Defective urinary crystallization inhibition and urinary stone formation.
BACKGROUND
Nephrocalcin (NC) is a glycoprotein produced in the kidney and inhibits calcium oxalate crystal formation. It has been separated into 4 isoforms (A, B, C, and D) and found that (A + B) are more abundant than (C + D) in urine of healthy subjects, but the reverse is seen in human urine of kidney stone patients. To further examine the role of this protein in inhibition of urinary crystallization, nephrocalcin isoforms were purified from 2 genetically pure dog species.


METHODS
We studied healthy Beagles, known to be non-stone forming dogs, and Mini-Schnauzers, known to be calcium oxalate stone formers. NC was isolated and purified from each group. Urinary biochemistry and calcium oxalate crystal growth inhibition were measured.


RESULTS
Specific crystal growth inhibition activity was significantly higher in non-stone forming dogs (9.79 +/- 2.25 in Beagles vs. 2.75 +/- 1.34 of Mini-Schnauzers, p < 0.005). Dissociation constants toward calcium oxalate monohydrate were 10-fold different, with Beagles' isoforms being 10 times stronger inhibitors compare to those of Mini-Schnauzers'. Isoforms C + D of NC were the main isoforms isolated in stone-forming dogs.


CONCLUSIONS
NC of these two species of dogs differently affects calcium oxalate crystallization and might have a role in determining ulterior urinary stone formation.
Carvalho
Mauricio
M
Kidney Stone Program, Department of Internal Medicine, Federal University of Parana, Curitiba, Parana, Brazil.
Lulich
Jody P
JP
Osborne
Carl A
CA
Nakagawa
Yasushi
Y
D000818:Animals; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors* / Q000652:urine; D003460:Crystallization; D004285:Dogs; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology* / Q000652:urine; D008297:Male; D013053:Spectrophotometry; D014545:Urinary Calculi / Q000517:prevention & control; D014556:Urine / Q000737:chemistry
D006023:Glycoproteins; C029490:nephrocalcin; D002129:Calcium Oxalate