Extreme heat exposure and all-cause mortality in patients with chronic kidney disease : A nationwide time-stratified case-crossover study of more than one million patients

As climate change (including global warming) intensifies the frequency and intensity of extreme weather events, ambient heat (high temperature) has emerged as a key factor determining global health risks. Chronic kidney disease (CKD), which affects approximately 10% of the world's population, is an important public health challenge as it contributes significantly to comorbidities and socioeconomic burdens. The kidneys play an essential role in maintaining fluid homeostasis and electrolyte balance. However, individuals with decreased kidney function are more susceptible to physiological vulnerabilities in situations of heat stress. Although it is known that patients with CKD may be vulnerable to environmental stress factors, including heat, large-scale empirical evidence to quantify the impact of ambient high temperature exposure as a clinical risk factor is still limited.

Using a national population-based dataset incorporating ERA-5 Land high-resolution reanalysis temperature data and National Health Insurance Service (NHIS) records in South Korea, this study investigated the association between extreme ambient heat and all-cause mortality in patients with CKD. Based on sex and age, 1,145,237 CKD patients with 1:1 matching with the non-CKD cohort were identified and bidirectional, time-stratified case-crossover study was conducted. Distributed Lag Non-linear Model (DLNM) was applied to capture nonlinear exposure-response relationships and lag effects (lag 0 to 6 days) together. Extreme heat was defined as the 99th percentile of the temperature distribution by district (si-gun-gu) and compared with the 75th percentile as the reference temperature (Temperature percentile was used to take into account regional temperature adaptations).

Analysis of 223,949 confirmed deaths in the CKD group revealed that extreme heat exposure was significantly associated with an increased risk of all-cause mortality (Odds Ratio[OR] 1.041; 95% CI 1.002–1.081; p=0.041). On the other hand, no significant association was observed in the matched non-CKD group (OR 0.993; 95% CI 0.951–1.036). Subgroup analysis revealed greater vulnerability in females, the elderly (≥65 years), and those with hypertension. These results suggest that heat stress may exacerbate vascular endothelial dysfunction and fluid volume dysregulation, especially in patients with decreased renal concentration capacity, thereby increasing the risk of fatal outcomes. Furthermore, sensitivity analysis with various model settings (alternative reference temperature, shorter lag structures) also confirmed the robustness of the results.

Taken together, this study provides a robust basis for supporting that CKD patients are disproportionately vulnerable to the negative effects of short-term extreme heat waves. From an interdisciplinary perspective, this study highlights the need for environmental risk profiling in CKD population groups. In a situation where the climate is warming more rapidly, it emphasizes the need for targeted prevention strategies such as customized heat wave-health alert systems and preemptive clinical monitoring to reduce the health burden on vulnerable CKD populations.