Abstract

Cisplatin (Cp) is extensively utilized as an antineoplastic drug employed in the treatment of
miscellaneous solid tumors with serious side effects such as nephrotoxicity. Therefore, traditional
biomarkers including urinary creatinine (uCr) and serum creatinine (sCr) are utilized for detection
of Cp-induced renal injury. In this study, we compared changes in uCr/uCr gene expression levels
(ml/min) at 1 ,2and 4 h and 2, 3, 4, 7,10,14 and 28 days after cisplatin infusion (0.75 mg/mL) versus
baseline in 7 consecutive patients of solid kidney tumors with chronic kidney injury(CKI) and 3
consecutive controls without CKI. Furthermore, short-term cisplatin chemotherapy (STC, 1 day)
was compared to long-term (LTC, 28days) treatment using plasma and urine creatinine and renal
histology. We found CKI was associated with higher levels of sCr (149.5± 19.08versus 124 ±
23.54ng/mL, P < 0.001) and uCr (0.66± 0.11versus 0.94± 0.05, P < 0.001) compared with exposed
controls. Patients with CKI associated LTC had increased level of sCr (79.1 ± 4.01versus 146.1 ±
6.66 ml/min,P < 0.05) and uCr (1.35 ± 0.08versus 57.66 ± 18.88 ml/min,P < 0.05) compared with
CKI patients without cisplatin-treated tumors. Since patients with renal injury revealed significantly
higher CKI scores and severe proximal tubular cells damage, significant differences were found for
plasma or urine creatinine levels ratios. High expression of uCr/ sCr ratio in the renal is associated
with nephrotoxicity in solid kidney tumors, suggesting uCr may play a role in proximal tubular
injury of LTC, therefore, our data suggest that urinary uCr may be considered to be reliable markers
to monitor renal injury in renal injury patients undergoing LTC.