Renin-Angiotensin-Aldosterone System and Acute Kidney Injury Markers After Mild Dehydration in Young and Older Female Adults

Purpose: Past studies demonstrate that aging reduces kidney function and increases dehydration risk, potentially exacerbating kidney injury risk. However, most research in this area was conducted in males. Therefore, we tested the hypothesis that female aging also attenuates the renin-angiotensin-aldosterone system (RAAS) suppression and augments increases in acute kidney injury biomarkers after water deprivation (WD). Methods: 17 young and 9 older females (Y: 24±4 vs. O: 66±6 years), all generally healthy, completed two trials in random crossover fashion ≥1 week apart. We sampled blood in the laboratory after 3 days of euhydration (CON) and after 3 days of gradually reduced water intake concluded with a 16-h WD period. Participants were instructed to consume the recommended dietary guidelines of 2,300 mg of sodium daily for each condition. Urine was collected during the last 24 hours of each condition and used for indexing urinary acute kidney injury markers to flow rate. Osmolality was measured using freezing point depression. Circulating aldosterone and angiotensin 2 were analyzed using radioimmunoassays. Plasma renin activity and urinary neutrophil gelatinase-associated lipocalin (NGAL), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase-2 (TIMP-2), and nephrin were measured using enzyme-linked immunosorbent assays. We analyzed data using two-way mixed models (condition x age group) and reported differences (∆; WD-CON) as mean±SD or median[IQR]. Results: WD raised 24-hr urine osmolality (Young: ∆220±91 vs. Older: ∆233±108 mOsm/kg; condition: p<0.001) with no age or interaction effects (p≥0.96). Irrespective of condition, older adults exhibited ~10 mOsm/kg higher plasma osmolality (age: p<0.001), which increased after WD (Y: ∆3±3 vs. O: ∆3±4 mOsm/kg; condition: p=0.001) with no interaction effect (p=0.95). Older adults exhibited ~0.8 ng/ml/hr lower (age: p=0.046) plasma renin activity (Y: ∆-0.12[1.44] vs. O: ∆-0.02[0.18] ng/ml/hr) with no condition or interaction effects (p≥0.83). There were no main or interaction effects (age: p=0.053; condition and interaction: p≥0.61) for plasma angiotensin 2 (Y: ∆-1.7[4.8] vs. O: ∆-0.2[15.2] pg/ml) or serum aldosterone (Y: ∆-1.6±3.5 vs. O: ∆0.1±1.3 ng/dl; all effects: p≥0.29). There were no main or interaction effects (age and interaction: p≥0.69; condition: p=0.06) for NGAL (Y: ∆-1.9[7.8] vs. O: ∆-1.2[5.5] ng/min). The product of IGFBP7 and TIMP-2 (Y: ∆0.4[0.3] vs. O: ∆0.5[0.4] (ng/mL) 2 /1000/min) increased significantly from WD (condition: p<0.001) without significant age or interaction effects (p≥0.40). Similarly, WD raised nephrin significantly (Y: ∆44[47] vs. O: ∆39[33] ng/min; condition: p<0.001) without significant age (p=0.07) or interaction effects (p=0.68). Conclusion: These findings suggest that female aging does not significantly alter RAAS and kidney injury marker responses to mild dehydration. Our findings contrast with studies in males, where aging impacts dehydration responses more profoundly, and highlight the importance of assessing differences between sexes when examining how aging affects the RAAS and acute kidney injury markers. FSU Graduate School Legacy Fellowship (CD); NIH K01HL147998 (ATR), K01HL164978 (MCB), & K01HL160772 (JCW); AHA 23CDA1037938 (JCW); FSU ISL (KAS & JCW). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.