Molecular Challenges and Opportunities in Climate Change-Induced Kidney Diseases

Abstract

As temperatures continue to modify due to weather changes, more regions are being exposed to extreme heat and cold. Physiological distress due to low and high temperatures can affect the heart, blood vessels, liver, and especially, the kidneys. Dehydration causes impaired cell function and heat itself triggers cellular stress. The decline in circulating plasma volume by sweat, which stresses the renal and cardiovascular systems, has been related to some molecules that are crucial players in preventing or provoking cellular damage. Hypovolemia and blood redistribution to cutaneous blood vessels reduce perfusion to the kidney triggering the activation of the renin-angiotensin-aldosterone system. In this review, we expose a deeper understanding of the modulation of molecules that interact with other proteins in humans to provide significant findings in the context of extreme heat and cold environments and renal damage reversal. We focus on the molecular changes exerted by temperature and dehydration in the renal system as both parameters are heavily implicated by weather change (e.g., vasopressin-induced fructose uptake, fructogenesis, and hypertension). We also discuss the compensatory mechanisms activated under extreme temperatures that can exert further kidney injury. To finalize, we place special emphasis on the renal mechanisms of protection against temperature extremes, focusing on two important protein groups: heat shock proteins and sirtuins.

Keywords: RAAS; chronic kidney disease; fructose uptake; heat shock proteins; heat stress; molecular mechanisms; public health; sirtuins; therapeutic.

Figure 1

Compensatory mechanisms associated with extreme temperatures and their detrimental chronic effects on tubular and glomerular cells. Abbreviations: AR: aldose reductase; ATP: adenosine triphosphate; H₂O: water; NF-kB: nuclear factor kappa-beta; ROS: reactive oxygen species; the brackets [] flanking a substance refer to the concept “concentration” of the substances inside it. Upregulated enzymes in the metabolic shift produced by vasopressin are marked with red rectangles.

Figure 2

Acute compensatory response elicited by sirtuins against heat-induced stress. Abbreviations: ADH: antidiuretic hormone; AQP-2: aquaporin 2; BP: blood pressure; IL: interleukin; MMP: metalloproteinase; NE: norepinephrine; SIRT: sirtuins; V1: V1 receptor; V2: V2 receptor. Green arrows indicate induction, while red arrows indicate inhibition. Upward arrows indicate upregulation, while downward arrows indicate downregulation.

Figure 3

Chronic compensatory response elicited by sirtuins against heat-induced stress. Abbreviations: AGE’s: advanced glycation end products; BAT: brown adipose tissue; CKD: chronic kidney disease; ET-1: endothelin-1; HIF-1α: hypoxia inducible factor 1-alpha; IL: interleukin; RAAS: renin–angiotensin–aldosterone axis; ROS: reactive oxygen species; SIRT: sirtuins; TNF-α: tumor necrosis factor-alpha; UCP-1: uncoupling protein-1; VEGF: vascular endothelial growth factor. Green arrows indicate induction, while red arrows indicate inhibition.