Submitted on December 29, 2007
Accepted on March 9, 2008
Calcium Oxalate crystal deposition in the kidneys of hypercalciuric mice with disrupted type IIa sodium/phosphate (Npt2a) co-transporter
Saeed R. Khan1* and Patricia A Glenton2
1 Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida, United States
2 Pathology, Immunology and laboratory Medicine, University of Florida College of medicine, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: khan{at}pathology.ufl.edu.
The most common theories about the pathogenesis of kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of CaOx in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate co-transporter. Npt2a KO mice are hypercalciuric and produce CaP deposits in their renal tubules. Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO mice as well as the normocalciuric control B6 mice. Only the KO mice produced CaOx crystal deposits in their kidneys. But the CaOx crystals deposited separately from the CaP deposits. Perhaps CaP deposits were not available for a CaOx overgrowth. These results also validate earlier animal model observations which showed that CaP substrate is not required for renal deposition of CaOx and that other factors such as local supersaturation, may be involved. Absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis.
