Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: Dalmatian dog model.
OBJECTIVE
To study the role of urinary inhibitors on crystallization-nephrocalcin, Tamm-Horsfall protein (THP), and glycosaminoglycans (GAGs)-in hyperuricosuric nephrolithiasis using Dalmatian dogs, a breed well-known for high levels of uric acid excretion, in an in vivo model.


METHODS
Urine samples were collected from 10 stone-forming Dalmatian dogs and from 5 age-matched Dalmatians without kidney stones. Purine derivatives present in urine were studied by high-performance liquid chromatography. THP, GAGs, and nephrocalcin were isolated and measured.


RESULTS
As expected, the Dalmatians excreted a large amount of uric acid in urine, but without differences between the two groups (0.42 +/- 0.08 mg/mg creatinine versus 0.48 +/- 0.11 mg/mg creatinine for stone-forming and healthy Dalmatians, respectively, P = 0.64). No other metabolites were derived from purine in their urine. Stone-forming Dalmatians showed significantly lower urinary excretion of THP than did normal Dalmatians (0.09 +/- 0.03 mg/mg creatinine versus 0.21 +/- 0.03 mg/mg creatinine, P <0.03). The urinary excretion of GAGs was lower in the stone-forming Dalmatians, although the difference was not statistically significant. Inhibition of calcium oxalate monohydrate crystal growth caused by nephrocalcin isoforms from healthy and stone-forming dogs were in the same order of approximately 10(-7) M, as calculated from a Langmuir isotherm type plot.


CONCLUSIONS
The urinary excretion of THP and GAGs was decreased in stone-forming Dalmatians compared with healthy ones. Our results support the suitability of Dalmatian dogs as an in vivo model to investigate the interrelationship of urine inhibitors of crystallization and hyperuricosuria.
Carvalho
Mauricio
M
Kidney Stone Program, Division of Biological Sciences, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.
Lulich
Jody P
JP
Osborne
Carl A
CA
Nakagawa
Yasushi
Y
D000818:Animals; D003460:Crystallization; D004285:Dogs; D005260:Female; D006023:Glycoproteins / Q000652:urine*; D007669:Kidney Calculi / Q000652:urine*; D008297:Male; D009088:Mucoproteins / Q000652:urine*; D014527:Uric Acid / Q000737:chemistry*; D014556:Urine / Q000737:chemistry; D058949:Uromodulin
D006023:Glycoproteins; D009088:Mucoproteins; D058949:Uromodulin; C029490:nephrocalcin; D014527:Uric Acid