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

Mauricio Carvalho, Jody P. Lulich, Carl A. Osborne, Yasushi Nakagawa

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)566-570
Number of pages5
Issue number3
StatePublished - Sep 1 2003


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