Hereditary X-linked Nephritis

Kidney failure, although generally thought to be a condition associated with old age, can be seen at any age and is not uncommon in dogs under five years old. Juvenile kidney diseases have been reported in many breeds of dogs. However, there are few instances where a genetic basis has been conclusively demonstrated. In cats, juvenile nephropathies are much rarer (as are most inherited problems) because the vast majority of cats are bred from totally unrelated parents. Some renal diseases have been shown to have a familial basis in dogs and cats, and familial renal diseases are well recognized in people.

Hereditary Nephritis

Hereditary nephritis is a group of inherited conditions characterized initially by presence of blood in the urine (hematuria) and slowly progressing to renal insufficiency, a condition in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, maintain electrolyte balance (sodium and potassium), control blood pressure and metabolize calcium. The most severe form of renal insufficiency is kidney failure.

Affected male dogs have excessive amount of protein in the urine, with or without blood. Renal insufficiency usually develops by five months of age and progresses to uremia (excessive amount of toxic nitrogenous and other waste in the blood) and death by eight to ten months. No visual or hearing defects are usually seen in affected male or female dogs.

X-linked hereditary nephritis (HN) in Samoyed dogs is similar to Alport syndrome in humans, a hereditary disease of collagens. The consequence of the defect is progressive renal failure, for which the only available treatments are dialysis and transplantation. Recent studies support the prospect of gene transfer therapy for Alport syndrome.

Bull terrier hereditary nephritis is inherited as an autosomal dominant disease and causes kidney failure at variable ages in affected dogs.

Breeds at Risk

Autosomal dominant Alport syndrome in Dalmatians resembles the disease in Bull terriers but has arisen independently. The mode of inheritance is autosomal dominant. The age at onset of kidney failure is 18 months (range 8 months to 7 years). Affected dogs are not deaf, and do not have the eye abnormalities seen in human X-chromosome-linked or autosomal recessive Alport syndrome. Both males and females may be affected equally often and equally severely.

Angiotensin converting enzyme (ACE) inhibitors have been shown to slow the progression of renal disease in animals and human patients. Treatment improves weight gains and, overall, treated dogs survive 1×36 times longer than affected untreated dogs.

references

1. The Kidney. Peter D. Vize, Adrian S. Woolf, Jonathan B. L. Bard
2. Treatment of X-linked hereditary nephritis in samoyed dogs with angiotensin converting enzyme (ACE) inhibitor. K.M. Grodeckia, M.J. Gainsa, R. Baumal, D.H. Osmond, B. Cotter, V.E.O. Valli and R.M. Jacobsa
3. Genetic cause of X-linked Alport syndrome in a family of domestic dogs. Cox ML, Lees GE, Kashtan CE, Murphy KE.
4. Bull terrier hereditary nephritis: A model for autosomal dominant Alport syndrome. Jennifer C Hood, Judy Savige, Anne Hendtlass, Mary M Kleppel, Clive R Huxtable and Wayne F Robinson
5. A novel model of autosomal dominant Alport syndrome in Dalmatian dogs. Jennifer C. Hood, Clive Huxtable, Ichiro Naito, Carole Smith, Roger Sinclair and Judy Savige
6. Juvenile nephropathies in dogs and cats. Allison Gleadhill, PhD