Acute Kidney Injury Biomarkers and Hydration Assessments Following Prolonged Mild Hypohydration in Healthy Young Adults.

The high prevalence of inadequate hydration (e.g., hypohydration, underhydration) is concerning given that extreme heat increases excess hospitalizations for fluid/electrolyte disorders and acute kidney injury (AKI). Inadequate hydration may also be related to renal and cardiometabolic disease development. This study tested the hypothesis that prolonged mild hypohydration increases the urinary AKI biomarker [IGFBP7∙TIMP-2] (product of insulin-like growth factor binding-protein 7 and tissue inhibitor of metalloproteinase-2) compared to euhydration. Additionally, we determined the diagnostic accuracy and optimal cut-offs of hydration assessments for discriminating positive AKI risk ([IGFBP∙TIMP-2] >0.3 ng∙ml)∙1000). In a block-randomized crossover design, twenty-two healthy young adults (11 females, 11 males) completed 24 h of fluid deprivation (Hypohydrated) or 24 h normal fluid consumption (Euhydrated) separated by ≥72 h. Urinary [IGFBP7∙TIMP-2] and other AKI biomarkers were measured following the 24-h protocols. Diagnostic accuracy was assessed via receiver operating characteristic curve analysis. Urinary [IGFBP7∙TIMP-2] [1.9 (95% CI: 1.0-2.8) vs. 0.2 (95% CI: 0.1-0.3) (ng∙ml)∙1000, P=0.0011] was markedly increased in Hypohydrated vs. Euhydrated. Urine osmolality [AUC: 0.91, P<0.0001] and urine specific gravity [AUC: 0.89, P<0.0001] had the highest overall performance for discriminating positive AKI risk. Optimal cut-offs with positive likelihood ratio of 11.8 for both urine osmolality and specific gravity were 952 mOsm/kg and 1.025 a.u. In conclusion, prolonged mild hypohydration increased urinary [IGFBP7∙TIMP-2] in males and females. Urinary [IGFBP7∙TIMP-2] corrected to urine concentration was elevated in males only. Urine osmolality and urine specific gravity may have clinical utility for discriminating positive AKI risk following prolonged mild hypohydration.