Hyperthermia and Dehydration During Physical Work in the Heat Both Contribute to the Risk of Acute Kidney Injury
Authors: Chapman Christopher L. , Johnson Blair D. , Vargas Nicole T. , Hostler David , Parker Mark D. , Schlader Zachary J. 
Published: April 2020

Occupational heat stress increases the risk of acute kidney injury (AKI) and kidney disease. Rodent models indicate that the extent of renal damage is dependent on the magnitude of hyperthermia (i.e., increase in core temperature) and/or dehydration incurred during heat stress, but the mechanism (heat vs hydration) remains unclear. The risk of AKI can be assessed using a panel of AKI biomarkers.PurposeTest the hypothesis that attenuating the magnitude of hyperthermia and/or dehydration during prolonged physical work in the heat reduces the risk of AKI.MethodsThirteen healthy adults (23±2 y, 3 females) exercised for 2 h in a 39.7 ± 0.6°C, 32 ± 3% relative humidity environment. In four quasi‐randomized trials, subjects received: water to remain euhydrated (W), continuous upper body cooling via a tube‐lined suit top perfusing 2°C water (C), a combination of both water and cooling (WC), or no intervention (CON). Blood and urine samples were collected immediately before exercise (Pre), after exercise (Post), and 80 minutes after the end of the exercise protocol (Recovery). A panel of biomarkers in the blood and urine were used to assess the risk of AKI for the given condition, with greater increases in biomarkers interpreted as a relatively higher risk of AKI. Elevations in urine albumin were interpreted as greater glomerular permeability and reduced renal tubular reabsorption of albumin. Neutrophil gelatinase‐associated lipocalin (NGAL) was measured in the plasma as an indicator of renal ischemia and in the urine to assess general tubular injury. The cell cycle arrest markers insulin‐like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase 2 (TIMP‐2) were measured in the urine to assess renal epithelial damage in the proximal (IGFBP7) and distal (TIMP‐2) tubule cells. Data were analyzed as the change from Pre (Δ) and are presented as mean ± SD.ResultsThe magnitude of hyperthermia (intestinal temperature) was greatest in CON (CON: 1.9 ± 0.3; W: 1.2 ± 4.4; C: 1.1 ± 0.4; WC: 0.8 ± 0.3°C, P<0.01). At the end of the exercise, dehydration (percent loss of body mass) was greatest in CON (CON: −2.4 ± 0.5; W: −0.2 ± 0.4; C: −1.5 ± 0.3; WC: 0.1 ± 0.4%, P<0.01). At Post, increases in plasma NGAL were greater in CON (20 ± 13 ng/dL, P≤0.04) compared to the other trials (W: 7 ± 11; C: 10 ± 9; WC: 9 ± 10 ng/dL). At Recovery, there were greater increases in CON compared to all other trials for albumin (CON: 13 ± 11; W: 3 ± 4; C: 5 ± 8; WC: 2 ± 2 μg/mL, P≤0.05) and IGFBP7 (CON: 227 ± 190; W: 44 ± 62; C: 102 ± 52; WC: 33 ± 29 ng/mL, P≤0.05). Increases in urine NGAL at Recovery were greater in CON compared to W and WC (CON: 16 ± 14; C: 7 ± 6; WC: 7 ± 10 ng/dL, P≤0.05). There were no differences in increases in TIMP‐2 between trials (P≥0.11). Greater increases in IGFBP7 from Pre in CON persisted after correcting for urine production and concentration.ConclusionThe risk of AKI is highest with greater magnitudes of hyperthermia and dehydration during physical work in the heat. Additionally, the differential findings between IGFBP7 and TIMP‐2 suggest the proximal tubules as the likely site of potential renal injury.Support or Funding InformationCarl V. Gisolfi Memorial Fund from the ACSM (#17‐00580), the MDRF from the University at Buffalo (#SP‐19‐04), and the U.S. CDC (R01OH011528).