Understanding renal dysplasia and why elimination of the RD alleles is necessary for the future health of dogs.

1.  Chronic kidney disease (CKD) is common amongst older dogs and is generally associated with aging. 
There are many reasons for CKD but renal dysplasia is one of them.

2. Renal dysplasia (RD) is a late onset disorder. Most deaths from RD occur in dogs that are
between 5-10 years of age and older. Dogs with up to 40% fetal glomeruli can survive for years
and suddenly die from acute onset kidney failure. The percentage of dogs with one or two
copies of a RD mutation that will die from renal failure as adults is around 3-5%.

Figure 1 shows biopsy data from a pedigree of Lhasa apsos . Most of the dogs in this pedigree have
one or two copies of an RD mutant allele, however they will never show any signs of kidney impairment
because the kidney defect in these dogs is not severe enough to ever affect kidney function. This allows breeders
the opportunity to safely eliminate the RD mutations without disturbing the gene pool. Furthermore, there is
no selective pressure to eliminate these apparently normal dogs so the only way to prevent future clinical
cases of RD is to breed these mutant alleles out of your lines.

3.  The wholesale elimination of dogs that carry one or two RD mutations is never recommended
as this could severely compromise the gene pool and other genetic disorders can emerge. This
is especially true because the mode of inheritance is dominant with incomplete penetrance,
meaning that the extent of the kidney defect is highly variable amongst individuals. For breeding
decisions and use of your test results see:

4. Puppies that die from renal failure due to RD are rare, however these cases are the most
prominent in the scientific literature as this is unusual whereas kidney failure in adults is
common and most likely not be considered as a genetically inherited disorder. This has created
a bias that RD is a juvenile disease.

5. Our RD testing has revealed at least 100 breeds including cross-bred dogs have the RD
alleles. In many of these the frequency of the RD alleles that is greater than 80%. There are
only 3 breeds identified so far with the frequency of the RD alleles is less than 40%. For many
of the breeds there are not sufficient numbers of dogs tested to report the frequency of the RD alleles.

It is important to note that the mechanism of action of the RD alleles is universal and therefore
applies to all breeds. The RD alleles reside within the canine Cox-2 gene. The presence of a RD
mutant allele causes the Cox-2 gene to be chemically modified to varying degrees and this in turn
affects the amount of Cox-2 protein produced by an individual resulting in a wide range of
kidney defects.  The mouse models for RD are strains with mutations in the Cox-2 gene. 
This is reason that this gene was chosen to study in dogs.

Our data suggests that RD is probably the most frequent cause of renal failure in adult dogs.
This is why it is critical to eliminate these alleles from breeding population. In fact a heath

survey published in 2014 by The Kennel Club (UK) lists kidney failure as the 4th leading cause
of death among 5,663 dogs from 179 breeds. The age of onset from this survey was 7-13 years of age,
with a median age of 10 years. The proportion of dogs that died from kidney failure in this survey was 4.22%.

This is consistent with our findings from the RD testing.

6. Unless the RD mutant alleles are eliminated from breeding populations, end stage
kidney failure in canines will continue to plague the future generations of dogs.
Countless adult dogs will have their lives needlessly shortened. Prior to the development of a
genetic test this disease could not be eliminated from breeding stock. Attempts to eliminate RD using
biopsy data has been unsuccessful as even biopsy normal parents can produce RD offspring.

The time to act is now!

Mary H. Whiteley, PhD
DOGenes Inc.