Mild Tubular Damage Induces Calcium Oxalate Crystalluria in a Model of Subtle Hyperoxaluria
Open Access
- 1 August 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 17 (8), 2213-2219
- https://doi.org/10.1681/asn.2005121282
Abstract
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.Keywords
This publication has 27 references indexed in Scilit:
- OXALATE TOXICITY IN CULTURED MOUSE INNER MEDULLARY COLLECTING DUCT CELLSJournal of Urology, 2005
- Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditionsInternational Journal of Urology, 2005
- FREE RADICAL SCAVENGERS, CATALASE AND SUPEROXIDE DISMUTASE PROVIDE PROTECTION FROM OXALATE-ASSOCIATED INJURY TO LLC-PK 1 AND MDCK CELLSJournal of Urology, 2000
- Animal models of kidney stone formation: an analysisWorld Journal of Urology, 1997
- Calcium oxalate nephrolithiasis, a free or fixed particle diseaseKidney International, 1994
- A mechanism of haloalkene-induced renal carcinogenesis.Environmental Health Perspectives, 1990
- Dietary factors in the pathogenesis and prophylaxis of calcium nephrolithiasisKidney International, 1988
- Necrosis of the pars recta (S3 segment) of the rat kidney produced by hexachloro 1:3 butadieneThe Journal of Pathology, 1982
- Should Recurrent Calcium Oxalate Stone formers become Vegetarians?BJU International, 1979
- Hexachlorobutadiene residues in aquatic fauna from surface water fed by the river rhineScience of The Total Environment, 1976