Reviews & Analysis

Here, the authors discuss the pathophysiology of pre-eclampsia and potential targets for treatment to reduce maternal and perinatal mortality. They also discuss the utility of testing to predict pre-eclampsia and the pathogenesis of cardiovascular disease following pre-eclamptic pregnancy.

Many glomerular diseases have a genetic basis; however, not all identified variants are pathogenic. This Expert Recommendation from the Clinical Genome Resource (ClinGen) Glomerulopathy Gene Curation Expert Panel describes the outcomes of gene curation efforts to evaluate the evidence underlying asserted gene–disease relationships for 56 genes that have putatively been linked to glomerular diseases.

Current gaps in the management of anti-neutrophil cytoplasmic antibody-associated vasculitis include treatment-associated morbidity and mortality risk. Here, the authors examine research findings on biological readouts of disease activity that might offer biomarkers for monitoring disease activity and inform therapeutic interventions.

Here, the authors describe organelle-specific autophagy pathways and explain how renal cells integrate metabolic and stress signals to shape cargo selection and organelle quality control. They also discuss translational challenges in targeting selective autophagy pathways in kidney disease.

The cardiovascular–kidney–metabolic (CKM) syndrome paradigm is aimed at reflecting the complex interactions between chronic kidney disease, cardiovascular disease and metabolic dysfunction. Here, the authors discuss current CKM syndrome epidemiological data, examine key determinants of CKM health and consider the potential clinical implications and limitations of the CKM syndrome framework.

In this Review, the authors discuss how pathophysiological mechanisms in chronic kidney disease contribute to an increased susceptibility to the negative consequences of high dietary salt intake and how excess salt can contribute to progressive renal function decline and hypertension.

Acute kidney injury and chronic kidney disease are closely associated with mitochondrial dysfunction. Here, the authors discuss the role of mitochondria in kidney homeostasis and disease, and examine the potential of mitochondrial transplantation as a therapeutic approach to mitigating kidney injury-associated cellular dysfunction, including technical considerations for kidney applications.

Air pollution is a major global health concern, with widespread effects on morbidity and mortality. This Review describes the epidemiological evidence linking atmospheric stressors, including particulate matter, ozone, nitrogen dioxide, wildfire smoke and extreme temperatures, to kidney disease, and explores future research directions to better understand the role of atmospheric conditions on kidney health.

Here, DeFronzo and colleagues explore the underappreciated adverse effects of insulin resistance and accompanying hyperinsulinaemia on the kidney, which is an insulin-responsive organ and has an important role in insulin homeostasis. The authors examine the interplay between insulin dysregulation, lipid metabolism and inflammation, and consider emerging therapies to address this metabolic dysfunction.

The kidney contains a heterogeneous endothelial cell population that serve distinct roles in the maintenance of tissue homeostasis and kidney function. This Review summarizes current understanding of the endothelial response to kidney injury, focusing on the response of vascular, glomerular and lymphatic endothelial cells in diverse kidney diseases, and describes the potential of emerging endothelium-targeted therapeutics to ameliorate injury and restore kidney function.

Here, the authors discuss explanations for missing disease-causing variants in Alport syndrome, how clinicians and laboratories might manage missing variants and how to care for patients when a clinical suspicion of Alport syndrome exists but no disease-causing variant has been identified.

Advances in artificial intelligence-driven algorithms and experimental technologies have revolutionized the field of protein modelling. This Review describes how these developments have provided unprecedented insights into the structure of key proteins within the kidney, improved understanding of the relationships between protein structure and stability, and enabled mechanistic interpretation of variants that underlie a variety of kidney pathologies.

Social determinants of health can have a considerable impact on patient outcomes. Here, the authors examine how social determinants of health contribute to the growing global burden of acute kidney injury and its inequities, and discuss key strategies for tackling disparities in acute kidney injury care and outcomes.

This Review discusses key strategies for managing patients with advanced chronic kidney disease progressing towards kidney failure. The authors examine drug and lifestyle interventions that can mitigate kidney and cardiovascular risks, and options for addressing kidney failure, including transplantation, dialysis and conservative kidney care, with an emphasis on informed shared decision-making.

In this Review, the authors discuss the physiological determinants of blood potassium levels, the health consequences of chronic hypokalaemia and hyperkalaemia, and the potential cardiorenal benefits of potassium supplementation. They also highlight strategies to reduce the risk of hyperkalaemia and enable patients with chronic kidney disease to consume a potassium-rich diet.

This Review examines the bidirectional relationship between mental health conditions, particularly depression, anxiety and severe mental illness, and chronic kidney disease. The authors discuss the impact of these comorbid conditions; provide insights and recommendations on patient management, with a focus on integrated care; and highlight key research gaps.

The aetiological and epidemiological landscapes of chronic kidney disease and acute kidney injury are influenced by non-medical factors, known as the social determinants of health (SDH). This Review describes how SDH shape the landscape of kidney diseases, using case studies to explore how these factors, including those associated with urbanization, can alter the aetiology and epidemiology of kidney disease.

Dialysis is among the most cost-intensive health services available; however, its availability is often shaped by competing interests among providers, payers, industry and patients. Thailand’s experience in aligning these interests offers valuable lessons for countries that are striving to expand equitable kidney care within limited fiscal space and progress towards universal health coverage.

In this Review, the authors discuss guideline-directed medical therapy for diabetic kidney disease and the evolving clinical evidence for next-generation therapies, including incretin-based therapies, endothelin receptor antagonists, aldosterone synthase inhibitors, soluble guanylate cyclase agonists and anti-inflammatory therapies.

Targeting incretins is emerging as an effective approach to treat cardiovascular–kidney–metabolic syndrome. Here, the authors examine the biological effects of incretins and other metabolic hormones, such as glucagon and amylin, as well as discussing current clinical data demonstrating the organ-protective effects of incretin drugs and their potential underlying mechanisms.