This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and
aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive
biomarkers of renal dysfunction in
cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single
subcutaneous injection of either saline or
cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days
after treatment. In urine samples we determined
Ala, Glu, Cys and AspAp activities,
proteinuria, N-acetyl-β-D-
glucosaminidase (NAG),
albumin, and
neutrophil gelatinase-associated lipocalin (NGAL). Plasma
creatinine,
creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and
albumin were increased 48 hours
after treatment in the
cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary
aminopeptidase activities and
albuminuria were significantly increased in the
cisplatin 7 mg/kg treated group.
Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma
creatinine,
creatinine clearance and/or kidney
weight/body weight ratio at the end of the experiment and they could be considered as predictive
biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All
aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary
biomarkers of the renal dysfunction induced by
cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.