Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate

Abstract

Background: Heat stress and rhabdomyolysis are major risk factors for the occurrence of repeated acute kidney injury in workers exposed to heat and strenuous work. These episodes, in turn, may progress to chronic kidney disease. Objective: The purpose of this study was to test the effect of allopurinol (AP) and sodium bicarbonate on the kidney injury induced by recurrent heat stress dehydration with concomitant repeated episodes of rhabdomyolysis. Methods: The model consisted of heat stress exposure (1 h, 37°C) plus rhabdomyolysis (R) induced by repetitive IM injections of glycerol (7.5 mL/kg BW days) in the rat. In addition, to replicate the human situation, uricase was inhibited (oxonic acid [OA] 750 mg/K/d) to increase uric acid (UA) levels. Additional groups were treated either with AP 150 mg/L, n = 10, bicarbonate (BC; 160 mM, n = 10), or both (AP + BC, n = 10) in drinking water. We also included 2 control groups consisting of normal controls (N-Ref, n = 5) and uricase-inhibited rats (OA, n = 5) that were not exposed to heat or muscle injury. Groups were studied for 35 days. Results: Uricase-inhibited rats exposed to heat and rhabdomyolysis developed pathway and increased intrarenal oxidative stress and inflammasome activation. Kidney injury could be largely prevented by AP, and also BC, although the treatments were not synergistic. Conclusion: Increased levels of UA may play an important role in the renal alterations induced by heat stress and continuous episodes of rhabdomyolysis. Therefore, treatments aimed to reduce hyperuricemia may help to decrease the renal burden in these conditions. Clinical trials are suggested to test whether this is also true in humans.

Renoprotective effect of oral rehydration solution III in exertional heatstroke rats

“…Finally, sodium citrate, a component in ORS III, is also an effective bicarbonate analog after being metabolized. Since bicarbonate has proved to prevent kidney injury through lowering uric acid levels in heatstroke [31,32], citrate may play a role in preventing AKI. ORS III is crucial to and will benefit EHS rats.…”

<p>Purposeful Review to Identify Risk Factors, Epidemiology, Clinical Features, Treatment and Prevention of Chronic Kidney Disease of Unknown Etiology</p>

“…99,100 In addition, according to some studies, sodium bicarbonate delays the progression of CKD 96,101 and one experimental study has demonstrated its protective role in preventing kidney injury from repeated heat stress. 102…”

The Potential for Renal Injury Elicited by Physical Work in the Heat

“…This is supported by human data demonstrating that the presence of muscle damage increases the risk of AKI during exercise in the heat [36]. These data were recently corroborated in a rodent model of repeated heat exposure, which demonstrated that experimental rhabdomyolysis worsened heat-induced kidney injury [37]. That said, epidemiological data obtained from Guatemalan sugarcane workers indicate that the presence of rhabdomyolysis is not associated with cross-shift declines in kidney function [26], suggesting that the contribution of rhabdomyolysis to progressive reductions in kidney function in this population is likely small.…”