Linking Climate, Kidneys & Cognition

The Climate-Kidneys-Cognition (CKC) Working Group is an international, collaborative network of nephrologists, neuroscientists, epidemiologists, climate scientists and microbiome researchers dedicated to elucidating the biological mechanisms linking environmental change to kidney and brain health. The group published its integrative framework on global environmental change and the gut–kidney–brain axis in The Lancet Planetary Health (2026).

Kidney disease already affects approximately one in eight people globally and is projected to become the fifth leading cause of death by 2040. Extreme heat increases the risk of dehydration, hypovolaemia and thermal stress, which elevates the risk of heat-related kidney diseases such as acute kidney injury, kidney stones and accelerated chronic kidney disease. Recurrent heat exposure, dehydration and strenuous physical activity are central drivers of CKD of non-traditional origin, particularly in outdoor workers in tropical regions, and repeated subclinical episodes of heat-stress kidney injury might accumulate into progressive CKD even in otherwise healthy individuals.

Neurological disorders are the leading cause of disability and the second leading cause of death globally, and climate change is increasingly recognised as a risk amplifier. Extreme heat has been associated with impaired cognitive function - specifically reduced efficiency of information processing and working memory - and with increased stroke risk, exacerbation of mental health disorders, and worsening of symptoms in people with pre-existing neurodegenerative disease. Climate extremes also trigger psychosocial stress, increasing rates of anxiety, depression, sleep disorders and post-traumatic stress disorder.

When kidney function declines, protein-bound uremic toxins such as indoxyl sulphate and p-cresyl sulphate accumulate in the circulation. These toxins are both nephrotoxic and neurotoxic: indoxyl sulphate can loosen endothelial tight junctions, contributing to blood–brain barrier leakage in chronic and end-stage kidney disease, while other toxins disrupt the brain's excitatory–inhibitory balance and reduce neuronal energy. This contributes to cognitive impairment and dementia risk in people with chronic kidney disease. The kidney–brain axis is bidirectional: the brain's autonomic and circadian regulation also controls renal blood flow, sodium excretion and blood pressure.

Long-term exposure to fine particulate matter (PM2.5) is strongly linked to kidney injury and chronic kidney disease progression. Air pollution also harms brain health across the life course, with effects including increased risk of stroke, cognitive decline, dementia and Parkinson's disease, described prenatally, during neurodevelopment and in later life. PM2.5 can cross the placenta and affect organ development, and prenatal and early-life exposure to air pollutants has been associated with higher chronic kidney disease risk during adolescence.

The gut–kidney–brain axis is a bidirectional communication network linking the gastrointestinal tract, kidneys and central nervous system through metabolic, immune, endocrine and neural pathways. Gut microbes produce metabolites such as short-chain fatty acids that support epithelial barrier integrity and exert renoprotective and neuroprotective effects, while uremic toxins produced when kidney function declines can damage both gut barrier and brain. The CKC Working Group's framework, published in The Lancet Planetary Health, positions the integrity of the intestinal barrier and the blood–brain barrier as convergence and amplification points through which climatic and environmental stressors - heat, air pollution, food insecurity, infection and psychosocial stress - might drive multi-organ vulnerability. These proposed mechanisms require validation in longitudinal human studies.

Climate and environmental changes disproportionately affect vulnerable populations. Outdoor and agricultural workers in tropical regions face chronic heat and dehydration implicated in CKD of non-traditional origin. Children are vulnerable from before birth, during crucial periods of barrier maturation, immune development and organogenesis - prenatal exposures might reduce nephron endowment and affect neurodevelopment. Pregnancy amplifies vulnerability, with heat exposure increasing risks of preterm birth and gestational hypertension. Older adults and people with existing kidney disease or multiple comorbidities face increased risk from reduced thermoregulatory capacity, and the largest burden falls on low-income and middle-income regions where adaptive resources such as cooling, hydration and healthcare infrastructure are scarce.

The group's Lancet Planetary Health framework identifies research priorities including prospective cohort studies tracking climate-exposed populations over time, biomarker validation of gut and blood-brain barrier integrity, and targeted interventions to preserve gut–kidney–brain axis function alongside exposure reduction. The most immediately actionable policy responses are upstream: reducing environmental exposures through emissions legislation, securing access to safe water and nutritious food, improving sanitation infrastructure, and implementing occupational heat protection such as shaded rest breaks and revised work-rest cycles.

The CKC Working Group actively seeks collaboration with researchers, policymakers and funding organisations committed to planetary health - including data sharing, policy development and research support. Contact the group at info@climate-kidneys-cognition.org.