Inheritance of cystinuria and renal defect in Newfoundlands.
OBJECTIVE
To describe clinical features, characterize metabolic renal abnormalities, and evaluate mode of inheritance of cystinuria in Newfoundlands.


METHODS
Prospective study.


METHODS
Two families of Newfoundlands including 11 dogs with dysuria, stranguria, or obstruction attributable to cystine calculi.


METHODS
Urinalysis and nitroprusside spot tests were performed to evaluate cystinuria in the affected dogs. All calculi were analyzed by crystallography. Amino acid concentrations in urine and plasma of affected dogs were compared with those in clinically normal related dogs. Renal fractional excretion and reabsorption of amino acids were determined in 5 affected Newfoundlands.


RESULTS
Nine dogs had pure cystine calculi in the bladder, and 4 of these had renal cystine calculi. Affected dogs persistently excreted excessive amounts of cystine (> 500 nmol/mg of creatinine; reference = 54 +/- 38 nmol/mg of creatinine) and had typical cystine crystals in acidic urine. Urinary excretion of ornithine, lysine, and arginine was also high. Dogs with cystinuria had complete lack of reabsorption and active secretion of cystine, and reabsorption of lysine, ornithine, and arginine was moderately impaired. Although clinical signs of urinary obstruction were observed only in males, cystinuric male and female offspring were produced from noncystinuric parents, consistent with an autosomal recessive mode of inheritance. Obligate heterozygotes did not have clinical signs, and had normal urinary cystine content and renal amino acid reabsorption.


CONCLUSIONS
Because detection of carriers by routine urinalysis is currently not possible, Newfoundlands with cystinuria and their parents and offspring should be excluded from breeding.
D000818:Animals; D001947:Breeding; D003555:Cystinuria / Q000150:complications / Q000235:genetics / Q000662:veterinary*; D004283:Dog Diseases / Q000235:genetics* / Q000601:surgery; D004285:Dogs; D005260:Female; D008297:Male; D010375:Pedigree; D011446:Prospective Studies; D012008:Recurrence; D014545:Urinary Calculi / Q000209:etiology / Q000628:therapy / Q000662:veterinary