Acute Kidney Injury Biomarker Responses in Young and Older Female Adults Following Mild Hypohydration.

Background: Hypohydration reduces kidney function and increases acute kidney injury (AKI) risk. Aging increases hypohydration-induced kidney dysfunction in males, but female aging studies are lacking. Therefore, we compared the effects of mild hypohydration on kidney function and AKI biomarkers in young (YF) and older female adults (OF). Methods: In a random crossover design, seventeen YF (20-35 years old) and 9 OF (55-75 years old), who were apparently healthy, completed two hydration protocols with ≥1 week washout: 1) baseline hydration, and 2) stepwise water restriction over 3 days, concluding with 16 hours water deprivation. We assessed hydration, AKI biomarkers, and the renin-angiotensin-aldosterone system (RAAS) from blood and 24-hour urine samples. The effects of age group and condition were assessed using two-way mixed-effects analysis and reported as mean±SD. Results: Hypohydration increased urine specific gravity and osmolality (condition effect: p<0.001) with no other main effects. Neutrophil gelatinase-associated lipocalin excretion decreased with hypohydration (p=0.04), independent of age (p=0.62). Urine cystatin C excretion increased in YF (p<0.001) but not OF (p=0.69), with a significant interaction effect (p=0.017). Nephrin excretion and urinary IGFBP7*TIMP-2 increased after hypohydration (both p<0.001), independent of age (both p≥0.35). OF exhibited lower plasma renin activity than YF (p=0.046), with no other main or interaction effects for other RAAS markers. Conclusions: OF did not exhibit greater AKI biomarker responses to mild hypohydration, contrasting with male studies showing age-related kidney function decline. These results highlight the need for research to clarify potential sex-based differences in age-related decline in kidney function.