Hereditary Nephritis (Hereditary Samoyed Glomerulopathy or X-Linked Nephritis)

Nephritis literally means inflammation of the nephron, the basic unit of the kidney. Hereditary nephritis means the condition is inherited rather than caused by environmental factors. It is characterized by progressive kidney dysfunction ultimately leading to kidney failure and death.

In Samoyeds, hereditary nephritis is X-linked. It is transmitted by mothers to sons through the X chromosome. The disease is more severe in males because they have only one X chromosome, with death typically occurring by 15 months. Since females have two X chromosomes (and only one is typically affected) their disease is less serious.

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Link includes diagrams of the kidney/glomerulus

Canine x-linked nephritis, or Hereditary Samoyed Glomerulopathy, was first described in a family of Canadian Samoyeds in 1977. The specific mutation has been identified - a change in one DNA base pair in the COL4A5 gene results in a 90% reduction in the amount of type IV collagen made in the kidney. Without enough of this protein, the glomerular basement membrane in the glomerulus of the kidney is abnormal. This is the same gene that is abnormal in Alport’s syndrome, a form of human hereditary nephritis. Because of this, Canine Hereditary X-linked Nephritis has been used as a model to study potential treatments for Alport’s syndrome.

Signs and Symptoms

These symptoms start very early in affected male puppies:

Excessive drinking and urination
Vomiting, poor appetite and weight loss
Lethargy, muscle weakness
Proteinuria (protein in the urine). If severe protein loss is present there can be edema (swelling) of abdomen and paws.
Hematuria (blood in the urine)
Anemia from chronic renal failure
Decrease in kidney function (decreased glomerular filtration rate)
Progression to renal failure, with males dying by 15 months of age.

Carrier females also lose weight and develop proteinuria, but the disease progresses much slower and renal failure occurs later in life.

Causes

The cause in Samoyeds is an X-linked inherited genetic defect. The disease is carried on the X-chromosome. Males have only one X chromosome (coming from their mother) and hence the disease is more serious. Because females have two X chromosomes (one from their mother, one from their father) the disease is not so serious.

Risk Factors

History of hereditary nephritis in a family.

Diagnostic Tests

Urinalysis to check for protein and blood
CBC and serum biochemistry tests
Urine protein/creatinine ratio to determine severity of protein loss in urine (24 hour collection of urine is required to perform this test)
Blood pressure measurements

There is a DNA (genetic) test for this inherited disease that may be obtained from Embark or other laboratories.

Treatment Guidelines

Note: Treatment of animals should only be performed by a licensed veterinarian. Veterinarians should consult the current literature and current pharmacological formularies before initiating any treatment protocol.

There is no curative treatment for hereditary nephritis. Special diets (low protein, low salt, low phosphorous) may be prescribed as palliative measures. Medications may be used to control blood pressure. Treatment with ACE inhibitors, a type of blood pressure medication, may improve the life span a few months, but is not curative. There is also some research evidence that dietary modification can slow the process.

Management

This is a genetically transmitted disorder. Males with this defect should not be bred. Females from a line with this disorder should not be bred unless their DNA has been tested and found to be clear of the mutation that causes the disorder. Affected bitches and carriers should not be bred.

DNA test from Embark

References

Glomerular Disease in: The Merck Veterinary Manual four bonesrating

Bernard et al. 1977. Familial Renal Disease in Samoyed Dogs. Can Vet Journal 18: 181-189. three bonesrating

Zheng et al. 1994. Canine X chromosome-linked hereditary nephritis: A genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha5 chain of collagen type IV . PNAS 91: 3989-3993. three bonesrating

Glomerulopathies. Page 376 in: Veterinary pediatrics: dogs and cats from birth to six months by JD Hoskins. Saunders 2001. four bonesrating

Canine and Murine Hereditary Nephritis. Page 542 in: Diseases of the kidney and urinary tract by RW Schrier. Lippincott Williams & Wilkins, 2007. four bonesrating