The case for cardiovascular–kidney–liver–metabolic syndrome

Nature Reviews Nephrology, Published online: 08 October 2026; doi:10.1038/s41581-026-01137-2The liver has a central role in cardiovascular–kidney–metabolic syndrome but is absent from the current definition. A cardiovascular–kidney–liver–metabolic framework that recognizes steatotic liver disease as both a consequence and an amplifier of multi-organ damage could improve risk prediction and facilitate the development of new therapies.

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Sex and gender in cardiovascular–kidney–metabolic health: strengthening the evidence

Nature Reviews Nephrology, Published online: 06 October 2026; doi:10.1038/s41581-026-01141-6Sex- and gender-associated factors shape cardiovascular–kidney–metabolic (CKM) health. Optimizing CKM care requires studies that are designed to detect clinically meaningful sex and gender differences, measure the biological and sociocultural factors that may influence risk and response to treatment, and use comparator groups that help to determine how exposures, conditions, and interventions influence CKM health across populations.

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Preventative nephrology in the cardiovascular–kidney–metabolic era

Nature Reviews Nephrology, Published online: 05 October 2026; doi:10.1038/s41581-026-01140-7Although major therapeutic advances have transformed chronic kidney disease (CKD) treatment, healthcare delivery remains largely organized around individual diseases and advanced CKD. The cardiovascular–kidney–metabolic framework provides an opportunity for nephrology to shift from reactive care towards preserving kidney health through early detection, kidney-protective therapies and coordinated multidisciplinary care delivery.

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Metabolic control by liver–kidney crosstalk and glucagon in health and disease

Nature Reviews Nephrology, Published online: 29 September 2026; doi:10.1038/s41581-026-01111-yGluconeogenesis, nitrogen metabolism and acid–base regulation are fundamental for the maintenance of metabolic homeostasis. This Review describes how these processes form an interconnected triangle, with liver–kidney crosstalk and the hormone glucagon at its core, and discusses how changes in these processes contribute to kidney, liver and metabolic disease.

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Targeting the aldosterone–mineralocorticoid receptor pathway in cardiovascular–kidney–metabolic syndrome

Nature Reviews Nephrology, Published online: 28 September 2026; doi:10.1038/s41581-026-01125-6The aldosterone–mineralocorticoid receptor pathway promotes inflammation, fibrosis, oxidative stress and metabolic alterations. Here, the authors discuss evidence that suggests a role of this pathway as a central therapeutic target to reduce organ dysfunction and improve outcomes in cardiovascular–kidney–metabolic syndrome.

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Recommendations for the management of frailty in chronic kidney disease: a consensus report

Nature Reviews Nephrology, Published online: 25 September 2026; doi:10.1038/s41581-026-01128-3Frailty is highly prevalent in patients with chronic kidney disease (CKD) and is associated with increased mortality, hospitalization and disability and with poorer quality of life. This Consensus Statement provides recommendations across four domains covering the assessment of frailty, interventions aimed at targeting the modifiable contributors to frailty in patients with CKD, considerations related to conservative kidney management and kidney replacement therapy, and the management of stage 5 CKD in the presence of frailty.

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Cardiovascular–kidney–metabolic syndrome as a mitochondrial systems disorder

Nature Reviews Nephrology, Published online: 24 September 2026; doi:10.1038/s41581-026-01127-4In this Review, the authors propose a mitochondria-centred, systems-level interpretation of cardiovascular–kidney–metabolic (CKM) syndrome. They highlight mitochondrial ‘failure modes’ that recur across organs, inter-organ routes by which mitochondrial stress can be sensed or communicated and opportunities for clinical translation.

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An integrated single-cell atlas of hypertension

Nature Reviews Nephrology, Published online: 24 September 2026; doi:10.1038/s41581-026-01135-4An integrated single-cell atlas of hypertension

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Metabolic control by liver–kidney crosstalk and glucagon in health and disease

Nature Reviews Nephrology, Published online: 29 September 2026; doi:10.1038/s41581-026-01111-yGluconeogenesis, nitrogen metabolism and acid–base regulation are fundamental for the maintenance of metabolic homeostasis. This Review describes how these processes form an interconnected triangle, with liver–kidney crosstalk and the hormone glucagon at its core, and discusses how changes in these processes contribute to kidney, liver and metabolic disease.

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The role of senescence in kidney ageing, injury and fibrosis

Nature Reviews Nephrology, Published online: 23 September 2026; doi:10.1038/s41581-026-01123-8This Review examines the dual role of cellular senescence as a crucial physiological process and a potential contributor to kidney ageing and disease. The authors also discuss key considerations for targeting senescence therapeutically in humans and the need to address the current evidence gap between experimental studies and human disease.

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The kidney research community is letting down patients by failing to collaborate enough. Discuss. | Kidney Research UK | 33 comments

The kidney research community needs to change. We're all passionate experts. We care deeply. But we're not seeing the progress that kidney patients need. To be blunt, we need to do more, and faster....

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Targeting the aldosterone–mineralocorticoid receptor pathway in cardiovascular–kidney–metabolic syndrome

Nature Reviews Nephrology, Published online: 28 September 2026; doi:10.1038/s41581-026-01125-6The aldosterone–mineralocorticoid receptor pathway promotes inflammation, fibrosis, oxidative stress and metabolic alterations. Here, the authors discuss evidence that suggests a role of this pathway as a central therapeutic target to reduce organ dysfunction and improve outcomes in cardiovascular–kidney–metabolic syndrome.

dlvr.it

Enhanced urea uptake promotes bleeding in advanced CKD

Nature Reviews Nephrology, Published online: 22 September 2026; doi:10.1038/s41581-026-01134-5Enhanced urea uptake promotes bleeding in advanced CKD

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Primary cilia: master conductors of cellular communication in development and disease

Nature Reviews Nephrology, Published online: 21 September 2026; doi:10.1038/s41581-026-01129-2Ciliary dysfunction underlies a broad spectrum of ciliopathies that affect virtually all organ systems, including the kidney. In this Review, the authors discuss how primary cilia regulate signalling pathways in physiological and pathological contexts.

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Recommendations for the management of frailty in chronic kidney disease: a consensus report

Nature Reviews Nephrology, Published online: 25 September 2026; doi:10.1038/s41581-026-01128-3Frailty is highly prevalent in patients with chronic kidney disease (CKD) and is associated with increased mortality, hospitalization and disability and with poorer quality of life. This Consensus Statement provides recommendations across four domains covering the assessment of frailty, interventions aimed at targeting the modifiable contributors to frailty in patients with CKD, considerations related to conservative kidney management and kidney replacement therapy, and the management of stage 5 CKD in the presence of frailty.

dlvr.it

Cardiovascular–kidney–metabolic syndrome as a mitochondrial systems disorder

Nature Reviews Nephrology, Published online: 24 September 2026; doi:10.1038/s41581-026-01127-4In this Review, the authors propose a mitochondria-centred, systems-level interpretation of cardiovascular–kidney–metabolic (CKM) syndrome. They highlight mitochondrial ‘failure modes’ that recur across organs, inter-organ routes by which mitochondrial stress can be sensed or communicated and opportunities for clinical translation.

dlvr.it

An integrated single-cell atlas of hypertension

Nature Reviews Nephrology, Published online: 24 September 2026; doi:10.1038/s41581-026-01135-4An integrated single-cell atlas of hypertension

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Ferroptosis in kidney disease

Nature Reviews Nephrology, Published online: 18 September 2026; doi:10.1038/s41581-026-01131-8In this Review, the authors discuss the role of ferroptosis in kidney diseases including acute kidney injury, chronic kidney disease, renal cell carcinoma and polycystic kidney disease. They also highlight the potential of ferroptosis as an early pathological marker and a therapeutic target for the prevention and treatment of these diseases.

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Megalin: from structure to function

Nature Reviews Nephrology, Published online: 18 September 2026; doi:10.1038/s41581-026-01130-9Megalin and cubilin are the main endocytic receptors that bind and retrieve proteins that pass through the glomerular filtration barrier. This Review discusses advances in understanding megalin structure and proximal tubule endocytic pathway organization. It also examines emerging roles for megalin in transcriptional regulation, metabolism and susceptibility to kidney disease.

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The role of senescence in kidney ageing, injury and fibrosis

Nature Reviews Nephrology, Published online: 23 September 2026; doi:10.1038/s41581-026-01123-8This Review examines the dual role of cellular senescence as a crucial physiological process and a potential contributor to kidney ageing and disease. The authors also discuss key considerations for targeting senescence therapeutically in humans and the need to address the current evidence gap between experimental studies and human disease.

dlvr.it

Enhanced urea uptake promotes bleeding in advanced CKD

Nature Reviews Nephrology, Published online: 22 September 2026; doi:10.1038/s41581-026-01134-5Enhanced urea uptake promotes bleeding in advanced CKD

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Epidemiology, mechanisms and clinical implications of heat-related kidney disease

Nature Reviews Nephrology, Published online: 16 September 2026; doi:10.1038/s41581-026-01126-5Heat extremes associated with climate change are increasingly recognized to have adverse health effects. Here, the authors consider thermoregulatory physiology and examine the evidence connecting heat stress to kidney injury, as well as its potential impact on chronic kidney disease, highlighting research gaps and clinical implications.

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Primary cilia: master conductors of cellular communication in development and disease

Nature Reviews Nephrology, Published online: 21 September 2026; doi:10.1038/s41581-026-01129-2Ciliary dysfunction underlies a broad spectrum of ciliopathies that affect virtually all organ systems, including the kidney. In this Review, the authors discuss how primary cilia regulate signalling pathways in physiological and pathological contexts.

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Uprooting inequity: cultivating a flourishing and socially accountable nephrologist workforce for Indigenous peoples

Nature Reviews Nephrology, Published online: 15 September 2026; doi:10.1038/s41581-026-01133-6Indigenous peoples in Aotearoa New Zealand, Australia and the USA experience a disproportionate burden of kidney disease yet remain markedly underrepresented within the nephrologist workforce. These inequities reflect broad failures in institutional accountability. Addressing these failures requires reforms in workforce planning, training and governance, designed around social accountability and Indigenous partnership.

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City design for kidney health

Nature Reviews Nephrology, Published online: 14 September 2026; doi:10.1038/s41581-026-01132-7Approaches for the prevention of kidney disease focus mainly on clinical risk factors but overlook risks embedded in urban planning and governance. Urban policies should be treated as population-level, multisectoral interventions that have potential to influence chronic disease risk. Considerations around kidney health should inform the design of transport, housing and climate policies and be evaluated on the basis of health and equity outcomes.

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Ferroptosis in kidney disease

Nature Reviews Nephrology, Published online: 18 September 2026; doi:10.1038/s41581-026-01131-8In this Review, the authors discuss the role of ferroptosis in kidney diseases including acute kidney injury, chronic kidney disease, renal cell carcinoma and polycystic kidney disease. They also highlight the potential of ferroptosis as an early pathological marker and a therapeutic target for the prevention and treatment of these diseases.

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