{"title":"The GLP-1 receptor agonist revolution comes to nephrology","authors":"Merlin C. Thomas, Mark E. Cooper","doi":"10.1038/s41581-024-00876-4","DOIUrl":"10.1038/s41581-024-00876-4","url":null,"abstract":"Glucagon-like peptide 1 receptor agonists improve glucose control, promote weight loss and reduce the risk of major cardiovascular events in people with type 2 diabetes mellitus. The FLOW study now provides unequivocal evidence of kidney protective effects with semaglutide in adults with type 2 diabetes mellitus and chronic kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790952","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}
{"title":"CD38 — a new target in renal immune disease","authors":"Ton J. Rabelink, Aiko P. J. de Vries","doi":"10.1038/s41581-024-00874-6","DOIUrl":"10.1038/s41581-024-00874-6","url":null,"abstract":"Targeting of CD38 has been posited as a potential therapeutic avenue for the treatment of immune-mediated conditions. A phase 2 study now reports promising safety, tolerability and intermediate endpoint of efficacy outcomes with the anti-CD38 monoclonal antibody felzartamab in kidney transplant recipients with antibody-mediated rejection.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752181","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}
{"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":null,"pages":null},"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}
{"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":null,"pages":null},"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}
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":null,"pages":null},"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}
{"title":"Deep learning applications in digital pathology","authors":"Peter Boor","doi":"10.1038/s41581-024-00870-w","DOIUrl":"10.1038/s41581-024-00870-w","url":null,"abstract":"Deep Learning (DL) holds great promise to improve patient outcomes by improving the precision and speed of disease diagnosis and treatment recommendations. Given the efficacy of DL in image analysis, pathology will likely be one of the first medical fields transformed by DL. However, several challenges must be overcome before we can expect to see the use of DL transform the digital future of pathology.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625027","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}
{"title":"Treatment of chronic kidney disease in older populations","authors":"Seiji Kishi, Hiroyuki Kadoya, Naoki Kashihara","doi":"10.1038/s41581-024-00854-w","DOIUrl":"10.1038/s41581-024-00854-w","url":null,"abstract":"As the world population ages, an expected increase in the prevalence of chronic kidney disease (CKD) among older individuals will pose a considerable challenge for health care systems in terms of resource allocation for disease management. Treatment strategies for older patients with CKD should ideally align with those applied to the general population, focusing on minimizing cardiovascular events and reducing the risk of progression to kidney failure. Emerging therapies, such as SGLT-2 inhibitors and GLP-1 receptor agonists, hold promise for the effective management of CKD in older individuals. In addition, non-pharmacological interventions such as nutritional and exercise therapies have a crucial role. These interventions enhance the effects of pharmacotherapy and, importantly, contribute to the maintenance of cognitive function and overall quality of life. Various factors beyond age and cognitive function must be taken into account when considering kidney replacement therapy for patients with kidney failure. Importantly, all treatment options, including dialysis, transplantation and conservative management approaches, should be tailored to the individual through patient-centred decision-making. The dynamic integration of digital technologies into medical practice has the potential to transform the management of CKD in the aging population. Aging of the global population is expected to increase the prevalence of chronic kidney disease. This Review describes approaches to the management of kidney disease in older populations, highlighting the need for a holistic approach aimed at meeting the treatment goals of the patient.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":null,"pages":null},"PeriodicalIF":28.6,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556777","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}