Pub Date : 2026-01-12DOI: 10.1038/s41581-025-01042-0
Tae Won Yi,Vikas S Sridhar,Jennifer Scott,Massimo Nardone,David Cherney
Diabetes mellitus is the leading cause of chronic kidney disease and kidney failure worldwide, and diabetic kidney disease (DKD) is associated with excess cardiovascular and all-cause mortality. The pathophysiology of DKD is complex and multifactorial, characterized by physiologically redundant haemodynamic, metabolic and inflammatory pathways that promote maladaptive renal remodelling and accelerate disease progression. Current management of DKD centres around four key pillars of guideline-directed medical therapy (GDMT): renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, non-steroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. These therapies are increasingly used in combination for cardiorenal protection in DKD. However, substantial residual cardiorenal risk persists even among patients receiving optimal GDMT. Next-generation therapies for DKD that are currently in development include various incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory agents. These therapies are expected to complement current GDMT and further improve kidney and cardiovascular outcomes in patients with DKD.
{"title":"Next-generation therapeutics for diabetic kidney disease.","authors":"Tae Won Yi,Vikas S Sridhar,Jennifer Scott,Massimo Nardone,David Cherney","doi":"10.1038/s41581-025-01042-0","DOIUrl":"https://doi.org/10.1038/s41581-025-01042-0","url":null,"abstract":"Diabetes mellitus is the leading cause of chronic kidney disease and kidney failure worldwide, and diabetic kidney disease (DKD) is associated with excess cardiovascular and all-cause mortality. The pathophysiology of DKD is complex and multifactorial, characterized by physiologically redundant haemodynamic, metabolic and inflammatory pathways that promote maladaptive renal remodelling and accelerate disease progression. Current management of DKD centres around four key pillars of guideline-directed medical therapy (GDMT): renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, non-steroidal mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists. These therapies are increasingly used in combination for cardiorenal protection in DKD. However, substantial residual cardiorenal risk persists even among patients receiving optimal GDMT. Next-generation therapies for DKD that are currently in development include various incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory agents. These therapies are expected to complement current GDMT and further improve kidney and cardiovascular outcomes in patients with DKD.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"49 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956060","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}
Pub Date : 2026-01-08DOI: 10.1038/s41581-025-01036-y
Radica Z Alicic, Joshua J Neumiller, Katherine R Tuttle
Chronic kidney disease (CKD) remains a major public health problem, with type 2 diabetes and obesity representing key risk factors worldwide. The complex pathophysiology and the metabolic risk factors shared between type 2 diabetes, obesity, CKD and cardiovascular disease have led to the concept of a cardiovascular-kidney-metabolic (CKM) syndrome. The treatment landscape for CKM changed dramatically when agents from several medication classes, originally developed as glucose-lowering therapies, were recognized to reduce the risk of multiple components of CKM syndrome. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic-GLP-1RAs, have evolved from metabolic therapies to agents with either proven or potential protective effects on the kidney and heart. In addition to their potent metabolic actions that reduce hyperglycaemia and body weight, GLP-1RAs also lower the risk of major kidney, cardiovascular and mortality outcomes across broad populations with cardiovascular disease or CKD, with and without diabetes or obesity. GLP-1RAs have been combined with glucose-dependent insulinotropic agonism, as well as glucagon agonism or amylin analogues to further enhance their metabolic benefits. However, kidney and heart protection are not fully explainable by the metabolic actions of these agents. Rather, a growing body of evidence suggests that the systemic and local actions of incretins and metabolic hormones modulate multiple pathways that can promote inflammatory and fibrotic injury.
{"title":"GLP-1 receptor agonists and next-generation metabolic hormone therapies in chronic kidney disease.","authors":"Radica Z Alicic, Joshua J Neumiller, Katherine R Tuttle","doi":"10.1038/s41581-025-01036-y","DOIUrl":"https://doi.org/10.1038/s41581-025-01036-y","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) remains a major public health problem, with type 2 diabetes and obesity representing key risk factors worldwide. The complex pathophysiology and the metabolic risk factors shared between type 2 diabetes, obesity, CKD and cardiovascular disease have led to the concept of a cardiovascular-kidney-metabolic (CKM) syndrome. The treatment landscape for CKM changed dramatically when agents from several medication classes, originally developed as glucose-lowering therapies, were recognized to reduce the risk of multiple components of CKM syndrome. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic-GLP-1RAs, have evolved from metabolic therapies to agents with either proven or potential protective effects on the kidney and heart. In addition to their potent metabolic actions that reduce hyperglycaemia and body weight, GLP-1RAs also lower the risk of major kidney, cardiovascular and mortality outcomes across broad populations with cardiovascular disease or CKD, with and without diabetes or obesity. GLP-1RAs have been combined with glucose-dependent insulinotropic agonism, as well as glucagon agonism or amylin analogues to further enhance their metabolic benefits. However, kidney and heart protection are not fully explainable by the metabolic actions of these agents. Rather, a growing body of evidence suggests that the systemic and local actions of incretins and metabolic hormones modulate multiple pathways that can promote inflammatory and fibrotic injury.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":" ","pages":""},"PeriodicalIF":39.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934473","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}
Pub Date : 2026-01-05DOI: 10.1038/s41581-025-01034-0
Juan J. Carrero, David E. St-Jules, Annabel Biruete, Lilian Cuppari, Giorgina B. Piccoli, Kelly Picard, Nikita M. Hansen, Alice Sabatino, Dillon Winkelman, Carla M. Avesani
{"title":"Quality-oriented diet therapy for chronic kidney disease","authors":"Juan J. Carrero, David E. St-Jules, Annabel Biruete, Lilian Cuppari, Giorgina B. Piccoli, Kelly Picard, Nikita M. Hansen, Alice Sabatino, Dillon Winkelman, Carla M. Avesani","doi":"10.1038/s41581-025-01034-0","DOIUrl":"https://doi.org/10.1038/s41581-025-01034-0","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"39 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903329","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}
Pub Date : 2026-01-05DOI: 10.1038/s41581-025-01038-w
Paola Romagnani, Juliana C. N. Chan, Hans-Joachim Anders
{"title":"Multifactorial chronic kidney disease and the kidney capacity–workload balance","authors":"Paola Romagnani, Juliana C. N. Chan, Hans-Joachim Anders","doi":"10.1038/s41581-025-01038-w","DOIUrl":"https://doi.org/10.1038/s41581-025-01038-w","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"83 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902545","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}
Pub Date : 2025-12-17DOI: 10.1038/s41581-025-01045-x
Ying Chen, Li Yang
Kidneys are highly susceptible to acute injury. Several studies in 2025 revealed insights into mechanisms of protection and susceptibility — including sex-specific mechanisms of protection against ferroptosis, mechanisms of impaired resilience imparted by mitochondrial DNA mutations, and a role for tRNA-Asp-GTC-3′tDR in RNA autophagy — that provide new directions for diagnostic tools and therapies for acute kidney injury.
{"title":"Toward an understanding of the intrinsic kidney response to acute injury","authors":"Ying Chen, Li Yang","doi":"10.1038/s41581-025-01045-x","DOIUrl":"10.1038/s41581-025-01045-x","url":null,"abstract":"Kidneys are highly susceptible to acute injury. Several studies in 2025 revealed insights into mechanisms of protection and susceptibility — including sex-specific mechanisms of protection against ferroptosis, mechanisms of impaired resilience imparted by mitochondrial DNA mutations, and a role for tRNA-Asp-GTC-3′tDR in RNA autophagy — that provide new directions for diagnostic tools and therapies for acute kidney injury.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 2","pages":"97-98"},"PeriodicalIF":39.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770752","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}
Pub Date : 2025-12-16DOI: 10.1038/s41581-025-01044-y
Yelena Drexler, Alessia Fornoni
Cardiovascular–kidney–metabolic (CKM) syndrome reflects the intricate connections between metabolic disorders, chronic kidney disease and cardiovascular disease. In 2025, key studies advanced understanding of risk prediction in CKM syndrome, including the role of social determinants of health, as well as combination treatment strategies and potential therapeutic targets to improve CKM health.
{"title":"Advances in risk prediction and treatment strategies for CKM syndrome","authors":"Yelena Drexler, Alessia Fornoni","doi":"10.1038/s41581-025-01044-y","DOIUrl":"10.1038/s41581-025-01044-y","url":null,"abstract":"Cardiovascular–kidney–metabolic (CKM) syndrome reflects the intricate connections between metabolic disorders, chronic kidney disease and cardiovascular disease. In 2025, key studies advanced understanding of risk prediction in CKM syndrome, including the role of social determinants of health, as well as combination treatment strategies and potential therapeutic targets to improve CKM health.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"22 2","pages":"95-96"},"PeriodicalIF":39.8,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765445","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}
Pub Date : 2025-12-15DOI: 10.1038/s41581-025-01043-z
Nicholas Lucarelli
{"title":"Interactive exploration of multimodal spatial data with FUSION.","authors":"Nicholas Lucarelli","doi":"10.1038/s41581-025-01043-z","DOIUrl":"https://doi.org/10.1038/s41581-025-01043-z","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"66 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759995","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}
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