Metabolic and Kidney Diseases in the Setting of Climate Change, Water Shortage, and Survival Factors

Abstract

Climate change (global warming) is leading to an increase in heat extremes and coupled with increasing water shortage, provides a perfect storm for a new era of environmental crises and potentially, new diseases. We use a comparative physiologic approach to show that one of the primary mechanisms by which animals protect themselves against water shortage is to increase fat mass as a means for providing metabolic water. Strong evidence suggests that certain hormones (vasopressin), foods (fructose), and metabolic products (uric acid) function as survival signals to help reduce water loss and store fat (which also provides a source of metabolic water). These mechanisms are intricately linked with each other and stimulated by dehydration and hyperosmolarity. Although these mechanisms were protective in the setting of low sugar and low salt intake in our past, today, the combination of diets high in fructose and salty foods, increasing temperatures, and decreasing available water places these survival signals in overdrive and may be accelerating the obesity and diabetes epidemics. The recent discovery of multiple epidemics of CKD occurring in agricultural workers in hot and humid environments may represent harbingers of the detrimental consequences of the combination of climate change and overactivation of survival pathways.

Keywords: chronic kidney disease; metabolism; obesity; osmolality; vasopressin.

Figure 1.

Vasopressin, the ultimate survival hormone. Vasopressin may have originated as a survival hormone for situations where the organism suffered from either extracellular volume or intracellular volume loss. The effects of vasopressin include actions much greater than simply preventing the loss of water but also, include generating a stress response, increasing BP, stimulating protein synthesis, stimulating fat accumulation, and maintaining elevated serum glucose (insulin resistance) to provide energy to the brain. ACTH, adrenocorticotrophic hormone; CNS, central nervous system; RAS, renin angiotensin system.

Figure 2.

Potential mechanisms involved in heat stress–associated CKD. CKD occurring in response to recurrent dehydration may involve a variety of mechanisms. Central to the loss of water is the development of hyperosmolarity, which stimulates the release of vasopressin, and the generation of fructose in the kidney from activation of the polyol (aldose reductase-sorbitol dehydrogenase) pathway. Vasopressin acts to increase glomerular hydrostatic pressure and increases the risk for progression of kidney disease.^,, Endogenous fructose production is also metabolized by fructokinase in the proximal tubule, resulting in tubular injury and the release of oxidants, uric acid, and chemokines. Fructose may also increase vasopressin levels, and likewise, rehydration with sugar beverages may provide additional fructose, with an amplification of the vasopressin and uric acid levels. Furthermore, other factors that may be involved include low–grade muscle injury associated with excessive physical exertion leading to subclinical rhabdomyolysis, an increased risk for nonsteroidal anti–inflammatory drug (NSAID) use, and rarely, hypotension from volume depletion. Volume depletion may also be associated with activation of the renin-angiotensin system and development of hypokalemia, which may also play a role in kidney disease.

Figure 3.

Modern diseases engaged by water shortage and global climate change. Although the vasopressin system was developed as a survival mechanism when the host lost either intracellular or extracellular volume, in modern society, it may, instead, be associated with the development of diseases. Climate change and water shortage triggered with diets high in fructose (sugar), salt, and umami foods may lead to overactivation of this pathway. The metabolic effects of high osmolarity may include the syndrome of obesity, metabolic syndrome, and diabetes. In contrast, recurrent dehydration and highly concentrated and acidic urine may increase the risk for crystallization of uric acid and chronic kidney damage.