Nature Reviews Nephrology最新文献_第4页

Drug repurposing for glomerular diseases: an underutilized resource 肾小球疾病的药物再利用：未充分利用的资源

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-31 DOI: 10.1038/s41581-024-00864-8

Monica Suet Ying Ng, Gursimran Kaur, Ross S. Francis, Carmel M. Hawley, David W. Johnson

{"title":"Drug repurposing for glomerular diseases: an underutilized resource","authors":"Monica Suet Ying Ng, Gursimran Kaur, Ross S. Francis, Carmel M. Hawley, David W. Johnson","doi":"10.1038/s41581-024-00864-8","DOIUrl":"10.1038/s41581-024-00864-8","url":null,"abstract":"Drug repurposing in glomerular disease can deliver opportunities for steroid-free regimens, enable personalized multi-target options for resistant or relapsing disease and enhance treatment options for understudied populations (for example, children) and in resource-limited settings. Identification of drug-repurposing candidates can be data driven, which utilizes existing data on disease pathobiology, drug features and clinical outcomes, or experimental, which involves high-throughput drug screens. Information from databases of approved drugs, clinical trials and PubMed registries suggests that at least 96 drugs on the market cover 49 targets with immunosuppressive potential that could be candidates for drug repurposing in glomerular disease. Furthermore, evidence to support drug repurposing is available for 191 immune drug target–glomerular disease pairs. Non-immunological drug repurposing includes strategies to reduce haemodynamic overload, podocyte injury and kidney fibrosis. Recommended strategies to expand drug-repurposing capacity in glomerular disease include enriching drug databases with glomeruli-specific information, enhancing the accessibility of primary clinical trial data, biomarker discovery to improve participant selection into clinical trials and improve surrogate outcomes and initiatives to reduce patent, regulatory and organizational hurdles. Drug repurposing could expand the therapeutic options available to patients with glomerular disease. Here, the authors examine different approaches to the identification of drug candidates, consider current immunosuppressive and non-immunological options and discuss strategies to maximize drug repurposing in glomerular disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 11","pages":"707-721"},"PeriodicalIF":28.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857700","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

Anti-nephrin autoantibodies: a paradigm shift in podocytopathies 抗胰岛素自身抗体：荚膜细胞病的范式转变。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-30 DOI: 10.1038/s41581-024-00873-7

Zhao Cui, Ming-hui Zhao

引用次数: 0

Tertiary lymphoid organs contribute to kidney allograft rejection 三级淋巴器官导致肾脏异体移植排斥反应

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-29 DOI: 10.1038/s41581-024-00880-8

Ellen F. Carney

引用次数: 0

The GLP-1 receptor agonist revolution comes to nephrology 肾脏病学迎来 GLP-1 受体激动剂革命

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-29 DOI: 10.1038/s41581-024-00876-4

Merlin C. Thomas, Mark E. Cooper

引用次数: 0

Obesity promotes tumour growth by boosting PD1 levels on macrophages 肥胖会提高巨噬细胞上的 PD1 水平，从而促进肿瘤生长。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-26 DOI: 10.1038/s41581-024-00878-2

Monica Wang

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Ketogenic diet benefits in critically ill patients with sepsis 生酮饮食对败血症重症患者的益处。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-24 DOI: 10.1038/s41581-024-00877-3

Monica Wang

引用次数: 0

CD38 — a new target in renal immune disease CD38--肾脏免疫疾病的新靶点。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-23 DOI: 10.1038/s41581-024-00874-6

Ton J. Rabelink, Aiko P. J. de Vries

引用次数: 0

Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors G 蛋白偶联受体的空间、时间和配体偏倚的功能性后果

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-22 DOI: 10.1038/s41581-024-00869-3

András D. Tóth, Gábor Turu, László Hunyady

{"title":"Functional consequences of spatial, temporal and ligand bias of G protein-coupled receptors","authors":"András D. Tóth, Gábor Turu, László Hunyady","doi":"10.1038/s41581-024-00869-3","DOIUrl":"10.1038/s41581-024-00869-3","url":null,"abstract":"G protein-coupled receptors (GPCRs) regulate every aspect of kidney function by mediating the effects of various endogenous and exogenous substances. A key concept in GPCR function is biased signalling, whereby certain ligands may selectively activate specific pathways within the receptor’s signalling repertoire. For example, different agonists may induce biased signalling by stabilizing distinct active receptor conformations — a concept that is supported by advances in structural biology. However, the processes underlying functional selectivity in receptor signalling are extremely complex, involving differences in subcellular compartmentalization and signalling dynamics. Importantly, the molecular mechanisms of spatiotemporal bias, particularly its connection to ligand binding kinetics, have been detailed for GPCRs critical to kidney function, such as the AT1 angiotensin receptor (AT1R), V2 vasopressin receptor (V2R) and the parathyroid hormone 1 receptor (PTH1R). This expanding insight into the multifaceted nature of biased signalling paves the way for innovative strategies for targeting GPCR functions; the development of novel biased agonists may represent advanced pharmacotherapeutic approaches to the treatment of kidney diseases and related systemic conditions, such as hypertension, diabetes and heart failure. G protein-coupled receptors (GPCRs) elicit cellular responses to an array of stimuli to regulate the function of virtually all organs. The diverse functions of GPCRs are determined by their expression profiles and their ability to adopt different active and inactive conformations, resulting in functional selectivity or biased signalling. This Review describes the mechanisms and consequences of biased GPCR signalling with a focus on GPCRs of relevance to the kidney.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 11","pages":"722-741"},"PeriodicalIF":28.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736914","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

Pathological mechanisms of kidney disease in ageing 老龄化肾病的病理机制。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-18 DOI: 10.1038/s41581-024-00868-4

Takeshi Yamamoto, Yoshitaka Isaka

{"title":"Pathological mechanisms of kidney disease in ageing","authors":"Takeshi Yamamoto, Yoshitaka Isaka","doi":"10.1038/s41581-024-00868-4","DOIUrl":"10.1038/s41581-024-00868-4","url":null,"abstract":"The kidney is a metabolically active organ that requires energy to drive processes such as tubular reabsorption and secretion, and shows a decline in function with advancing age. Various molecular mechanisms, including genomic instability, telomere attrition, inflammation, autophagy, mitochondrial function, and changes to the sirtuin and Klotho signalling pathways, are recognized regulators of individual lifespan and pivotal factors that govern kidney ageing. Thus, mechanisms that contribute to ageing not only dictate renal outcomes but also exert a substantial influence over life expectancy. Conversely, kidney dysfunction, in the context of chronic kidney disease (CKD), precipitates an expedited ageing trajectory in individuals, leading to premature ageing and a disconnect between biological and chronological age. As CKD advances, age-related manifestations such as frailty become increasingly conspicuous. Hence, the pursuit of healthy ageing necessitates not only the management of age-related complications but also a comprehensive understanding of the processes and markers that underlie systemic ageing. Here, we examine the hallmarks of ageing, focusing on the mechanisms by which they affect kidney health and contribute to premature organ ageing. We also review diagnostic methodologies and interventions for premature ageing, with special consideration given to the potential of emerging therapeutic avenues to target age-related kidney diseases. The ability of the kidney to function normally declines with advancing age. This Review describes ageing processes that are relevant to age-related kidney diseases and the pathological mechanisms of chronic kidney disease in the context of premature ageing, as well as implications for diagnostic and therapeutic interventions.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 9","pages":"603-615"},"PeriodicalIF":28.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723972","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 population ageing on the burden of chronic kidney disease 人口老龄化对慢性肾病负担的影响。

IF 28.6 1区医学

Nature Reviews Nephrology Pub Date : 2024-07-18 DOI: 10.1038/s41581-024-00863-9

Nicholas C. Chesnaye, Alberto Ortiz, Carmine Zoccali, Vianda S. Stel, Kitty J. Jager

{"title":"The impact of population ageing on the burden of chronic kidney disease","authors":"Nicholas C. Chesnaye, Alberto Ortiz, Carmine Zoccali, Vianda S. Stel, Kitty J. Jager","doi":"10.1038/s41581-024-00863-9","DOIUrl":"10.1038/s41581-024-00863-9","url":null,"abstract":"The burden of chronic kidney disease (CKD) and its risk factors are projected to rise in parallel with the rapidly ageing global population. By 2050, the prevalence of CKD category G3–G5 may exceed 10% in some regions, resulting in substantial health and economic burdens that will disproportionately affect lower-income countries. The extent to which the CKD epidemic can be mitigated depends largely on the uptake of prevention efforts to address modifiable risk factors, the implementation of cost-effective screening programmes for early detection of CKD in high-risk individuals and widespread access and affordability of new-generation kidney-protective drugs to prevent the development and delay the progression of CKD. Older patients require a multidisciplinary integrated approach to manage their multimorbidity, polypharmacy, high rates of adverse outcomes, mental health, fatigue and other age-related symptoms. In those who progress to kidney failure, comprehensive conservative management should be offered as a viable option during the shared decision-making process to collaboratively determine a treatment approach that respects the values and wishes of the patient. Interventions that maintain or improve quality of life, including pain management and palliative care services when appropriate, should also be made available. Here, the authors examine the effect of the rapidly ageing global population on the health and economic burden of chronic kidney disease (CKD). They discuss factors that drive or could mitigate the CKD epidemic and highlight complications and symptoms of CKD that are common among older patients.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 9","pages":"569-585"},"PeriodicalIF":28.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723973","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