Nature Reviews Nephrology最新文献_第5页

A guide to studying 3D genome structure and dynamics in the kidney 肾脏三维基因组结构和动态研究指南

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-10-15 DOI: 10.1038/s41581-024-00894-2

Brian J. Beliveau, Shreeram Akilesh

{"title":"A guide to studying 3D genome structure and dynamics in the kidney","authors":"Brian J. Beliveau, Shreeram Akilesh","doi":"10.1038/s41581-024-00894-2","DOIUrl":"10.1038/s41581-024-00894-2","url":null,"abstract":"The human genome is tightly packed into the 3D environment of the cell nucleus. Rapidly evolving and sophisticated methods of mapping 3D genome architecture have shed light on fundamental principles of genome organization and gene regulation. The genome is physically organized on different scales, from individual genes to entire chromosomes. Nuclear landmarks such as the nuclear envelope and nucleoli have important roles in compartmentalizing the genome within the nucleus. Genome activity (for example, gene transcription) is also functionally partitioned within this 3D organization. Rather than being static, the 3D organization of the genome is tightly regulated over various time scales. These dynamic changes in genome structure over time represent the fourth dimension of the genome. Innovative methods have been used to map the dynamic regulation of genome structure during important cellular processes including organism development, responses to stimuli, cell division and senescence. Furthermore, disruptions to the 4D genome have been linked to various diseases, including of the kidney. As tools and approaches to studying the 4D genome become more readily available, future studies that apply these methods to study kidney biology will provide insights into kidney function in health and disease. Here, the authors describe approaches to investigating 3D genome architecture and dynamics. They discuss the physical organization and dynamic regulation of the genome and highlight studies that have provided insights into the roles of genome structure and regulation in kidney health and disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 2","pages":"97-114"},"PeriodicalIF":28.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435976","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

Renal nerves in physiology, pathophysiology and interoception 生理、病理生理学和互感中的肾神经

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-10-03 DOI: 10.1038/s41581-024-00893-3

Louise C. Evans, Alex Dayton, John W. Osborn

{"title":"Renal nerves in physiology, pathophysiology and interoception","authors":"Louise C. Evans, Alex Dayton, John W. Osborn","doi":"10.1038/s41581-024-00893-3","DOIUrl":"10.1038/s41581-024-00893-3","url":null,"abstract":"Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure. Increased renal sympathetic nerve activity is thought to contribute to hypertension by promoting renal sodium retention, renin release and renal vasoconstriction. This hypothesis led to the development of catheter-based renal denervation (RDN) for the treatment of hypertension. Two RDN devices that ablate both efferent and afferent renal nerves received FDA approval for this indication in 2023. However, in animal models, selective ablation of afferent renal nerves resulted in comparable anti-hypertensive effects to ablation of efferent and afferent renal nerves and was associated with a reduction in sympathetic nerve activity. Selective afferent RDN also improved kidney function in a chronic kidney disease model. Notably, the beneficial effects of RDN extend beyond hypertension and chronic kidney disease to other clinical conditions that are associated with elevated sympathetic nerve activity, including heart failure and arrhythmia. These findings suggest that the kidney is an interoceptive organ, as increased renal sensory nerve activity modulates sympathetic activity to other organs. Future studies are needed to translate this knowledge into novel therapies for the treatment of hypertension and other cardiorenal diseases. Here, the authors discuss the roles of renal nerves and the effects of renal denervation in hypertension, chronic kidney disease, heart failure and arrhythmias. They suggest that interruption of afferent pathways that modulate sympathetic nervous system activity are likely to underlie some of the beneficial effects of renal denervation.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"57-69"},"PeriodicalIF":28.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368964","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

Multidisciplinary collaboration to improve neonatal kidney health 多学科合作改善新生儿肾脏健康

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-10-03 DOI: 10.1038/s41581-024-00895-1

Jennifer R. Charlton, David T. Selewski, Matthew W. Harer, David J. Askenazi, Michelle C. Starr, Ronnie Guillet, on behalf of the Board of the Neonatal Kidney Collaborative

引用次数: 0

New AAV vector targets glomerular endothelial cells 以肾小球内皮细胞为靶标的新型 AAV 向量

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-27 DOI: 10.1038/s41581-024-00898-y

Monica Wang

引用次数: 0

Risk of kidney failure among patients with genetic kidney diseases 遗传性肾病患者出现肾衰竭的风险

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-25 DOI: 10.1038/s41581-024-00896-0

Susan J. Allison

引用次数: 0

Spatial transcriptomics of acute kidney injury 急性肾损伤的空间转录组学

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-25 DOI: 10.1038/s41581-024-00899-x

Susan J. Allison

引用次数: 0

Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease 处于慢性肾脏病炎症和纤维化交叉口的新陈代谢

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-17 DOI: 10.1038/s41581-024-00889-z

Verónica Miguel, Isaac W. Shaw, Rafael Kramann

{"title":"Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease","authors":"Verónica Miguel, Isaac W. Shaw, Rafael Kramann","doi":"10.1038/s41581-024-00889-z","DOIUrl":"10.1038/s41581-024-00889-z","url":null,"abstract":"Chronic kidney disease (CKD), defined as persistent (>3 months) kidney functional loss, has a growing prevalence (>10% worldwide population) and limited treatment options. Fibrosis driven by the aberrant accumulation of extracellular matrix is the final common pathway of nearly all types of chronic repetitive injury in the kidney and is considered a hallmark of CKD. Myofibroblasts are key extracellular matrix-producing cells that are activated by crosstalk between damaged tubules and immune cells. Emerging evidence indicates that metabolic alterations are crucial contributors to the pathogenesis of kidney fibrosis by affecting cellular bioenergetics and metabolite signalling. Immune cell functions are intricately connected to their metabolic characteristics, and kidney cells seem to undergo cell-type-specific metabolic shifts in response to damage, all of which can determine injury and repair responses in CKD. A detailed understanding of the heterogeneity in metabolic reprogramming of different kidney cellular subsets is essential to elucidating communication processes between cell types and to enabling the development of metabolism-based innovative therapeutic strategies against CKD. Kidney fibrosis is a key pathological process in chronic kidney disease. Here, the authors examine how the metabolic reprogramming of kidney immune and non-immune cells in response to injury can promote fibrosis and consider the potential of metabolism-targeted therapies for preventing the development and progression of kidney fibrosis.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"39-56"},"PeriodicalIF":28.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236209","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

Polygenic scores and their applications in kidney disease 多基因评分及其在肾病中的应用

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-13 DOI: 10.1038/s41581-024-00886-2

Atlas Khan, Krzysztof Kiryluk

{"title":"Polygenic scores and their applications in kidney disease","authors":"Atlas Khan, Krzysztof Kiryluk","doi":"10.1038/s41581-024-00886-2","DOIUrl":"10.1038/s41581-024-00886-2","url":null,"abstract":"Genome-wide association studies (GWAS) have uncovered thousands of risk variants that individually have small effects on the risk of human diseases, including chronic kidney disease, type 2 diabetes, heart diseases and inflammatory disorders, but cumulatively explain a substantial fraction of disease risk, underscoring the complexity and pervasive polygenicity of common disorders. This complexity poses unique challenges to the clinical translation of GWAS findings. Polygenic scores combine small effects of individual GWAS risk variants across the genome to improve personalized risk prediction. Several polygenic scores have now been developed that exhibit sufficiently large effects to be considered clinically actionable. However, their clinical use is limited by their partial transferability across ancestries and a lack of validated models that combine polygenic, monogenic, family history and clinical risk factors. Moreover, prospective studies are still needed to demonstrate the clinical utility and cost-effectiveness of polygenic scores in clinical practice. Here, we discuss evolving methods for developing polygenic scores, best practices for validating and reporting their performance, and the study designs that will empower their clinical implementation. We specifically focus on the polygenic scores relevant to nephrology and other chronic, complex diseases and review their key limitations, necessary refinements and potential clinical applications. Polygenic scores model the combined risk of multiple variants across the genome to identify individuals at inherited risk of complex diseases. This Review discusses evolving methods for developing polygenic scores and describes examples across a spectrum of disease traits.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"24-38"},"PeriodicalIF":28.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231346","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 pathogenesis of IgA nephropathy and implications for treatment IgA 肾病的发病机制和治疗意义

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-04 DOI: 10.1038/s41581-024-00885-3

Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt

{"title":"The pathogenesis of IgA nephropathy and implications for treatment","authors":"Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt","doi":"10.1038/s41581-024-00885-3","DOIUrl":"10.1038/s41581-024-00885-3","url":null,"abstract":"IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and represents an important cause of chronic kidney disease globally, with observational studies indicating that most patients are at risk of developing kidney failure within their lifetime. Several research advances have provided insights into the underlying disease pathogenesis, framed by a multi-hit model whereby an increase in circulating IgA1 that lacks galactose from its hinge region — probably derived from the mucosal immune system — is followed by binding of specific IgG and IgA antibodies, generating immune complexes that deposit within the glomeruli, which triggers inflammation, complement activation and kidney damage. Although treatment options are currently limited, new therapies are rapidly emerging that target different pathways, cells and mediators involved in the disease pathogenesis, including B cell priming in the gut mucosa, the cytokines APRIL and BAFF, plasma cells, complement activation and endothelin pathway activation. As more treatments become available, there is a realistic possibility of transforming the long-term outlook for many individuals with IgAN. IgA nephropathy (IgAN) is thought to result from multiple hits that culminate in immune complex deposition in the kidney. Here, the authors describe the latest insights into the pathogenesis of IgAN and how they have revealed novel therapeutic targets and approaches to this disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":"9-23"},"PeriodicalIF":28.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130690","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

A novel mechanism of sodium and fluid retention in liver disease 肝病中钠和液体潴留的新机制

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-09-03 DOI: 10.1038/s41581-024-00892-4

Ellen F. Carney

引用次数: 0