Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

Cocker Spaniel

Cocker Spaniel (English and American)

Familial Nephropathy

Related terms: glomerulopathy; hereditary nephritis; kidney disease; Alport-like syndrome, autosomal nephritis; progressive hereditary nephritis.

VeNom term:  Familial Nephropathy (VeNom code: 738).

Related conditions: kidney disease; azotemia; hyperphosphatemia.

Outline: Familial nephropathy describes an inherited disease that occurs in the Cocker spaniel breed and in which young dogs suffer from early-onset kidney failure. Affected dogs are born with an abnormal structure in the walls of their kidney tubules, meaning they are unable to remove waste products from the blood and to produce urine as they normally would do. This in turn causes further damage to the kidneys. The condition has a rapid onset and affects young dogs, usually between 6 months and 2 years of age and is ultimately fatal to dogs.

The clinical signs of familial nephropathy include excessive thirst and urination, loss of appetite, lethargy, vomiting, anorexia, halitosis (bad breath), poor coat quality and pale mucous membranes. A diagnosis can be made based on the presence of blood proteins in the urine and/or abnormally high levels of waste products in the blood. 

The disease is a recessive trait but the exact mutation has not been identified. Careful breeding programmes have helped to reduce the number of dogs affected. 


Summary of Information

(for more information click on the links below)

1. Brief description

Familial nephropathy describes a disease of the kidneys that is inherited in Cocker spaniels and is one in which young dogs suffer from early-onset kidney failure. Dogs with the condition are born with an abnormal structure in the walls of the kidney tubules, which affects the dog’s ability to remove waste products from the blood and to produce urine. The walls of the kidney tubules are excessively leaky resulting in abnormally high levels of protein passing from the blood into the urine, and this leads to further damage to the kidney tubule walls. Familial nephropathy is progressive and ultimately fatal, since the damage to the kidneys is irreparable and eventually the kidneys cease to function. The condition has a rapid onset and affects young dogs, usually between 6 months and 2 years of age.

The clinical signs of familial nephropathy are usually the same as those observed generally for chronic kidney failure of any cause, and include excessive thirst and urination, loss of appetite, lethargy, vomiting, anorexia, halitosis (bad breath), poor coat quality and pale mucous membranes. These signs are non-specific and so an early diagnosis can be difficult to make.

2. Intensity of welfare impact    

Familial nephropathy affects young dogs and the disease is progressive, and ultimately fatal for dogs. Affected dogs experience loss of appetite, vomiting, nausea and abdominal pain as a result of the kidneys lack of ability to excrete waste products.

There is no cure for familial nephropathy, but diets formulated for dogs with renal failure, or administration of an angiotensin converting enzyme inhibitor can reduce the clinical signs.

3. Duration of welfare impact

Most dogs with familial nephropathy have abnormally high levels of proteins in the urine (proteinuria) before one year of age, and will develop kidney failure between 6 months and 2 years of age. However, the rate of disease progression varies between individuals, and some dogs can become seriously ill at a more rapid rate than others.

4. Number of animals affected

To date, there are no published data available for the number of dogs affected by this condition. Familial nephropathy has been reported to affect 11% of English Cocker spaniels in Europe (http://www.antagene.com/en/no/familial-nephropathy-english-cocker-spaniel-breed) but this statistic should be used cautiously since no supporting evidence is provided.

5. Diagnosis

The clinical signs of familial nephropathy are difficult to distinguish from those associated with kidney damage caused by other diseases, and an early diagnosis may be difficult to make. In young dogs, persistently high levels of protein in the urine is most often due to familial nephropathy and therefore the best diagnostic tool to start with is urine sampling. A biopsy will be needed to confirm diagnosis.

6. Genetics

Familial nephropathy is a simple inherited trait which is autosomal (ie not carried on the sex chromosomes thus affects both males and females) and recessive. This means a dog needs to inherit two copies of the mutated gene for it to be affected by the disease. If a dog only has one copy of the mutation, the dog will not be affected but is a carrier, and may pass on the mutated gene to some of their offspring if the other parent is affected or a carrier also.

7. How do you know if an animal is a carrier or likely to become affected?

DNA testing, available in North America and Europe, can be used to identify the mutation for familial nephropathy in Cocker spaniels, with good reliability. DNA can be analysed from either blood samples or mouth swabs. The test can identify dogs that are affected, carriers and those clear of the condition.

8. Methods and prospects for elimination of the problem

Efforts are ongoing to eliminate the disease from the Cocker spaniel breed using DNA testing and careful breeding practices. It is advised to mate only two clear dogs, or one clear and one carrier dog, to produce unaffected offspring. Mating affected dogs, or two carriers will produce some offspring that are affected by the condition, and so this is not advised.


For further details about this condition, please click on the following:
(these link to items down this page)


1. Clinical and pathological effects

Familial nephropathy describes a disease in which young dogs suffer from early-onset kidney failure. It affects dogs within the same family (familial) and is an inherited disease in the Cocker Spaniel breed.

The main function of the kidneys is to regulate the chemical composition of the blood through the filtering of excessive fluid and waste products from it and the production of urine. Kidneys are made up of hundreds of thousands of small structures called nephrons, each of which comprises of a glomerulus and a tubule and contributes to filtering of the blood of toxins and waste products. Blood flowing through the kidney passes through the glomerulus - which is a network of fine capillaries - and in the process fluid and chemicals are filtered out of the blood into the tubules. As this passes down the tubule much of this water is reabsorbed back into the blood, as are some of the chemicals, but any excess and the waste products are eventually excreted as urine.

In familial nephropathy, a genetic mutation causes molecular abnormalities of collagen (a protein) that makes up the connective tissue which forms the walls of the glomerular capillaries (Lees et al 1997; Nowend et al 2012). Healthy glomerular capillary walls consist of several layers of cells – an inner and outer layer of cells, and a middle layer of extracellular matrix material called the glomerular basement membrane (GBM). The GBM contains a network of type IV collagen molecules that are crucial to the maintenance of the normal structure and function of glomerular capillary walls. The type IV collagen network in the GBM is made up of 3 distinct chains of proteins, and each of these peptide chains is encoded by a separate gene. In Cocker spaniels with familial nephropathy, two of the three peptide chains (COL4A3 and COL4A4) are completely absent and this results in abnormalities in the structure of the collagen network of the GBM. This abnormality in structure is very distinctive of familial nephropathy in Cocker spaniels and is found in affected dogs from birth onwards. Despite this abnormality, the kidneys of affected dogs initially develop normally and function properly. However, over time the structure of the GBM starts to change and become progressively thickened, lesioned and split. Because of this, the kidneys of affected dogs cannot filter blood properly, and blood proteins, such as albumin and globulins, begin to leak into the urine. This leads to damage to the tubules and once the nephron is severely damaged or destroyed it cannot be replaced.

Affected dogs also have a deficiency of proteins involved in the normal functioning of the immune system, the IgG and IgA immunoglobulins, which may make them more prone to infections and allergies. Since the kidneys are ineffectively filtering blood, affected dogs also have abnormally high levels of nitrogen-containing compounds in the blood (termed azotaemia), such as urea, creatinine and other body waste compounds, and abnormally high levels of phosphate (hyperphosphataemia). Metabolic acidosis, in which the acidity of the blood increases, may also occur since the kidneys are not effectively regulating the pH of the blood, which can cause nausea, vomiting, and abdominal pain and can be fatal if left unchecked. In severe renal failure, isosthenuria will occur, where the molecular concentration of the urine differs little from that blood plasma, since the kidneys have a reduced ability to concentrate or dilute the urine produced.

The condition has a rapid onset and affects young dogs, usually between 6 months and 2 years of age. The clinical signs of familial nephropathy are usually the same as those observed generally for chronic kidney failure of any cause, and include excessive thirst and urination, loss of appetite, lethargy, vomiting, anorexia, halitosis (bad breath), poor coat quality and pale mucous membranes (Chew et al 2011). These signs are non-specific and so an early diagnosis is difficult to make. The condition has been recognised in Cocker spaniels worldwide.

Familial nephropathy is progressive and ultimately fatal. The rate of disease progression in affected dogs is more rapid in some individuals than others. Treatments may slow the rate of renal disease progression, but only by several weeks or months at most. The rate of progression is usually rapid in the late stages of the condition; once an affected dog has developed moderate build-up of waste products in the blood (azotaemia and hyperphosphataemia). In such cases, the condition usually progresses to the terminal stage within 3 to 6 weeks.

Return to top

2. Intensity of welfare impact

Familial nephropathy affects young dogs and the welfare impact is progressive, severe and ultimately fatal for dogs. It causes slow or stunted growth rate as the puppies develop and as the kidney damage develops, dogs will start to feel unwell. Affected dogs will experience loss of appetite, vomiting, nausea and potentially abdominal pain as a result of the kidneys lack of ability to excrete waste products. As the disease progressives to later stages, these problems will become more severe and dogs will have a reduced appetite and become very weak, leading to terminal renal failure.

There is no cure for familial nephropathy, but treatments can be given to slow the rate of kidney damage and to reduce the effect of the symptoms. Specialised diets formulated for dogs with renal failure have low protein, phosphate, salt and potassium to reduce the work of the kidneys. An angiotensin converting enzyme (ACE) inhibitor can be administered to reduce blood pressure and reduce the rate of blood proteins passing into the urine. However, despite these treatments, the prognosis remains poor. In one small study of 8 clinical cases, all dogs died within two months of being presented at the veterinary hospital, regardless of treatment (Steward and MacDougall 1984).

Return to top

3. Duration of welfare impact

It is suspected that all or almost all dogs with familial nephropathy will have abnormal levels of proteins present in the urine (proteinuria) before one year of age, with renal failure developing between 6 months and 2 years of age (Lees et al 2014). However, the rate of disease progression varies between individuals, and some dogs can become seriously ill at a more rapid rate than others.  The rate of progression is usually rapid in the late stages of the condition and once abnormally high levels of waste products are found in the blood, the condition usually progresses to the terminal stage within 3 to 6 weeks.

Return to top

4. Number of animals affected

To date, there are no published data available for the number of dogs affected by this condition. Familial nephropathy was reported to have been quite common in Cocker spaniels in the 1980s but the number of dogs affected is said to have since been reduced due to careful screening and breeding programmes. It is reported to affect 11% of English Cocker spaniels in Europe (http://www.antagene.com/en/no/familial-nephropathy-english-cocker-spaniel-breed) but this statistic should be used cautiously because it has no supporting evidence.

The UK Kennel Club has produced a list of carrier dogs, and as of March 2015, there were 20 English Cocker spaniel dogs that were identified as carriers of the FN mutation, versus 2052 dogs that were clear of the mutation. However, this does not give a good idea of the number of dogs affected by the condition, since not all English Cocker spaniels will be registered with the Kennel Club, and not all those registered with the Kennel Club will have been tested.

Return to top

5. Diagnosis

The external clinical signs of familial nephropathy are difficult to distinguish from those associated with other diseases, and an early diagnosis may be difficult to make. In addition, once the signs have been identified, it is not simple to differentiate the different causes of renal disease. For young dogs, persistently high levels of protein in the urine is most often due to familial nephropathy and therefore the best diagnostic tool to start with is urine sampling (Lees et al 2014). Further diagnostic tests include blood chemistry (ie presence of waste products in the blood) and a liver biopsy.

Return to top

6. Genetics

Familial nephropathy is a simple inherited trait which is autosomal (ie not carried on the sex chromosomes thus affects both males and females) and recessive. This means a dog needs to inherit two copies of the mutated gene for it to be affected by the disease. If a dog only has one copy of the mutation, the dog will not be affected but is a carrier, and may pass on the mutated gene to some of their offspring. If two dogs carrying one copy of the mutated gene each are mated together, 25% of their offspring are likely to be affected and a further 50% will be carriers of the condition.

Return to top

7. How do you know if an animal is a carrier or likely to become affected?

Knowledge of the condition in the dog’s family history may highlight whether the dog is a possible carrier or likely to be affected. Simple DNA tests, available in North America and Europe, can be used to identify the mutation for familial nephropathy in Cocker spaniels, with good reliability. DNA can be analysed from either blood samples or mouth swabs. The test can identify dogs that are affected, carriers and clear of the condition.

Return to top

8. Methods and prospects for elimination of the problem

For simple inherited disorders such as familial nephropathy, genetic screening and careful breeding practices are valuable tools to reduce and ultimately eliminate the disease (Farrell et al 2015), and these are ongoing for the breed. DNA tests should be used to identify carriers of the mutated gene in dogs used for breeding. Ideally, dogs that are clear of the condition should be used for breeding. Carriers can be mated with a dog that is clear from the condition, and this will produce non-affected offspring, but the offspring must be monitored for future breeding since some will be carriers of the condition. Mating two carriers, or affected dogs will produce some offspring that are affected by the condition. Many Cocker spaniel breed clubs worldwide now publish a list of carriers and affected dogs for this condition, so that careful breeding practices can be encouraged.

Return to top

9. Acknowledgements

UFAW thanks Dr Emma Buckland (BSc, PhD), Dr David Brodbelt (MA VetMB PhD DVA DipECVAA MRCVS) and Dr Dan O’Neill (MVB BSc, MSc, PhD, MRCVS) for their work in compiling this section.

Return to top

10. References

Chew DJ, DiBartola SP and Schenck PA (2011) Chapter 6: Familial renal diseases of dogs and cats. Canine and Feline Nephrology and Urology, second edition. Eds: Chew DJ, DiBartola SP and Schenck PA. Pages 197-217. Elsevier, Missouri. doi:10.1016/B978-0-7216-8178-8.10006-5

Farrell LL, Schoenebeck JJ, Wiener P, Clements DN and Summers KM (2015) The challenges of pedigree dog health: approaches to combating inherited disease. Canine Genetics and Epidemiology 2: 3. doi:10.1186/s40575-015-0014-9

Krook L (1957) The pathology of renal cortical hypoplasia in the dog. Nordisk Veterinaer-medicin 9: 161.

Lees GE, Helman RG, Homco LD, Millichamp NJ, Hunter JF and Frey MS (2014). Early diagnosis of familial nephropathy in English cocker spaniels. Journal of the American Animal Hospital Association 34: 189–95. doi:10.5326/15473317-34-3-189

Lees GE, Helman RG, Kashtan CE, Michael AF, Homco LD, Millichamp NJ, Ninomiya Y, Sado Y, Naito I and Kim Y (1998). A model of autosomal recessive Alport syndrome in English cocker spaniel dogs. Kidney International 54: 706–19. doi:10.1046/j.1523-1755.1998.00062.x

Lees GE, Wilson PD, Helman RG, Homco LD and Frey MS (1997) Glomerular ultrastructural findings similar to hereditary nephritis in 4 English Cocker spaniels. Journal of Veterinary Internal Medicine 11: 80–85. doi:10.1111/j.1939-1676.1997.tb00077.x

Nowend KL, Starr-Moss AN, Lees GE, Berridge BR, Clubb FJ, Kashtan CE, Nabity MB and Murphy KE (2012) Characterization of the genetic basis for autosomal recessive hereditary nephropathy in the English Springer spaniel. Journal of Veterinary Internal Medicine 26: 294–301. doi:10.1111/j.1939-1676.2012.00888.x

Steward AP and MacDougall DF (1984) Familial nephropathy in the Cocker Spaniel. Journal of Small Animal Practice 25: 15–24. doi:10.1111/j.1748-5827.1984.tb00475.x

© UFAW 2015


Credit for main photo above:

http://depositphotos.com/2163597/stock-photo-cocker-spaniel.html ©Depositphotos.com/cynoclub