|
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. |
|