FIG 4.

Comparison of urinary injury biomarkers for rats in the variable vancomycin dose arm, between treatment groups and across dosing days. The folic acid group (AKI positive control) was used as the comparator. (a) Among rats in the low-VAN group, significant differences in urinary KIM-1 were observed on day 1 (a, −215.6 ng/24 h [95% CI, −365.6 to −65.6 ng/24 h] [P = 0.005]), day 2 (b, −344.1 ng/24 h [95% CI, −494.1 to −194.1 ng/24 h] [P < 0.001]), day 3 (c, −239.4 ng/24 h [95% CI, −389.4 to −89.3 ng/24 h] [P = 0.002]), and day 4 (d, −154.3 ng/24 h [95% CI, −304.3 to −4.24 ng/24 h] [P = 0.044]). Among rats in the high-VAN group, significant differences in urinary KIM-1 were observed on day 3 (e, −154.4 ng/24 h [95% CI, −304.4 to −4.33 ng/24 h] [P = 0.044]). (b) Among rats in the low-VAN group, the urinary clusterin was significantly lower on day 2 (f, −20,652 ng/24 h [95% CI, −34,917 to −6,388 ng/24 h] [P = 0.005]) and day 4 (g, −15,682 ng/24 h [95% CI, −29,947 to −1,418 ng/24 h] [P = 0.031]). Among rats in the high-VAN group, the urinary clusterin was significantly lower on day 4 (h, −17,866 ng/24 h [95% CI, −32,131 to −3,602 ng/24 h] [P = 0.014]). (c) Among rats in the low-VAN group, the urinary OPN was significantly lower on day 1 (k, −38.5 ng/24 h [95% CI, −54.7 to −22.2 ng/24 h] [P < 0.001]), day 2 (m, −52.1 ng/24 h [95% CI, −68.4 to −35.8 ng/24 h] [P < 0.001]), day 3 (n, −33.9 ng/24 h [95% CI, −51.1 to −16.7 ng/24 h] [P < 0.001]), and day 4 (p, −57.6 ng/24 h [95% CI, −73.2 to −42.0 ng/24 h] [P < 0.001]). Among rats in the high-VAN group, the urinary OPN was significantly lower on day 1 (q, −37.0 ng/24 h [95% CI, −52.6 to −21.4 ng/24 h] [P < 0.001]), day 2 (r, −48.6 ng/24 h [95% CI, −64.2 to −33.0 ng/24 h] [P < 0.001]), day 3 (s, −37.0 ng/24 h [95% CI, −52.6 to −21.4 ng/24 h] [P < 0.001]), and day 4 (t, −60.2 ng/24 h [95% CI, −78.8 to −41.6 ng/24 h] [P < 0.001]).