2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2005121282v1 17/8/2213    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gambaro, G. Articles by Trevisan, A. Search for Related Content PubMed PubMed Citation Articles by Gambaro, G. Articles by Trevisan, A.

Mild Tubular Damage Induces Calcium Oxalate Crystalluria in a Model of Subtle Hyperoxaluria: Evidence that a Second Hit Is Necessary for Renal Lithogenesis

Giovanni Gambaro^*, Maria Luisa Valente, Edoardo Zanetti, Mila Della Barbera, Dorella Del Prete, Angela D’Angelo and Andrea Trevisan

^* Department of Biomedical and Surgical Sciences, Division of Nephrology, University of Verona, Verona, and Institute of Pathology, Department of Environmental Medicine and Public Health, and Department of Medical and Surgical Sciences, Division of Nephrology, University of Padova, Padova, Italy

Address correspondence to: Prof. Giovanni Gambaro, Divisione di Nefrologia, Dipartimento di Scienze Biomediche e Chirurgiche, Università di Verona, Ospedale Maggiore, P.le Stefani 1, 37126 Verona, Italy. Phone: +39-045-8072521; Fax: +39-045-915176; E-mail: giovanni.gambaro{at}univr.it

Received for publication December 12, 2005. Accepted for publication May 9, 2006.

Environment and diet have a major role in calcium nephrolithiasis by affecting urine saturation, but this is not enough to cause lithogenesis; the crystals must adhere to the tubular epithelium (TE), but it is hard to say how environment and nutrition may be involved in this step. The hypothesis that TE damage (known to enhance crystal attachment) is lithogenic in mild hyperoxaluria was tested. Mild hyperoxaluria was induced in male Wistar rats using ethylene glycol (EG; 0.5% in water) for 21 d, and TE damage was induced by intraperitoneal administration of hexachloro-1:3-butadiene (HCBD; an industrial nephrotoxin) at 10, 25, and 50 mg/kg body wt on days 7 and 14. These EG and HCBD concentrations were chosen to span from suboptimal to very low doses as far as effects on crystalluria and TE damage are concerned. Enzymuria, proteinuria, oxaluria, crystalluria, and renal pathology were investigated. All HCBD dosages induced crystalluria in mildly hyperoxaluric rats, but no intrarenal crystals were found. EG alone induced very mild hyperoxaluria but no damage to the renal tubule observable on transmission electron microscopy, and it did not cause crystalluria or intrarenal crystals. HCBD with the concomitant administration of EG caused apoptosis of the TE at the two highest dosages after the second injection. Apoptosis did not correlate with crystalluria. A TE toxin is needed for crystallogenesis to occur in borderline metabolic conditions. It may take more than just a metabolic predisposition for calcium nephrolithiasis to occur, and the second hit could come from an environmental pollutant such as HCBD.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673