Skip Navigation LinksHome > March 2013 - Volume 61 - Issue 3 > Urinary Tubular Protein-Based Biomarkers in the Rodent Model...
Journal of Investigative Medicine:
doi: 10.231/JIM.0b013e31828233a8
Original Articles

Urinary Tubular Protein-Based Biomarkers in the Rodent Model of Cisplatin Nephrotoxicity: A Comparative Analysis of Serum Creatinine, Renal Histology, and Urinary KIM-1, NGAL, and NAG in the Initiation, Maintenance, and Recovery Phases of Acute Kidney Injury

Sinha, Vikash MBBS; Vence, Luis M. PhD; Salahudeen, Abdulla K. MD

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Abstract

Background: Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared.

Objective: To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI.

Methods: Sprague-Dawley rats (300–350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed.

Results: A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P < 0.05]. The renal histology scores for brush border loss and tubular necrosis were significantly higher at 12 and 24 hours, respectively, in the CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P < 0.05] and remained elevated through day 10. Both urine NAG and NGAL levels were significantly higher by day 2 in the CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P < 0.05]. Urinary NAG remained elevated for 6 days and NGAL for 3 days.

Conclusions: Our study suggests a temporal hierarchy in the ability of certain urinary protein-based biomarkers to detect AKI after a well-defined tubular injury. Comparative analyses of urinary biomarkers are warranted in clinical settings such as patients receiving CP to discern the time course and pattern of expression.

© 2013 American Federation for Medical Research

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