in animal models and human cells have reported that particulate plastics can induce oxidative stress, cell death and inflammation as well as disrupt metabolism and immune function. They have also been shown to have toxic effects on kidney and cardiovascular cells, which are exacerbated by the presence of other environmental contaminants such as heavy metals. Patients with kidney failure might be at risk of increased exposure to particulate plastics during dialysis. Furthermore, clinical evidence suggests that particulate plastic exposure is a risk factor for cardiovascular disease. Approaches to mitigating such exposure include degradation via abiotic and biotic processes, improved waste management and water filtration approaches and use of alternative materials. Further research into the fate, toxicity and health consequences of particulate plastics is imperative to inform strategies to address this escalating environmental and health concern. The impact of exposure to particulate plastics on human health is a topic of increasing concern. Here, the authors discuss routes of exposure to microparticles and nanoparticles and potential mechanisms of toxicity in the kidney and cardiovascular systems.
{"title":"Effects of microplastics and nanoplastics on the kidney and cardiovascular system","authors":"Yu-Hsuan Lee, Cai-Mei Zheng, Ying-Jan Wang, Yung-Li Wang, Hui-Wen Chiu","doi":"10.1038/s41581-025-00971-0","DOIUrl":"10.1038/s41581-025-00971-0","url":null,"abstract":"Microplastics and nanoplastics are ubiquitous environmental pollutants that contaminate air, food and water supplies, resulting in widespread human exposure and potential health risks. Varying concentrations of particulate plastics have been identified in human tissues and body fluids, including the heart, kidney, liver, brain, blood and urine. Studies in animal models and human cells have reported that particulate plastics can induce oxidative stress, cell death and inflammation as well as disrupt metabolism and immune function. They have also been shown to have toxic effects on kidney and cardiovascular cells, which are exacerbated by the presence of other environmental contaminants such as heavy metals. Patients with kidney failure might be at risk of increased exposure to particulate plastics during dialysis. Furthermore, clinical evidence suggests that particulate plastic exposure is a risk factor for cardiovascular disease. Approaches to mitigating such exposure include degradation via abiotic and biotic processes, improved waste management and water filtration approaches and use of alternative materials. Further research into the fate, toxicity and health consequences of particulate plastics is imperative to inform strategies to address this escalating environmental and health concern. The impact of exposure to particulate plastics on human health is a topic of increasing concern. Here, the authors discuss routes of exposure to microparticles and nanoparticles and potential mechanisms of toxicity in the kidney and cardiovascular systems.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 9","pages":"585-596"},"PeriodicalIF":39.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319630","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}
Fibroblasts are a special type of interstitial cell that has an essential role in maintaining the structural framework of tissues and organs. In response to injury, fibroblasts are activated and produce large amounts of extracellular matrix proteins. Fibroblast activation has a crucial role in tissue repair and wound healing. However, uncontrolled and persistent activation of fibroblasts ultimately leads to fibrotic diseases of organs such as the kidney, liver, lung and heart. Activated fibroblasts predominantly originate from the local activation and expansion of resident fibroblasts and pericytes. A diverse array of extracellular cues, including soluble factors, extracellular vesicles, matricellular proteins and mechanical stiffness, induce fibroblast activation after tissue injury. Fibroblast activation primarily takes place in the fibrogenic niche, a unique tissue microenvironment in which fibroblasts interact with injured parenchymal cells, inflammatory cells and endothelial cells. The fates of activated fibroblasts, including apoptosis, senescence, dedifferentiation and lineage reprogramming, determine the outcome of tissue repair and organ fibrosis. Potential therapeutic strategies for fibrotic diseases include disrupting the formation of the fibrogenic niche, inhibiting fibroblast activation, promoting fibroblast depletion, accelerating fibrosis resolution or promoting tissue repair and regeneration. Here, the authors discuss the heterogeneity and origins of fibroblasts in various organs, the mediators that induce fibroblast activation and fibroblast trajectory and fate. They also highlight potential approaches to targeting fibroblasts as a therapeutic strategy for chronic fibrotic diseases.
{"title":"Fibroblast activation and heterogeneity in fibrotic disease","authors":"Xiaoyao Zhang \u0000 (, ), Yuxi Zhang \u0000 (, ), Youhua Liu \u0000 (, )","doi":"10.1038/s41581-025-00969-8","DOIUrl":"10.1038/s41581-025-00969-8","url":null,"abstract":"Fibroblasts are a special type of interstitial cell that has an essential role in maintaining the structural framework of tissues and organs. In response to injury, fibroblasts are activated and produce large amounts of extracellular matrix proteins. Fibroblast activation has a crucial role in tissue repair and wound healing. However, uncontrolled and persistent activation of fibroblasts ultimately leads to fibrotic diseases of organs such as the kidney, liver, lung and heart. Activated fibroblasts predominantly originate from the local activation and expansion of resident fibroblasts and pericytes. A diverse array of extracellular cues, including soluble factors, extracellular vesicles, matricellular proteins and mechanical stiffness, induce fibroblast activation after tissue injury. Fibroblast activation primarily takes place in the fibrogenic niche, a unique tissue microenvironment in which fibroblasts interact with injured parenchymal cells, inflammatory cells and endothelial cells. The fates of activated fibroblasts, including apoptosis, senescence, dedifferentiation and lineage reprogramming, determine the outcome of tissue repair and organ fibrosis. Potential therapeutic strategies for fibrotic diseases include disrupting the formation of the fibrogenic niche, inhibiting fibroblast activation, promoting fibroblast depletion, accelerating fibrosis resolution or promoting tissue repair and regeneration. Here, the authors discuss the heterogeneity and origins of fibroblasts in various organs, the mediators that induce fibroblast activation and fibroblast trajectory and fate. They also highlight potential approaches to targeting fibroblasts as a therapeutic strategy for chronic fibrotic diseases.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 9","pages":"613-632"},"PeriodicalIF":39.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319714","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}
Pub Date : 2025-06-16DOI: 10.1038/s41581-025-00970-1
Ilias Bensouna, Alice Doreille, Marine Dancer, Anne-Sophie Lebre, Thomas Robert, Laurent Mesnard
Genetic investigations in nephrology have long been viewed as the prerogative of paediatricians or restricted to archetypal genetic nephropathies with highly penetrant variants affecting young adults. However, genetic testing has emerged as a pivotal tool in the field of adult nephrology, with the ability to revolutionize the understanding and management of adult kidney diseases. Here, we explore the multifaceted role of genomic testing (such as exome or genome sequencing) in chronic kidney disease, shedding light on current genetic findings for reframing diagnostic paradigms and tailoring treatment strategies. Genomic testing has enhanced our comprehension of kidney diseases of unknown origin by showing that ~20% are attributable to kidney Mendelian genetic disorders with as yet unsuspected phenocopies. Beyond genetic counselling, genetic integration can optimize therapeutic interventions, kidney transplantation and kidney disease prevention, both in index cases and in at-risk family members. Furthermore, the emerging field of rapid nephrogenomics promises streamlined diagnosis and management, with a potential impact on early therapeutic strategy. Importantly, although costs continue to decrease, the integration of genomic technologies in nephrology practice raises several ethical concerns, especially regarding variants of uncertain significance, and incidental or secondary findings. Establishing multidisciplinary frameworks should maximize the potential of nephrogenomics to improve patient outcomes. This Review examines the use of pangenomic analysis to improve molecular diagnoses in adult nephrology, including available sequencing methods and their applications. The authors also discuss current barriers to translating genetic information into actionable diagnoses, ethical challenges and the key role of multidisciplinary collaboration.
{"title":"Nephrogenomics, precision medicine and the role of genetic testing in adult kidney disease management","authors":"Ilias Bensouna, Alice Doreille, Marine Dancer, Anne-Sophie Lebre, Thomas Robert, Laurent Mesnard","doi":"10.1038/s41581-025-00970-1","DOIUrl":"10.1038/s41581-025-00970-1","url":null,"abstract":"Genetic investigations in nephrology have long been viewed as the prerogative of paediatricians or restricted to archetypal genetic nephropathies with highly penetrant variants affecting young adults. However, genetic testing has emerged as a pivotal tool in the field of adult nephrology, with the ability to revolutionize the understanding and management of adult kidney diseases. Here, we explore the multifaceted role of genomic testing (such as exome or genome sequencing) in chronic kidney disease, shedding light on current genetic findings for reframing diagnostic paradigms and tailoring treatment strategies. Genomic testing has enhanced our comprehension of kidney diseases of unknown origin by showing that ~20% are attributable to kidney Mendelian genetic disorders with as yet unsuspected phenocopies. Beyond genetic counselling, genetic integration can optimize therapeutic interventions, kidney transplantation and kidney disease prevention, both in index cases and in at-risk family members. Furthermore, the emerging field of rapid nephrogenomics promises streamlined diagnosis and management, with a potential impact on early therapeutic strategy. Importantly, although costs continue to decrease, the integration of genomic technologies in nephrology practice raises several ethical concerns, especially regarding variants of uncertain significance, and incidental or secondary findings. Establishing multidisciplinary frameworks should maximize the potential of nephrogenomics to improve patient outcomes. This Review examines the use of pangenomic analysis to improve molecular diagnoses in adult nephrology, including available sequencing methods and their applications. The authors also discuss current barriers to translating genetic information into actionable diagnoses, ethical challenges and the key role of multidisciplinary collaboration.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 9","pages":"597-612"},"PeriodicalIF":39.8,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296007","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}
Pub Date : 2025-06-12DOI: 10.1038/s41581-025-00973-y
Ayse Akcan Arikan, Marlies Ostermann, Stuart L. Goldstein, John A. Kellum
The kidney is a target organ for the dysregulated host response to infection that defines sepsis, and acute kidney injury (AKI) is often an early manifestation of this response. Current sepsis criteria for adults (Sepsis-3) continue to include outmoded measures of kidney health, such as absolute creatinine values, which are used in organ failure scoring independently of baseline kidney function or treatment with dialysis. This approach perpetuates disparities, as older female patients require much larger decreases in kidney function compared with young male patients to achieve the same ‘renal domain’ points, exacerbating sex- and age-based inequities in health assessment and response. Furthermore, the latest data-driven machine learning-assisted paediatric sepsis criteria (the Phoenix Sepsis Score) have excluded kidney function entirely from sepsis diagnosis. Consequently, these criteria will exclude a child with pneumonia and associated AKI, even if receiving dialysis, from a sepsis diagnosis unless other organs fail. This inconsistency, given the extensive refinement and validation of AKI diagnostic criteria over the past three decades, is unacceptable. Current criteria for diagnosis of sepsis in both adults and children fail to incorporate crucial advances in the diagnosis of kidney disease. We maintain that it is imperative that kidney injury is quantified accurately in sepsis scoring systems free of sex, race and other biases. In this Perspective article, the authors argue that current criteria for sepsis in adults and children fail to adequately consider one of the most common sepsis-related organ dysfunctions, acute kidney injury, which has important implications for diagnosis and patient outcomes.
{"title":"Sepsis criteria and kidney function: eliminating sex, age and economic status biases","authors":"Ayse Akcan Arikan, Marlies Ostermann, Stuart L. Goldstein, John A. Kellum","doi":"10.1038/s41581-025-00973-y","DOIUrl":"10.1038/s41581-025-00973-y","url":null,"abstract":"The kidney is a target organ for the dysregulated host response to infection that defines sepsis, and acute kidney injury (AKI) is often an early manifestation of this response. Current sepsis criteria for adults (Sepsis-3) continue to include outmoded measures of kidney health, such as absolute creatinine values, which are used in organ failure scoring independently of baseline kidney function or treatment with dialysis. This approach perpetuates disparities, as older female patients require much larger decreases in kidney function compared with young male patients to achieve the same ‘renal domain’ points, exacerbating sex- and age-based inequities in health assessment and response. Furthermore, the latest data-driven machine learning-assisted paediatric sepsis criteria (the Phoenix Sepsis Score) have excluded kidney function entirely from sepsis diagnosis. Consequently, these criteria will exclude a child with pneumonia and associated AKI, even if receiving dialysis, from a sepsis diagnosis unless other organs fail. This inconsistency, given the extensive refinement and validation of AKI diagnostic criteria over the past three decades, is unacceptable. Current criteria for diagnosis of sepsis in both adults and children fail to incorporate crucial advances in the diagnosis of kidney disease. We maintain that it is imperative that kidney injury is quantified accurately in sepsis scoring systems free of sex, race and other biases. In this Perspective article, the authors argue that current criteria for sepsis in adults and children fail to adequately consider one of the most common sepsis-related organ dysfunctions, acute kidney injury, which has important implications for diagnosis and patient outcomes.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 8","pages":"565-575"},"PeriodicalIF":39.8,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268540","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}
Pub Date : 2025-06-09DOI: 10.1038/s41581-025-00976-9
Laura N. Gitlin, Nancy A. Hodgson
People with chronic kidney disease and cognitive impairment are at an increased risk of adverse health outcomes, and these intersecting comorbidities are increasing in prevalence worldwide. Innovative care models that involve a cognitive-aware lens and consider the needs of family caregivers are needed to provide quality care to patients.
{"title":"Improving nephrology care for people with cognitive impairments and their caregivers","authors":"Laura N. Gitlin, Nancy A. Hodgson","doi":"10.1038/s41581-025-00976-9","DOIUrl":"10.1038/s41581-025-00976-9","url":null,"abstract":"People with chronic kidney disease and cognitive impairment are at an increased risk of adverse health outcomes, and these intersecting comorbidities are increasing in prevalence worldwide. Innovative care models that involve a cognitive-aware lens and consider the needs of family caregivers are needed to provide quality care to patients.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 8","pages":"520-521"},"PeriodicalIF":39.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237905","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}
Pub Date : 2025-06-06DOI: 10.1038/s41581-025-00974-x
Dawn F. Wolfgram
Prevalence of cognitive impairment and dementia in people with kidney disease is disproportionately high, and improved detection is needed. Implementing routine screening for dementia in people receiving dialysis, who are at high risk of cognitive decline, would facilitate diagnosis and enable patients to receive appropriate therapeutics and support.
{"title":"Incorporating dementia screening in the care of patients with kidney disease","authors":"Dawn F. Wolfgram","doi":"10.1038/s41581-025-00974-x","DOIUrl":"10.1038/s41581-025-00974-x","url":null,"abstract":"Prevalence of cognitive impairment and dementia in people with kidney disease is disproportionately high, and improved detection is needed. Implementing routine screening for dementia in people receiving dialysis, who are at high risk of cognitive decline, would facilitate diagnosis and enable patients to receive appropriate therapeutics and support.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 8","pages":"518-519"},"PeriodicalIF":39.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228677","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}
Pub Date : 2025-06-04DOI: 10.1038/s41581-025-00975-w
Ellen F. Carney
{"title":"IL-6 signalling contributes to the pathogenesis of uraemic calciphylaxis","authors":"Ellen F. Carney","doi":"10.1038/s41581-025-00975-w","DOIUrl":"10.1038/s41581-025-00975-w","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 7","pages":"436-436"},"PeriodicalIF":39.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211260","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}
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