Cystinuria in Newfoundland Dogs
By Sharon Gwaltney DVM PhD

Cystinuria is an inherited disorder caused by a defect in the transport of cystine, an amino acid, in the kidney tubules. Normally, cystine that is filtered in the kidney is reabsorbed within the tubules, resulting in little cystine in the urine. Dogs with cystinuria do not properly reabsorb cystine (and a few other amino acids) in the kidney tubules, causing the urine to contain abnormally high levels of cystine. Cystine is insoluble in neutral pH or acidic urine, so excess urinary cystine results in formation of cystine crystals, which in turn can lead to formation of cystine calculi (stones) in the kidney and/or bladder. Because males have long, narrow urethras compared to females, irritation and blockage by calculi is much more common in the male. Males with cystinuria suffer repeated inflammations of the urinary tract and are at risk for urinary blockage, which can, if not treated promptly, lead to kidney failure, bladder rupture, and death.

Cystinuria has been reported in many breeds (and mixed breeds) of dogs. Although Newfoundlands are not the breed most commonly associated with cystinuria, Newfoundlands are at an increased risk of developing cystine calculi formation compared to most other breeds; cystinuria in Newfoundlands is inherited as an autosomal recessive trait. The average age of onset of clinical signs attributable to cystinuria in other dog breeds is about 4.8 years, but in Newfoundlands, signs appear as early as 6 months to 1 year, suggesting that Newfoundlands suffer from a more severe form of the disorder than do other breeds. Recurrence of calculi following surgical removal also occurs much more rapidly in Newfoundlands than in other breeds.

Cystinuria in humans and dogs is generally treated with compounds that bind cystine and prevent crystal formation. The two most common drugs of choice are 2-mercaptopropionylglycine (MPG)and D-penicillamine. Little information is available on effective dosages in Newfoundlands, however at least one study indicated that cystinuric Newfoundlands require higher dosages of MPG than other dogs with cystinuria; in the same study, D-penicillamine was found to be of minimal benefit in reducing cystine calculi. This may relate to the fact that Newfoundlands suffer from a more severe form of the disorder than other breeds. Treatment with MPG can, in some cases, result in dissolution of cystine calculi, eliminating the need for surgical removal of the stones. Unfortunately, some Newfoundlands are poorly responsive to medical treatment, suffering recurring bouts of urinary dysfunction and oftentimes requiring surgery to resolve urinary calculi.

Cystinuria should be suspected in young male Newfoundlands with evidence of chronic urinary problems (difficult urination, blood in urine, inability to urinate). Cystinuric bitches are often asymptomatic, and it is important that "puppy vaginitis/cystitis" (both not uncommon conditions in pre-pubertal bitches) not be mistaken for cystinuria. Pups from suspect or known carrier parents should be evaluated at an early age, as early therapeutic intervention may help reduce the formation of urinary calculi.

Cystinuria is diagnosed through the identification of characteristic crystals in the urine. Cystine can be identified in the urine as early as 2 days of age using a nitroprusside spot test or paper chromatography; either of these tests can be used to further confirm a suspected case of cystinuria. This means of testing for cystinuria requires the submission of urine, either in a vial or spotted onto filter paper. While the nitroprusside spot test will detect affected dogs, it will not determine whether an individual carries a gene for cystinuria and could therefore, if bred to another carrier or an affected dog, produce affected offspring. Until recently, the nitroprusside spot test was the only available means of testing for cystinuria.

Fortunately, thanks to the work of veterinary researcher Dr. Paula Henthorn at the University of Pennsylvania School of Veterinary Medicine, there is now a DNA test available which can determine the genetic status of individual Newfoundlands. This DNA test, requiring only a small blood sample, will be invaluable in helping Newfoundland breeders make educated decisions on breeding dogs, and it will hopefully reduce the number of Newfoundlands produced with this severe, potentially life-threatening condition.

Both the nitroprusside spot test and the DNA test are available through the Josephine Deubler Genetic Disease Testing Laboratory at the University of Pennsylvania. Further information on cystinuria and the available tests, as well as sample submission forms can be obtained on the World Wide Web at: www.vet.upenn.edu/penngen/testing.html or by mail from Dr. Urs Giger/Room 4006, 3850 Spruce Street VHUP, Philadelphia, PA, 19104-6010. As of September 1999, the cost of the nitroprusside test was $18 per sample, and the cost of the DNA test was $75.

REFERENCES: Case, LC, et.al. Cystine-containing urinary calculi in dogs: 102 cases. Journal of the American Veterinary Medical Association 1992 201(1):129 Casal, ML., et.al. Inheritance of cystinuria and renal defect in Newfoundlands. Journal of the American Veterinary Medical Association 1995 207(12):1585.


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Sharon Gwaltney DVM, PhD
gwalt@napcc.aspca.org