Hydration mediates cross-sectional associations between acute kidney injury biomarkers and race in emerging adults

Background: Chronic underhydration is associated with chronic kidney disease (CKD). Acute kidney injury (AKI) events can initiate and accelerate CKD. Short-term experimental hypohydration increases urinary AKI biomarkers. Black adults are more likely than White adults to be underhydrated and to develop end-stage CKD. However, it remains unclear whether habitual hydration is associated with AKI biomarkers, and whether there are racial differences in AKI biomarkers. Therefore, we sought to examine AKI biomarkers and habitual hydration status in emerging Black and White adults. Methods: Fifty-four participants (24 Black/30 White, 27 M/27 F, age 21 ± 1 y, BMI: 26 ± 4 kg/m 2 , mean ± SD) provided 3-day food and fluid diaries to assess water intake and collected 24-hour urine samples, which were analyzed for hydration biomarkers (urine osmolality, urine specific gravity (USG)), urine flow rate, and creatinine. Creatinine clearance, derived from serum and 24-hour urine creatinine, served as a proxy for kidney function. We used a panel of urinary AKI biomarkers, including Kidney Injury Molecule 1 (KIM-1), Neutrophil Gelatinase–Associated Lipocalin (NGAL), Thioredoxin-1 (TRX-1), Tissue Inhibitor of Metalloproteinases 2 (TIMP2), Insulin-like Growth Factor Binding Protein 7 (IGFBP7), and their product, TIMP2*IGFBP7, an FDA-approved biomarker for assessing clinical AKI risk. All AKI biomarkers were indexed to urine flow rate. Independent t-tests and Mann-Whitney U-tests were used to assess racial group differences. TIMP2*IGFBP7 was log-transformed, and hierarchical regression and mediation models were used to determine whether hydration mediates potential racial group differences in AKI biomarkers (α ≤ 0.05). Results: Black adults exhibited higher USG (p=0.043) and urine osmolality (534(506) vs. 303(541), p=0.007, median(IQR)), lower water intake normalized to body surface area (12.40±3.27 vs. 18.60±5.70 ((g/m2)/100), p< 0.001), and no difference in creatinine clearance (p=0.250) compared with White adults. Black adults exhibited higher urinary NGAL (p=0.002), TIMP2 (p=0.034), IGFBP7 (p< 0.001), and TIMP2*IGFBP7 (p=0.011) concentrations. There were no differences in urinary KIM-1 (p=0.332) and TRX-1 (p=0.096) concentrations between racial groups. When indexed to urine flow rate, the racial difference persists only in TIMP2*IGFBP7 (Black adults: 319(467) vs. White adults: 215(214) [ng/mL]2/min, p=0.014). In a regression model with sex, race, urine osmolality, and normalized water intake (R2=0.596, p< 0.001), race was no longer associated with flow rate-indexed TIMP2*IGFBP7 (p=0.168), however, urine osmolality was (β=0.576, p< 0.001). Mediation analysis revealed that normalized water intake mediated 82.6% (indirect mediation effect: p=0.007) of the effect of race on TIMP2*IGFBP7 (overall model p=0.021). Conclusion: Our data indicate that racial differences in TIMP2*IGFBP7 between healthy emerging Black and White adults are largely mediated by hydration status, suggesting habitual underhydration may contribute to racial disparities in renal stress. This abstract was presented at the American Physiology Summit 2026 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.