Prolonged Mild Hypohydration Increases Acute Kidney Injury Biomarkers In Healthy Young Males And Females

The top causes of hospitalizations during extreme heat events are fluid and/or electrolyte disorders, and acute kidney injury (AKI) which typically is a secondary consequence of hypohydration. Inadequate fluid intake may cause hypohydration during normal daily living prior to extreme heat exposure. In this scenario, people are likely mildly hypohydrated (approximate 2% body mass loss). In the context of extreme heat, 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) separated by ≥72 hours. Body fluid losses were estimated via percent change in nude body mass over the 24-hour protocol. Spot urine samples were collected 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), P < 0.0001]. HYPO caused marked increases in urinary [IGFBP7·TIMP-2] [1.9 (ng/ml)2/1000 (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 < 0.0001] compared to EUHY. Urinary NGAL was not different between conditions [HYPO: 0.7 ng/ml (0.3, 1.1); EUHY: 0.8 ng/ml (0.3, 1.3), P = 0.7524]. CONCLUSION: These data indicate that prolonged mild hypohydration increases biomarkers associated with potential renal tubular epithelial cell injury that are suggestive of increased AKI risk. Funded by NIH R01HL144128 and F32HL164021, and Wu Tsai Human Performance Alliance.