Acute kidney injury biomarker responses in young and older female adults following mild hypohydration

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). In a random crossover design, 17 YF (20-35 yr old) and 9 OF (55-75 yr old), who were apparently healthy, completed two hydration protocols with ≥1 wk washout: 1) baseline hydration, and 2) stepwise water restriction over 3 days, concluding with 16 h water deprivation. We assessed hydration, AKI biomarkers, and the renin-angiotensin-aldosterone system (RAAS) from blood and 24-h urine samples. The effects of age group and condition were assessed using two-way mixed-effects analysis and reported as means ± SD. 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 in OF (P = 0.69), with a significant interaction effect (P = 0.017). Nephrin excretion and product of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinase-2 (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. 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.NEW & NOTEWORTHY This is the first study to assess the effects of mild hypohydration on acute kidney injury biomarkers in young and older female adults. Mild hypohydration altered acute kidney injury biomarker concentrations in both age groups, with no observed age-related differences, contrasting with male studies that show an age-related decline. These findings highlight the need for targeted research on potential sex-related differences in kidney function decline with aging.