An epidemic of chronic kidney disease of unknown etiology (Mesoamerican Nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent heat exposure causes chronic kidney disease in animal models. However, the independent influence of the core body temperature to kidney injury has not been explored. Here we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature.
Wild type mice were exposed heat (39.5°C, 30 min, 2 times daily) with or without the mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP) for 10 days. Core temperature, renal function, proteinuria, renal histological and biochemical analyses were performed. Isolated mitochondria markers of oxidative stress were evaluated from kidney tissue.
DNP increased the body core temperature in response to heat by 1 degree C (42 versus 41) that was transient. The mild increase in temperature correlated with worsening albuminuria (R=0.715, p<001), renal tubular injury and interstitial infiltration of monocyte/macrophages. The tubular injury was marked in the outer medulla. This was associated with a reduction in kidney tissue ATP levels (nonheated control 16.71±1.33nmol/mg, DNP+Heat 13.08±1.12nmol/mg, p<0.01), reduced mitochondria, and evidence for mitochondrial oxidative stress.
These studies suggest that kidney injury in heat stress is markedly worsened by increasing core temperature. The studies are consistent with the hypothesis that clinical and subclinical heat stroke may play a role in Mesoamerican Nephropathy.