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Ferroptosis is an iron-dependent mechanism of regulated necrosis that is driven by the robust oxidation of polyunsaturated fatty acid-containing phospholipids. This Review describes the fundamental mechanisms of ferroptosis, the potential contribution of ferroptosis to kidney disease and therapeutic strategies for targeting ferroptosis.
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.
Optimal referral of patients who are at risk of kidney failure to nephrologists could improve their long-term outcomes. Various strategies, including the inclusion of kidney failure risk equations in electronic medical records and the active dissemination of clinical practice guidelines, could help to reduce the gap between optimal referral and what currently happens in clinical practice.
Access to essential medical care can be compromised by social disruptions (such as riots and labour strikes), armed conflict and natural disasters, including extreme weather events. A successful response to such events requires forward planning, preparation and rehearsal with involvement of health-care systems, professionals, patients and their support networks. Following execution of the response, after-action evaluation is required to improve future responses.
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.
People with kidney disease are particularly vulnerable to the impacts of natural disasters and extreme weather events. As climate change is increasing the frequency and severity of these events, a robust response is needed to improve disaster preparedness and increase the resilience of these patients.
Thousands of environmental chemicals are used globally. However, despite clear evidence of their adverse effects on the kidney, substantial knowledge gaps remain. Further studies are needed to better understand the effects of chemical mixtures, windows of physiological susceptibility, vulnerable populations, and the intersection of chemical exposure with health risks associated with climate change and heat stress.
Climate change is increasing global temperatures and causing more frequent and severe extreme heat events. The resulting additional disease burden is inequitably distributed. Strategies that reduce inequities in heat exposure and vulnerability to heat-related illness, as well as health protections at multiple levels (from individual to regional), are urgently needed to contain the looming crisis.
