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PROLONGED MILD HYPOHYDRATION INCREASES ACUTE KIDNEY INJURY BIOMARKERS IN HEALTHY YOUNG MALES AND FEMALES

Abstract

S.M. Holt, C.L. Chapman, W.A.B. Howells, C.T. O’Connell, S.C. Brazelton, H.N. Medved, E.L. Reed, K. Wiedenfeld Needham, J.R. Halliwill, FACSM, C.T. Minson, FACSM

University of Oregon, Eugene, OR

(Award Winner)

The top causes of hospitalizations during extreme heat events are fluid and/or electrolyte disorders, and acute kidney injury (AKI) secondary to hypohydration. Prior to extreme heat exposure, people are likely mildly hypohydrated (approximate 2% body mass loss) during normal daily living due to inadequate fluid intake. In this context, an important knowledge gap exists as to whether mild hypohydration independent of heat stress increases AKI biomarkers that are suggestive of increased AKI risk. PURPOSE: To test the hypothesis that urinary AKI biomarkers are elevated in humans following prolonged mild hypohydration compared to euhydration. METHODS: In a block-randomized crossover design, twenty-two healthy adults [11 females, 11 males; 21(3) years; body mass index: 23(3) kg/m2] completed 24 hours of fluid deprivation (HYPO) or 24 hours normal fluid consumption (EUHY). Protocols were separated by ³72 hours. Body fluid losses were estimated via the percent change in nude body mass over the 24-hour protocol. Spot urine samples were collected from participants immediately following the 24-hour protocol. Urinary AKI biomarkers insulin-like growth factor binding-protein 7 (IGFBP7), tissue inhibitor of metalloproteinase-2 (TIMP-2), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase associated lipocalin (NGAL) were measured with enzyme-linked immunosorbent assays. The primary dependent variable was the U.S. Food and Drug Administration approved biomarker urinary ([IGFBP7∙TIMP-2]). Data are presented as mean with 95% confidence intervals. RESULTS: Body mass loss was greater in HYPO vs. EUHY [-2.5% (-2.9, -2.1) vs. 0.0% (-0.4, 0.4), P2/1000 (1.0, 2.8) vs. 0.2 (ng/ml)2/1000 (0.1, 0.3), P=0.0011] and KIM-1 [1.0 ng/ml (0.8, 1.3) vs. 0.3 ng/ml (0.2, 0.4) P

Supported by NIH R01HL144128 and F32HL164021, and the Knight Campus Undergraduate Scholars Program.

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