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Título : Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats
Autor : Quesada, Andrés
Vargas, Félix
Montoro-Molina, Sebastián
O'Valle, Francisco
Rodríguez-Martínez, María Dolores
Osuna, Antonio
Prieto, Isabel
Ramírez, Manuel
Wangensteen, Rosemary
Filiación: [Quesada,A; Montoro-Molina,S; Prieto,I;Ramírez,M; Wangensteen,R] Área de Fisiología, Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain. [Vargas,F] Departamento de Fisiología, Facultad de Medicina, Universidad de Granada, Granada, Spain. [O'Valle,F; Rodríguez-Martínez,MD] Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de Granada, IBIMER Granada, Spain. [Osuna,A] Servicio de Nefrología, Hospital Virgen de las Nieves, Granada, Spain.
Palabras clave : Aminopeptidasas
Ratas Wistar
Marcadores Biológicos
Insuficiencia Renal
MeSH: Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Exopeptidases::Aminopeptidases
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Chlorine Compounds::Cisplatin
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers
Medical Subject Headings::Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency
Fecha de publicación : 5-Jul-2012
Editorial : Public Library of Science
Cita Bibliográfica: 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
Abstract: 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.
Descripción : Journal Article; Research Support, Non-U.S. Gov't;
Versión del editor :
DOI: 10.1371/journal.pone.0040402
ISSN : 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de las Nieves

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