Nature Reviews Nephrology最新文献_第2页

Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder. 心血管-肾-代谢综合征作为线粒体系统疾病。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-24 DOI: 10.1038/s41581-026-01127-4

Shen Li, E Dale Abel, Zoltan Arany, Joseph A Baur, Liming Pei, Katalin Susztak

{"title":"Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.","authors":"Shen Li, E Dale Abel, Zoltan Arany, Joseph A Baur, Liming Pei, Katalin Susztak","doi":"10.1038/s41581-026-01127-4","DOIUrl":"https://doi.org/10.1038/s41581-026-01127-4","url":null,"abstract":"Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem disorder in which obesity, diabetes, chronic kidney disease, and cardiovascular disease reinforce one another through shared pathobiological characteristics and bidirectional organ crosstalk. Rather than representing the mere coexistence of diseases, CKM syndrome can be understood as a mitochondrial systems disorder. In energy-intensive tissues such as the myocardium and renal tubules, chronic haemodynamic stress, substrate excess, hypoxia and neurohormonal activation converge on mitochondrial programmes governing oxidative phosphorylation, redox balance, organelle dynamics and quality control. Disruption of these programmes, including impaired fatty acid oxidation, suppressed biogenesis, defective mitophagy and mitochondrial DNA instability, reduces bioenergetic reserve and promotes reactive oxygen species generation, inflammatory signalling and progressive organ dysfunction. Mitochondrial dysfunction in other metabolic tissues further amplifies these processes. In the liver, reduced fatty acid oxidation promotes steatosis, insulin resistance and the release of lipids, whereas in skeletal muscle and adipose tissue, impaired oxidative capacity and insulin resistance increases lipid spillover and systemic inflammation. Mitochondria-derived signals - including FGF21, GDF15, succinate and circulating mitochondrial DNA - enable bidirectional communication between organs, reinforcing multi-organ decline in a positive-feedback loop. Advancing our understanding of mitochondrial dysfunction and inter-organ communication may provide new mechanistic insights into CKM syndrome progression and inform the development of mitochondria-targeted therapeutic strategies.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":46.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040075","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 role of senescence in kidney ageing, injury and fibrosis 衰老在肾脏老化、损伤和纤维化中的作用

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-23 DOI: 10.1038/s41581-026-01123-8

Piotr P. Janas,Tilly Mason,David A. Ferenbach

引用次数: 0

Enhanced urea uptake promotes bleeding in advanced CKD 尿素摄取增强促进晚期CKD出血

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-22 DOI: 10.1038/s41581-026-01134-5

Monica Wang

引用次数: 0

Primary cilia: master conductors of cellular communication in development and disease. 初级纤毛：发育和疾病中细胞通讯的主要导体。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-21 DOI: 10.1038/s41581-026-01129-2

Oskar K Thomsen, Gaia Pigino, Lotte B Pedersen, Gregory J Pazour, Dagmar Wachten, Søren T Christensen

{"title":"Primary cilia: master conductors of cellular communication in development and disease.","authors":"Oskar K Thomsen, Gaia Pigino, Lotte B Pedersen, Gregory J Pazour, Dagmar Wachten, Søren T Christensen","doi":"10.1038/s41581-026-01129-2","DOIUrl":"https://doi.org/10.1038/s41581-026-01129-2","url":null,"abstract":"Primary cilia are microtubule-based organelles that function as cellular antennae, integrating diverse signalling pathways essential for tissue development and function. Dysregulation of ciliary signalling is linked to a broad spectrum of disorders known as ciliopathies, which affect most tissues and organs in the body. Primary cilia are dynamic hubs in which selective trafficking and compartmentalization of receptors, effectors and second messengers shape the strength, duration and specificity of cellular responses. Intraflagellar transport, ciliary gating and cargo adaptors establish and dynamically remodel ciliary composition, enabling signalling through Hedgehog, G-protein-coupled receptors, transient receptor potential proteins, receptor tyrosine kinases and the TGFβ superfamily to coordinate developmental patterning, cell proliferation and differentiation, metabolism and tissue homeostasis. Disruption of ciliary architecture, trafficking or signalling can therefore produce diverse and tissue-specific disease phenotypes, including polycystic kidney disease, retinal degeneration, skeletal abnormalities, cardiovascular diseases, neurodevelopmental disorders and obesity. Emerging evidence indicates that cell-type-specific and temporally dynamic ciliary signatures determine signalling competence and disease susceptibility. Defining these signatures and the mechanisms that regulate their plasticity could lead to new therapeutic opportunities for ciliopathies and other cilia-associated diseases.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":46.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017167","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

Ferroptosis in kidney disease. 肾病中的铁下垂。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-18 DOI: 10.1038/s41581-026-01131-8

Tianyi Wang, Shumin Sun, Andreas Linkermann, Junxia Min, Fudi Wang

{"title":"Ferroptosis in kidney disease.","authors":"Tianyi Wang, Shumin Sun, Andreas Linkermann, Junxia Min, Fudi Wang","doi":"10.1038/s41581-026-01131-8","DOIUrl":"https://doi.org/10.1038/s41581-026-01131-8","url":null,"abstract":"Kidney disease is a growing global public health concern that is associated with high rates of severe morbidity and mortality. Accumulating preclinical and clinical evidence suggests that ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, drives the pathogenesis and progression of diverse kidney disorders, including acute kidney injury, chronic kidney disease, renal cell carcinoma and autosomal-dominant polycystic kidney disease. Ferroptosis of renal tubular epithelial cells and intrarenal immune cells engages complex crosstalk with other regulated cell death pathways, amplifying responses and aggravating renal tissue damage. Several biomarkers of early kidney injury, such as the iron regulator NGAL and the phosphatidylserine-binding protein KIM1, are associated with features of ferroptotic cell death, suggesting their potential utility as indirect indicators of early ferroptotic lesions in the kidney. Furthermore, multimodal imaging platforms that integrate optical, magnetic resonance, photoacoustic and radionuclide techniques enable specific in vivo detection of ferroptotic hallmarks, facilitating early diagnosis of kidney lesions. Numerous preclinical studies have identified a diverse range of synthetic small-molecule agents, natural phytochemicals and metabolic modulators that are able to modify ferroptotic signalling. These agents have been shown to mitigate renal parenchymal injury or suppress the proliferation of malignant kidney cells, robustly establishing ferroptosis as a promising therapeutic target for kidney diseases.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":46.7,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002114","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

Megalin: from structure to function. meggalin：从结构到功能。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-18 DOI: 10.1038/s41581-026-01130-9

Elynna B Youm, Andrew Beenken, Ora A Weisz

{"title":"Megalin: from structure to function.","authors":"Elynna B Youm, Andrew Beenken, Ora A Weisz","doi":"10.1038/s41581-026-01130-9","DOIUrl":"https://doi.org/10.1038/s41581-026-01130-9","url":null,"abstract":"The proximal tubule maintains a robust endocytic pathway that is necessary for the recovery of proteins and vitamins from the ultrafiltrate and for the rapid regulation of ion transport. The large multiligand receptor megalin is essential to this process. In the absence of functional megalin, membrane and fluid flux through endocytic compartments is profoundly compromised, whereas the binding of filtered drugs to megalin is a major cause of nephrotoxicity. Insights into the structure of megalin offers clues as to how megalin might drive endocytic dynamics through pH-dependent conformational rearrangements, and findings from focused ion beam-scanning electron microscopy and machine learning-assisted segmentation challenge the traditional model of proximal tubule endocytosis and instead support a model in which a continuous network of dense apical tubules, together with the endoplasmic reticulum, regulates the control of ligand passage, fission and dissociation. In addition to its function as an endocytic receptor, megalin maintains proximal tubule function through other mechanisms. Genomic analyses and animal studies show that predicted alterations in megalin expression have complex effects on disease progression and protection. Consistent with these observations, megalin expression affects proximal tubule transcription and cell metabolism, with important consequences for disease pathology.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":46.7,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002130","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

Epidemiology, mechanisms and clinical implications of heat-related kidney disease. 热相关性肾病的流行病学、发病机制及临床意义。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-16 DOI: 10.1038/s41581-026-01126-5

Lucy McMullen, Alexandra Gallagher, Daniel Gagnon, Zachary J Schlader, Zoltan H Endre, Natasha M Rogers, Timothy English, Shuchi Anand, Jason Glaser, Vivekanand Jha, Meg J Jardine, Ollie Jay, Brendan Smyth

{"title":"Epidemiology, mechanisms and clinical implications of heat-related kidney disease.","authors":"Lucy McMullen, Alexandra Gallagher, Daniel Gagnon, Zachary J Schlader, Zoltan H Endre, Natasha M Rogers, Timothy English, Shuchi Anand, Jason Glaser, Vivekanand Jha, Meg J Jardine, Ollie Jay, Brendan Smyth","doi":"10.1038/s41581-026-01126-5","DOIUrl":"https://doi.org/10.1038/s41581-026-01126-5","url":null,"abstract":"Heat exposure is an emerging threat to kidney health, although the mechanisms and magnitude of the problem are incompletely understood. Epidemiological data consistently link hot temperatures with increased kidney morbidity, and heat-stress kidney injury is associated with chronic kidney disease (CKD) in some occupational and agricultural studies. However, the extent to which increasing ambient temperatures will contribute to greater incidence, prevalence and progression of CKD in broader populations is not well characterized. As global temperatures and heatwave frequency increase, people with existing CKD might face dual threats of acute morbidity during heat events and the possibility of accelerated decline in kidney function. Structural determinants, such as housing quality, occupational exposure and access to cooling, compound background physiological vulnerability due to age and comorbidities. Despite this risk, evidence guiding individualized mitigation of heat risk for people with CKD is extrapolated from what is known about how healthy volunteers respond to heat stress. Preventing the growing burden of heat-related kidney injury demands urgent climate action alongside a coordinated kidney health response, with global research collaboration and integration of clinical and societal strategies targeting patient education, context-specific clinical guidance and strong policy responses addressing health inequities and climate resilience.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":46.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983401","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

Uprooting inequity: cultivating a flourishing and socially accountable nephrologist workforce for Indigenous peoples 根除不平等：为土著人民培养一支繁荣和对社会负责的肾病专家队伍。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-15 DOI: 10.1038/s41581-026-01133-6

Jung G. Kim, Lilia Cervantes, Germaine Wong, Scott Jones, Curtis Walker, Dowin Boatright, David Tipene-Leach

引用次数: 0

City design for kidney health 肾脏健康的城市设计。

IF 46.7 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-14 DOI: 10.1038/s41581-026-01132-7

Pengfei Li (, ), Luxia Zhang (, )

引用次数: 0

Mechanisms of regeneration and maladaptive repair in acute kidney injury 急性肾损伤的再生和不适应修复机制

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2026-09-10 DOI: 10.1038/s41581-026-01115-8

Tobias Seibt,Konrad Hoeft,Gideon J. L. Schaefer,Adam Wahida,Razelle Kurzrock,Marcus Conrad,Rafael Kramann

引用次数: 0