Reviews & Analysis

Two studies have applied a mechanical stimulus directly to a cilium, independent of a chemical signal, and demonstrated that force-based bending of a single nodal axoneme is sufficient to induce intraciliary Ca²⁺ flux in a PKD2-dependent manner, which propagates to drive asymmetric gene expression.

In this Review, the authors describe the roles of lysosomes in cellular clearance, autophagy, cell signalling, nutrient sensing and metabolic adaptation. They also discuss lysosome abnormalities in metabolic and autoimmune diseases and potential lysosome-targeting therapeutic strategies.

Sepsis-associated acute kidney injury (SA-AKI) is linked with poor outcomes in critically ill patients. This Consensus Statement from the Acute Disease Quality Initiative discusses the definition, epidemiology and pathophysiology of SA-AKI, fluid, resuscitation and extracorporeal therapies, and the role of biomarkers in risk stratification and diagnosis.

The DNA damage response is essential to genomic stability. Here, the authors discuss DNA damage-induced nephrotoxicity and kidney cancer, and the essential role of DNA repair in kidney homeostasis, as well as its potential to contribute to kidney dysfunction, including the links between DNA damage, cell-cycle control and ciliopathies.

An estimated 10–15% of individuals with hypertension are resistant to available antihypertensive therapies. Findings from two new clinical trials — BrigHTN and PRECISION — that assessed the blood pressure-lowering effects of the aldosterone synthase inhibitor baxdrostat and the dual endothelin receptor antagonist aprocitentan, respectively, suggest these approaches hold promise for patients with treatment-resistant hypertension.

This Review discusses the potential mechanisms by which regular exercise has beneficial effects on chronic inflammation, cardiovascular health, lipid metabolism, insulin resistance, sarcopenia and bone health in people with kidney disease. The authors highlight areas for further investigation to enhance the benefits of exercise for this population.

Any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health. Here, the authors discuss the effects of preterm birth and/or intrauterine growth restriction on kidney development and the impact of these exposures on the later development of chronic kidney disease.

Immune dysregulation contributes to the pathogenesis of preeclampsia. Here, the authors examine the role of immune cells and mediators in driving the oxidative stress and endothelial dysfunction that characterize this hypertensive disorder of pregnancy.

The gut microbiota is increasingly recognized as an important factor in human health and disease. Here, the authors focus on the role of the gut microbiome in blood pressure regulation and discuss its clinical implications, as well as the challenges and potential of microbiome research.

In this Review, the authors discuss the mineral-related factors and kidney-derived molecules that regulate osteocyte FGF23 production in health and disease. They also highlight potential approaches to the treatment of FGF23-related disorders of mineral metabolism that target key bone–kidney interactions.

Primary hyperoxaluria is an inherited disorder that results from the overproduction of endogenous oxalate, leading to recurrent kidney stones, nephrocalcinosis, kidney failure and life-threatening systemic disease. This Consensus Statement from ERKNet and OxalEurope provides recommendations for the management of primary hyperoxaluria, including consideration of conventional therapies, new therapies and recommendations for patient follow-up.

Necroptosis is a form of necrotic cell death that leads to cell lysis and an inflammatory response in neighbouring tissues. This Review describes the molecular mechanisms that regulate the induction of necroptosis and current evidence implicating a role for necroptosis in the pathogenesis of kidney diseases.

Pyroptosis is a form of regulated cell death that is mediated by the membrane-targeting, pore-forming gasdermin family of proteins. Here, the authors provide an overview of the basic biology of gasdermins and pyroptosis with a focus on the mechanisms by which these proteins may contribute to kidney disease.

More than three-quarters of cases of chronic kidney disease are caused by glomerular diseases with glomerulosclerosis, including diabetic kidney disease, hypertensive nephropathy and glomerulonephritis. Studies in 2022 provided insights into the molecular mechanisms that maintain dynamic glomerular structures and the responses of specific glomerular cell types during glomerular disease.

Acute kidney injury (AKI) is a multifactorial syndrome with a complex pathophysiology including different inflammatory cells and mediators. Current research focuses on identifying key contributing pathways, determining high-risk groups, characterizing AKI sub-phenotypes and investigating strategies for therapeutic interventions.

Studies in 2022 have advanced knowledge of pregnancy outcomes in kidney donors and transplant recipients as well as the long-term risks associated with hypertensive disorders of pregnancy. These findings should be used to support shared decision-making and appropriate care of women with or at risk of kidney disease.

Over the past year, trial data have emerged on therapeutic interventions in IgA nephropathy and lupus nephritis, including the effects of different doses of glucocorticoids and several novel targeted therapies. These data, in combination with the discovery of autoantibodies targeting nephrin in minimal change disease, can inform the management of immune-mediated glomerular diseases.

Kidney transplantation is the best therapy for kidney failure, but is limited by donor organ availability and the risks associated with immunosuppression. Studies in 2022 provided encouraging data about the outcomes of COVID-19 among transplant recipients, the effects of changes to organ allocation policy in the US and progress in xenotransplantation, raising hope that the organ shortage can be solved.

Chronic kidney disease (CKD) is known to be associated with cognitive impairment, but the mechanisms that underlie this kidney–brain connection are unclear. A recent study provides evidence that CKD is an independent risk factor for cognitive decline due to cerebral small vessel disease.

Inter-organ interactions are critical for maintaining homeostasis in the body but can contribute to multi-organ dysfunction. Clinical evidence indicates that kidney dysfunction contributes to remote organ dysfunction, but little is known of the underlying mechanisms. Several reports published in 2022 identified critical mediators of kidney crosstalk with distant organs.