title: Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.
abstract: Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention.
authors.affiliation: Division of Kidney Diseases and Hypertension, University of Colorado, Denver, CO.
authors.forename: Carlos
authors.initials: C
authors.lastname: Roncal-Jimenez
authors.affiliation: Scientific Board, Department of Investigation, Hospital Nacional Rosales, San Salvador, El Salvador.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Trabanino
authors.affiliation: Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Barregard
authors.affiliation: Division of Kidney Diseases and Hypertension, University of Colorado, Denver, CO.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.affiliation: Unit of Occupational Medicine, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Catharina
authors.initials: C
authors.lastname: Wesseling
authors.affiliation: Division of Kidney Diseases and Hypertension, University of Colorado, Denver, CO.
authors.forename: Tamara
authors.initials: T
authors.lastname: Harra
authors.affiliation: Research Center on Health, Work and Environment (CISTA), National Autonomous University of Nicaragua at León (UNAN-León), León, Nicaragua.
authors.forename: Aurora
authors.initials: A
authors.lastname: Aragón
authors.affiliation: University of Balearic Islands, Palma de Mallorca, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Grases
authors.affiliation: Agencia para el Desarrollo y la Salud Agropecuaria, San Salvador, El Salvador.
authors.forename: Emmanuel R
authors.initials: ER
authors.lastname: Jarquin
authors.affiliation: Research Center on Health, Work and Environment (CISTA), National Autonomous University of Nicaragua at León (UNAN-León), León, Nicaragua; Department of Non-communicable Disease Epidemiology of London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: González
authors.affiliation: La Isla Foundation, San Salvador, El Salvador.
authors.forename: Ilana
authors.initials: I
authors.lastname: Weiss
authors.affiliation: La Isla Foundation, San Salvador, El Salvador.
authors.forename: Jason
authors.initials: J
authors.lastname: Glaser
authors.affiliation: Laboratory of Renal Physiopathology and Nephrology Department, INC Ignacio Chavez, Mexico City, Mexico.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.affiliation: Division of Kidney Diseases and Hypertension, University of Colorado, Denver, CO; Division of Nephrology, Eastern Colorado Health Care System, Department of Veteran Affairs, Denver, CO. Electronic address: richard.johnson@ucdenver.edu.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000328:Adult; D002489:Central America; D003460:Crystallization; D015444:Exercise; D018882:Heat Stress Disorders / Q000209:etiology*; D006801:Humans; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000209:etiology*; D014527:Uric Acid / Q000652:urine*
chemical_list: D014527:Uric Acid
keywords: Central America; Mesoamerican nephropathy (MeN); chronic kidney disease (CKD); dehydration; etiology; heat stress nephropathy; hyperuricemia; hypothesis; physical exertion; rhabdomyolysis; sugarcane workers; tubular injury; uric acid crystalluria; uric acid disorder; uricosuria; urinary acidification