Nature Reviews Nephrology最新文献_第2页

Nephrogenomics, precision medicine and the role of genetic testing in adult kidney disease management 肾基因组学、精准医学和基因检测在成人肾脏疾病管理中的作用

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-06-16 DOI: 10.1038/s41581-025-00970-1

Ilias Bensouna, Alice Doreille, Marine Dancer, Anne-Sophie Lebre, Thomas Robert, Laurent Mesnard

{"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":"https://doi.org/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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"3 1","pages":""},"PeriodicalIF":41.5,"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}

引用次数: 0

Sepsis criteria and kidney function: eliminating sex, age and economic status biases 脓毒症标准和肾功能：消除性别、年龄和经济地位的偏见

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-06-12 DOI: 10.1038/s41581-025-00973-y

Ayse Akcan Arikan, Marlies Ostermann, Stuart L. Goldstein, John A. Kellum

{"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":"https://doi.org/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.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"5 1","pages":""},"PeriodicalIF":41.5,"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}

引用次数: 0

Improving nephrology care for people with cognitive impairments and their caregivers 改善认知障碍患者及其照护者的肾病护理

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-06-09 DOI: 10.1038/s41581-025-00976-9

Laura N. Gitlin, Nancy A. Hodgson

引用次数: 0

Incorporating dementia screening in the care of patients with kidney disease 将痴呆筛查纳入肾脏疾病患者的护理

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-06-06 DOI: 10.1038/s41581-025-00974-x

Dawn F. Wolfgram

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IL-6 signalling contributes to the pathogenesis of uraemic calciphylaxis IL-6信号参与尿毒性钙化反应的发病机制

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-06-04 DOI: 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":"https://doi.org/10.1038/s41581-025-00975-w","url":null,"abstract":"Uraemic calciphylaxis is a rare disease characterized by subcutaneous vessel thrombosis and ulcerative skin necrosis that predominantly affects patients with kidney failure. The disease results in substantial morbidity and mortality, but the pathogenesis is unclear and no curative therapies are available. Now, a new study reports a pathogenic role of IL-6–tissue factor (TF) signalling in uraemic calciphylaxis.The researchers hypothesised that a combination of systemic factors and local skin microenvironment changes trigger thrombosis and ischaemic necrosis. They found that sera from patients with uraemic calciphylaxis stimulated IL-6 signalling in human dermal microvascular endothelial cells. Furthermore, spatial transcriptomics analysis of skin biopsy samples from patients with uraemic calciphylaxis showed upregulation of genes with roles in IL-6 signalling (IL6, STAT3 and JAK1) and thrombosis (FN1) in vessels, and genes with roles in thrombosis (FN1, PLAU) and calcium homeostasis (SPP1, RUNX), as well as VEGFA, in adipose tissue. TYMP, which encodes thymidine phosphorylase, was upregulated in vessels, glands and adipose tissue. In addition, IL-6 ligand–receptor interactions between vessels, adipose tissue and glands were increased in skin samples from patients with uraemic calciphylaxis compared with skin samples from patients with kidney failure who did not have calciphylaxis. The major senders and recipients of IL-6 signalling were the microvessels.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"43 1","pages":""},"PeriodicalIF":41.5,"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}

引用次数: 0

Engineered CAR macrophages target kidney inflammation 工程化CAR巨噬细胞靶向肾脏炎症

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-27 DOI: 10.1038/s41581-025-00972-z

Susan J. Allison

{"title":"Engineered CAR macrophages target kidney inflammation","authors":"Susan J. Allison","doi":"10.1038/s41581-025-00972-z","DOIUrl":"https://doi.org/10.1038/s41581-025-00972-z","url":null,"abstract":"The administration of anti-inflammatory macrophages has been proposed as an approach to reduce tissue injury in response to inflammation; however, this approach is limited by the instability of macrophages and their potential to switch to a pro-inflammatory phenotype. To overcome these limitations, researchers have now developed a chimeric antigen receptor (CAR) macrophage (CAR-M) that demonstrates anti-inflammatory functions in response to a pro-inflammatory stimulus. “Our approach demonstrates the potential to improve the therapeutic efficacy of immune cells while maintaining a stable and desired phenotype within the inflammatory microenvironment,” states lead author, Qi Cao.Cao and colleagues engineered their CAR construct with an extracellular, anti-TNF single-chain fragment variable (scFv) linked to the intracellular domain of IL-4Rα, such that binding of the anti-TNF scFv to TNF triggered a signal switch to initiate an anti-inflammatory response. “A key innovation of our CAR methodology is the development of a novel chimeric signalling switch receptor (CSSR), which is designed to harness pro-inflammatory signals to drive an anti-inflammatory phenotype within the therapeutic cell,” explains Cao. “Our CSSR approach fundamentally differs from traditional CARs in two critical ways. First, conventional CARs typically augment the existing function of a cell, whereas our CSSR actively switches the cell’s functional output. Secondly, conventional CARs are predominantly used to enhance immune responses, whereas our CSSR is specifically designed to suppress them.”","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"35 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153529","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

Chronic kidney disease and dementia: an epidemiological perspective 慢性肾脏疾病和痴呆：流行病学观点

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-22 DOI: 10.1038/s41581-025-00967-w

M. Arfan Ikram

{"title":"Chronic kidney disease and dementia: an epidemiological perspective","authors":"M. Arfan Ikram","doi":"10.1038/s41581-025-00967-w","DOIUrl":"https://doi.org/10.1038/s41581-025-00967-w","url":null,"abstract":"Ageing populations worldwide face increasing challenges of multimorbidity (that is, the co-occurrence of two or more chronic conditions). The combination of chronic kidney disease (CKD) and dementia occurs more frequently than it would by simple coincidence, owing to several underlying biological and clinical mechanisms. Population-based cohort studies are an important epidemiological tool and have contributed to improved understanding of these mechanisms. These mechanisms include uniquely shared haemodynamic features of vasculature, overlapping risk factor profiles, and direct neurotoxic effects of accumulating waste products due to poor kidney function. The effect of these pathways is suggested to differ across gender, relevant demographic subgroups, and populations from low- to middle-income countries. Yet, given their study design, population-based cohort studies also inherently face several methodological challenges. These challenges pertain to the use of biomarkers that do not always fully capture the structure and function of the kidney or the brain; bidirectionality across the pathways under study; and practical issues of proper causal inference in light of incomplete distinction between confounders, mediators and effect modifiers. This Review describes our current understanding of the link between CKD and dementia, with a focus on knowledge synthesized from population-based cohort studies. Methodological challenges and possible solutions will be described and directions for future research areas will be outlined.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"92 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113643","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 intelligent podocyte: sensing and responding to a complex microenvironment 智能足细胞：感知和响应复杂的微环境

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-08 DOI: 10.1038/s41581-025-00965-y

John F. Bertram, Luise A. Cullen-McEwen, Vinicius Andrade-Oliveira, Niels Olsen Saraiva Câmara

{"title":"The intelligent podocyte: sensing and responding to a complex microenvironment","authors":"John F. Bertram, Luise A. Cullen-McEwen, Vinicius Andrade-Oliveira, Niels Olsen Saraiva Câmara","doi":"10.1038/s41581-025-00965-y","DOIUrl":"https://doi.org/10.1038/s41581-025-00965-y","url":null,"abstract":"Podocytes are key components of the glomerular filtration barrier — a specialized structure that is responsible for the filtration of blood by the kidneys. They therefore exist in a unique microenvironment exposed to mechanical force and the myriad molecules that cross the filtration barrier. To survive and thrive, podocytes must continually sense and respond to their ever-changing microenvironment. Sensing is achieved by interactions with the surrounding extracellular matrix and neighbouring cells, through a variety of pathways, to sense changes in environmental factors such as nutrient levels including glucose and lipids, oxygen levels, pH and pressure. The response mechanisms similarly involve a range of processes, including signalling pathways and the actions of specific organelles that initiate and regulate appropriate responses, including alterations in cell metabolism, immune regulation and changes in podocyte structure and cognate functions. These functions ultimately affect glomerular and kidney health. Imbalances in these processes can lead to inflammation, podocyte loss and glomerular disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"56 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920372","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 effects of sex hormone therapy on kidney function 性激素治疗对肾功能的影响

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-06 DOI: 10.1038/s41581-025-00966-x

Ellen F. Carney

{"title":"The effects of sex hormone therapy on kidney function","authors":"Ellen F. Carney","doi":"10.1038/s41581-025-00966-x","DOIUrl":"https://doi.org/10.1038/s41581-025-00966-x","url":null,"abstract":"Progression of chronic kidney disease (CKD) is generally faster in cisgender men than cisgender women, suggesting a protective effect of female sex. An observational study in 44 transgender individuals who initiated either feminizing (estradiol and antiandrogens) or masculinizing (testosterone) hormone therapy provides new insights into the effects of sex hormones on the kidney. “This population provides a unique opportunity to study the effects of well-defined changes in sex hormone concentrations,” says researcher Sarah van Eeghen.Sex hormone therapy also resulted in changes in the concentrations of tubular injury biomarkers, with decreases in urinary NGAL, MCP1 and YKL-40 with feminizing therapy and increases in urinary YKL-40 and plasma TNFR1 with masculinizing therapy. “These results suggest that estradiol may protect against early tubular injury and inflammation, whereas testosterone may promote kidney inflammation,” comments van Eeghen. In addition, a plasma proteomics analysis identified several circulating proteins with kidney-protective properties that increased during feminizing therapy and/or decreased during masculinizing therapy. Many of these proteins were positively associated with estradiol and negatively associated with testosterone, including proteins with roles in endothelial function, modulation of inflammation and preservation of kidney structural integrity.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909974","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

Implantable bioelectronics and wearable sensors for kidney health and disease 用于肾脏健康和疾病的植入式生物电子学和可穿戴传感器

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-29 DOI: 10.1038/s41581-025-00961-2

Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers

{"title":"Implantable bioelectronics and wearable sensors for kidney health and disease","authors":"Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers","doi":"10.1038/s41581-025-00961-2","DOIUrl":"https://doi.org/10.1038/s41581-025-00961-2","url":null,"abstract":"Established clinical practices for monitoring kidney health and disease — including biopsy and serum biomarker analysis — suffer from practical limitations in monitoring frequency and lack adequate sensitivity for early disease detection. Engineering advances in biosensors have led to the development of wearable and implantable systems for monitoring of kidney health. Non-invasive microfluidic systems have demonstrated utility in the detection of kidney-relevant biomarkers, such as creatinine, urea and electrolytes in peripheral body fluids such as sweat, interstitial fluid, tears and saliva. Implantable systems may aid the identification of early transplant rejection through analysis of organ temperature and perfusion, and enable real-time assessment of inflammation through the use of thermal sensors. These technologies enable continuous, real-time monitoring of kidney health, offering complementary information to standard clinical procedures to alert physicians of changes in kidney health for early intervention. In this Review, we explore devices for monitoring renal biomarkers in peripheral biofluids and discuss developments in implantable sensors for the direct measurement of the local, biophysical properties of kidney tissue. We also describe potential clinical applications, including monitoring of chronic kidney disease, acute kidney injury and allograft health.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889436","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