Serum biomarker  
    BUN
(mg/dL)
Cr
(mg/dL)
Cr*
(mg/dL)
TP§*
(mg/mg)
MAlb§*
(ng/mg)
Alb§*
(mg/mg)
Lpn2§
(mg/mg)
KIM-1§*
(mg/mg)
Opn§
(mg/mg)
Nephron specificity N-S N-S N-S G, PT G, PT G, PT G, PT
DT
PT G, PT, DT, LH
Animal # Severity ScoreΣ
1 0 7 0.4 29.7 0.3 0.00 12744 170.6 0.9 3.9
2 0 10 0.4 20.7 0.6 0.00 10131 236.2 1.3 9.4
3 0 12 0.5 44.7 0.6 0.04 15510 318.4 0.8 5.3
4 0 12 0.4 31.9 0.5 0.00 9748 181.7 1.1 5.0
5 1 11 0.5 40.5 0.5 0.00 8619 193.2 1.0 7.2
21 5 9 0.4 50.1 0.7 1.20 105858 370.3 0.5 5.0
22 6 12 0.4 31.3 0.8 3.19 108817 280.8 0.5 5.1
23 4 11 0.3 68.2 0.4 1.47 38808 246.6 0.5 5.7
24 6 12 0.5 82.6 1.4 2.42 107431 231.7 0.6 4.8
25 5 12 0.5 66.4 2.8 9.04 126500 269.5 0.4 7.0
AUROC 0.62 0.44 0.88 0.84 1.00 1.00 0.80 1.00 0.42
AUC P value  0.65 0.83 0.09 0.15 0.009 0.009 0.22 0.009 0.77
On study days 1 and 8, male Sprague-Dawley rats were administered via a lateral tail vein a bolus intravenous injection of either doxorubicinor saline. Study termination was on day 14.§Urinary protein biomarker concentrations were normalized to concurrent urinary creatinine (uCr) concentrations on day 7.*Doxorubicin related increased urinary protein biomarker concentrations exhibited predictive power for early, non-invasive prediction of progressive glomerular toxicity with secondary renal tubular reabsorption impairment. §Doxorubicin-induced increased urinary albumin(uAlb) concentrations were above the upper limit of assay detection. SValues represent the sum of the individual animal histopathology severity scores. AUROC represented biomarker performance according to the following scale: ≥0.90 (high), 0.80-0.90 (moderate), 0.70-0.80 (mild) and ≤0.60 (poor).The P value represents the probability of rejecting the null hypothesis that the AUROC curve is 0.5, indicating that there is no predictive power at all. Other abbreviations: blood urea nitrogen BUN; total protein, TP; microalbumin, MAlb; lipocalin-2, Lpn2; kidney injury molecule 1, KIM-1; osteopontin, Opn.
Table 7: Biomarker performance in the prediction of subclinical doxorubicin related nephrotoxicity.