Eliminating the Renal dysplasia mutant alleles from breeding populations
– why breeders must act now for the future health of canines.

In humans chronic kidney disease is often called the “silent killer” because there are no warning signs until
there is a sudden onset of symptoms (acute onset renal failure).  This is also the case in dogs.  Cases of death from
kidney failure from renal dysplasia (RD) are heartbreaking and there is no cure.   Furthermore, this category of death
due to renal failure can be eliminated from breeding populations by breeding out the mutant RD alleles that are genetically
inherited in so many breeds of dogs.

Here is why elimination of the RD alleles is necessary –Points to consider
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 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 (a picture is worth a thousand
words!). Most dogs with one or two copies of an RD mutant allele will never show any signs of
kidney impairment because the kidney defect in these dogs ranges normal to mild to moderate.
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.
Bovee reported similar results for the Shih tzu breed.
"Over a 10 year period 52 matings involving 143 dogs were carried out. The majority of breeding
adults had 0-5% fetal glomeruli. The results did not fit a classical genetic pattern which is not
surprising given the degree of inbreeding in this breed. The mating of dogs with a low
percentage fetal glomeruli (1-5%) did not result in offspring with only low fetal glomeruli.
Some of these matings produced dogs with severe disease. The offspring of matings
from 0% or 1% adults had lower fetal glomeruli but seldom 0% fetal glomeruli. Even the
breeding of 0% adults with each other resulted in offspring with 1-3% fetal glomeruli. An
outcross breeding of a Shih Tzu with 2% fetal glomeruli with a normal Poodle mix
resulted in a litter with all being affected (4-l0% fetal glomeruli). "
Figure 1. is in agreement with the findings of Bovee.
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: https://www.dogenes.com/UseofTestresults.html
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 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 in turn
affects the amount of Cox-2 protein produced by an individual resulting in a wide range of
kidney defects.
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%.
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.

The time to act is now!
Mary H. Whiteley, PhD
DOGenes Inc.