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Chronic renal diseases in the dog are not uncommon

Renal dysplasia and Familial Nephropathy – Two Important and Serious Diseases in the Bernese Mountain Dog Breed. Chronic renal diseases in the dog are not uncommon Two of these are most likely of genetic origin: renal dysplasia and familial nephropathy

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Chronic renal diseases in the dog are not uncommon

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  1. Renal dysplasia and Familial Nephropathy – Two Important and Serious Diseases in the Bernese Mountain Dog Breed

  2. Chronic renal diseases in the dog are not uncommon • Two of these are most likely of genetic origin: renal dysplasia and familial nephropathy • Of the mortality cases of kidney diseases registered at the insurance company Agria about half are caused by renal dysplasia (RD) and familial nephropathy (FN) together

  3. The primary lesions or abnormalities are found in the glomeruli • The functional unit of the kidney is the nephron

  4. RD and FN • Clinical signs often observed include excessive water consumption (polydipsia), excessive urine volume (polyuria), vomiting, depression, inappetence and weight loss • Blood chemistry reveals non-regenerative anemia, high serum urea nitrogen, low hemoglobulin values and normal white cell count. Urine analysis shows proteinuria in most cases and a low specific gravity

  5. RD and FN • The prognosis for the diseases are poor. • Most of the dogs die or have to be euthanased shortly after admission to the clinic

  6. Diagnosis of RD and FN

  7. Diagnosis of RD • For an accurate diagnosis a comprehensive pathological examination must be performed • For RD a wedge renal biopsy of the renal cortex is the most accurate method since it provides a large number of glomeruli for examination

  8. Diagnosis of RD • RD is characterised by unnormal development (dysplasia) of the renal tissue, such as immature glomeruli, immature connective tissue, and tubular dysplasia

  9. Diagnosis of FN • The morphological glomerular lesions are those of a membrano-proliferative glomerulinephritis with concomitant interstitial nephritis • A diagnosis is much helped by electron microscopy or immunostaining

  10. Cases of RD in Sweden

  11. Cases of RD in Sweden • The mean age is 1 year and 4.5 months • Almost 63% of the cases were bitches • The prevalences of cases were ranging from 0.18% to 0.73% for each year with cases with an average prevalence of 0.21% • Cases are more prevalent in certain breed lines • The inbreeding coefficient was high for the first cases but on a low level the last 12 years • The health programme introduced 1998 has not been shown so far to have reduced the number of cases • Underreporting of cases must be accounted for

  12. A special case of RD • Zandrina’s Hubert was diagnosed with RD at the age of 7 years and 2 months • RD is the young dog’s disease and it is very uncommon for such an old dog to be diagnosed with RD • The diagnosis was confirmed by American and Swedish pathologists

  13. A special case of RD • Zandrina’s Hubert was exported to USA from Sweden • Before the export he had two litters of 9 puppies and by now 30 grandchildren and 28 grandgrandchildren in Sweden • So far no cases of RD in his offsprings • In USA he had 10 litters of 34 puppies and ? grandchildren • This is the first time a dog with RD has been used in breeding in Sweden

  14. Cases of FN in Sweden

  15. Cases of FN in Sweden • The mean age is 3 years and 7.5 months • 78% of the cases were bitches • The prevalences of cases were ranging from 0.16% to 0.73% for each year with cases with an average prevalence of 0.20%; a higher incidence the last 4 years • Cases are more prevalent in certain breed lines • The inbreeding coefficient was low for all the cases except one with 4.3% • A health programme is not introduced yet • Underreporting of cases must be accounted for • Two stud dogs, S42355/99 Macis Zam Mont Morzy and VDHSSVBS36372 Hagen Vom Limespfad, are carriers of both RD and FN disease genes

  16. What is causing RD? • Surprisingly little is known about RD in the Bernese Mountain Dog • One report from Canada describes a probable case of RD in 1999, however no autopsy was performed • RD has been described in over 80 breeds • RD has been proposed to be caused by an autosomal recessive gene in Shih Tzu dogs • Another report suggests an autosomal dominance pattern with incomplete penetrance in the Shih Tzu • A Canadian company is offering a RD DNA test for Bernese Mountain Dogs

  17. Research on RD in Sweden

  18. What is causing FN? • Several reports describe FN in the Bernese Mountain Dog, the first one in 1994 • The dogs diagnosed with FN had also high antibody titres to Borrelia Burgdorferi (Lyme disease), which gave the notion that Borrelia was causing the disease in dogs predisposed by carrying an autosomal recessive disease gene • However, studies presented in 2007 showed that Bernese Mountain Dogs were more susceptible to infection with Borrelia species than other breeds and not connected to FN

  19. What is causing FN? • The pattern of inheritance is not known for the Bernese Mountain Dog • Three genes for FN in the English Cocker Spaniel breed are characterised and a DNA test is available • A mutation in one of these genes, COL4A5, the disease has an X-linked mode of inheritance • A mutation in one of the other two genes, COL4A3 or COL4A4, the disease has an autosomal recessive mode of inheritance

  20. Future research • A reliable DNA test will be developed very soon for RD • If analogous mutated genes to the ones in the English Cocker Spaniel responsible for FN are found in the Bernese Mountain Dog, a DNA test is easily developed

  21. Diagnostic test requirements • For reliable and true test results it is of utter importance that the laboratories performing the tests have a quality assurance (QA) system installed and the tests are validated • An accreditated laboratory safeguards every step in the test procedure • If somethings goes wrong, i.e. a faulty test result, it is always possible to trace back where in the process it happened • Of 13 laboratories found on the net offering and performing DNA tests in dogs only two were accredited

  22. Diagnostic test requirements • A test must be validated so it is highly likely that it gives true negative and positive results • The validation is performed on many samples, maybe 100, from one group of dogs defined as carrying the mutated gene and one group of dogs defined as not carrying the mutated gene • The intrinsic property of a diagnostic test is that negative results almost always are true negatives but positive test can be false positives, especially if the mutated gene is rarely present in the population (a low prevalence) • If so, most of the positive results are false • Additional complementary or confirmatory tests must then be available

  23. This is the End • Jump for Joy

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