Role of urinary inhibitors of crystallization in uric acid nephrolithiasis: Dalmatian dog model

Objectives. 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 ∼ 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.