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Kidney Injury from Recurrent Heat Stress and Rhabdomyolysis: Protective Role of Allopurinol and Sodium Bicarbonate.
- Source :
-
American journal of nephrology [Am J Nephrol] 2018; Vol. 48 (5), pp. 339-348. Date of Electronic Publication: 2018 Nov 02. - Publication Year :
- 2018
-
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.<br />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.<br />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.<br />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.<br />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.<br /> (© 2018 S. Karger AG, Basel.)
- Subjects :
- Acute Kidney Injury etiology
Acute Kidney Injury pathology
Animals
Disease Models, Animal
Disease Progression
Glycerol administration & dosage
Glycerol toxicity
Hot Temperature adverse effects
Humans
Kidney drug effects
Kidney pathology
Male
Occupational Exposure adverse effects
Oxidative Stress drug effects
Oxonic Acid administration & dosage
Rats
Renal Insufficiency, Chronic etiology
Renal Insufficiency, Chronic pathology
Renal Insufficiency, Chronic prevention & control
Rhabdomyolysis blood
Rhabdomyolysis etiology
Treatment Outcome
Urate Oxidase antagonists & inhibitors
Urate Oxidase metabolism
Uric Acid blood
Uric Acid metabolism
Acute Kidney Injury drug therapy
Allopurinol administration & dosage
Heat-Shock Response
Rhabdomyolysis drug therapy
Sodium Bicarbonate adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9670
- Volume :
- 48
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 30391956
- Full Text :
- https://doi.org/10.1159/000494663