Water intake mediates cross-sectional associations between urinary kidney injury biomarkers and race in emerging adults.

Experimental hypohydration increases acute kidney injury (AKI) biomarkers, indicating potential kidney stress. Black adults are more likely to be underhydrated than White adults, yet it is unclear whether habitual hydration is associated with AKI biomarkers or whether racial differences exist, particularly in emerging adults. Fifty-four participants (24 Black/30 White, 27 M/27 F, age: 21 ± 1 yr, mean ± SD) provided diet diaries to assess water intake and 24-h urine samples. We assessed hydration biomarkers [urine osmolality, urine specific gravity (USG)], creatinine clearance, and urinary AKI biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), thioredoxin-1 (TRX-1), tissue inhibitor of metalloproteinase 2 (TIMP-2), insulin-like growth factor binding protein 7 (IGFBP7), and TIMP-2 × IGFBP7. Black adults exhibited higher USG (P = 0.043) and urine osmolality [534(506) vs. 303(541) mosmol/kgH2O, P = 0.007, median (IQR)], and reported lower water intake (P < 0.001), but there was no difference in creatinine clearance (P = 0.250) compared with White adults. Black adults exhibited higher urinary NGAL, TIMP-2, IGFBP7, and TIMP-2 × IGFBP7 (ps ≤ 0.034) concentrations, but not urinary KIM-1 or TRX-1 (ps ≥ 0.096) concentrations. When indexed to urine flow rate, the racial difference persisted only for TIMP-2 × IGFBP7 [319(467) vs. 215(214) [ng/mL]2/min, P = 0.014]. In a regression model with sex, urine osmolality, and water intake (R2 = 0.596, P < 0.001), race was no longer associated with TIMP-2 × IGFBP7 (P = 0.168). Mediation analysis revealed that water intake mediated 82.6% (P = 0.007) of the race difference in TIMP-2 × IGFBP7 (overall P = 0.015). Racial disparities in urinary TIMP-2 × IGFBP7 excretion between emerging Black and White adults may be mediated by water intake differences.NEW & NOTEWORTHY Apparently healthy emerging Black adults exhibited higher concentrations of several kidney injury biomarkers, collected via a 24-h urine sample, compared with White adults. Racial group differences in all kidney injury biomarkers tested, except for TIMP-2 × IGFBP7 (the only FDA-approved urinary kidney injury biomarker), were attenuated once indexed to urinary hydration markers. Water intake mediated the racial group difference in TIMP-2 × IGFBP7. Future work is needed to determine whether hydration interventions could mitigate racial differences in TIMP-2 × IGFBP7.