RT Journal Article
T1 Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats
A1 Quesada, Andrés
A1 Vargas, Félix
A1 Montoro-Molina, Sebastián
A1 O'Valle, Francisco
A1 Rodríguez-Martínez, María Dolores
A1 Osuna, Antonio
A1 Prieto, Isabel
A1 Ramírez, Manuel
A1 Wangensteen, Rosemary
K1 Aminopeptidasas
K1 Cisplatino
K1 Ratas Wistar
K1 Marcadores Biológicos
K1 Insuficiencia Renal
AB 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.
PB Public Library of Science
YR 2012
FD 2012-07-05
LK http://hdl.handle.net/10668/562
UL http://hdl.handle.net/10668/562
LA en
NO Quesada A, Vargas F, Montoro-Molina S, O'Valle F, Rodríguez-Martínez MD, Osuna A, et al. Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. PLoS ONE; 7(7):e40402
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 11, 2025