RGD Reference Report - Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxy-L-proline. - Rat Genome Database

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Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxy-L-proline.

Authors: Khan, SR  Glenton, PA  Byer, KJ 
Citation: Khan SR, etal., Kidney Int. 2006 Sep;70(5):914-23. Epub 2006 Jul 19.
RGD ID: 2289370
Pubmed: (View Article at PubMed) PMID:16850024
DOI: Full-text: DOI:10.1038/sj.ki.5001699

A number of animal models have been developed to investigate calcium oxalate (CaOx) nephrolithiasis. Ethylene glycol (EG)-induced hyperoxaluria in rats is most common, but is criticized because EG and some of its metabolites are nephrotoxic and EG causes metabolic acidosis. Both oxalate (Ox) and CaOx crystals are also injurious to renal epithelial cells. Thus, it is difficult to distinguish the effects of EG and its metabolites from those induced by Ox and CaOx crystals. This study was performed to investigate hydroxy-L-proline (HLP), a common ingredient of many diets, as a hyperoxaluria-inducing agent. In rats, HLP has been shown to induce CaOx nephrolithiasis in only hypercalciuric conditions. Five percent HLP mixed with chow was given to male Sprague-Dawley rats for 63 days, resulting in hyperoxaluria, CaOx crystalluria, and nephrolithiasis. Crystal deposits were surrounded by ED-1-positive inflammatory cells. Cell injury and death was followed by regeneration, as suggested by an increase in proliferating cell nuclear antigen-positive cells. Both osteopontin (OPN) and CD44 were upregulated. Staining for CD44 and OPN was intense in cells lining the tubules that contained crystals. Along with a rise in urinary Ox and lactate dehydrogenase, there were significant increases in 8-isoprostane and hydrogen peroxide excretion, indicating that the oxidative stress induced cell injury. Thus, HLP-induced hyperoxaluria alone can induce CaOx nephrolithiasis in rats.

Annotation

Disease Annotations    
Kidney Calculi  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Cd44  (CD44 molecule (Indian blood group))

Genes (Mus musculus)
Cd44  (CD44 antigen)

Genes (Homo sapiens)
CD44  (CD44 molecule (Indian blood group))


Additional Information