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Table of Contents
Vol. 24, No. 3, 2004
Issue release date: May – June
Section title: Original Report: Laboratory Investigation
Am J Nephrol 2004;24:307–315
(DOI:10.1159/000078452)

Neutrophil Gelatinase-Associated Lipocalin: A Novel Early Urinary Biomarker for Cisplatin Nephrotoxicity

Mishra J.a · Mori K.b · Ma Q.a · Kelly C.a · Barasch J.b · Devarajan P.a
aNephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, and bNephrology, College of Physicians and Surgeons, Columbia University, NewYork,N.Y., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: February 17, 2004
Accepted: March 26, 2004
Published online: July 06, 2004
Issue release date: May – June

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN

Abstract

Background: Cisplatin is one of the most widely used chemotherapeutic agents, but the risk of nephrotoxicity frequently hinders the use of higher doses to maximize its antineoplastic effects. The lack of early biomarkers has impaired our ability to initiate potential therapeutic or preventive interventions in cisplatin nephrotoxicity in a timely manner. In this study, we have explored the expression and urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in a mouse model of cisplatin-induced nephrotoxic injury. Methods: Mice were subjected to intraperitoneal injections of 20 mg/kg (high dose) or 5 mg/kg (low dose) cisplatin. The expression of NGAL was measured in the kidney and urine by Western analysis and immunofluorescence, and compared to changes in serum creatinine and urinary N-acetyl-β-D-glucosaminidase (NAG). Results: Cisplatin resulted in tubule cell necrosis and apoptosis following the high dose, but not the low dose. By Western analysis, NGAL protein was rapidly induced in the kidney within 3 h of high-dose cisplatin. By immunofluorescence, NGAL was induced predominantly in proximal tubule cells in a punctate cytoplasmic distribution, reminiscent of a secreted protein. NGAL was easily detected in the urine by Western analysis within 3 h of cisplatin administration in a dose- and duration-dependent manner. By comparison, changes in urinary NAG or serum creatinine were not evident until 96 h after cisplatin. Using defined concentrations of purified recombinant NGAL, urinary NGAL excretion following cisplatin administration was quantified to be in the 20–80 ng/ml range. Conclusion: The results indicate that NGAL represents an early and quantitative urinary biomarker for cisplatin nephrotoxicity.

© 2004 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Report: Laboratory Investigation

Received: February 17, 2004
Accepted: March 26, 2004
Published online: July 06, 2004
Issue release date: May – June

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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