Renal Dysplasia Testing

Kidney disease in dogs is often not apparent until the kidneys begin to fail. Unless owners are aware of a breed predisposition to kidney disease, they are likely to miss signs of increased drinking and urination. Even vomiting, weight loss and anorexia — other signs of IBD — can be mistaken for other health conditions.

Renal dysplasia (RD), a potentially fatal canine kidney disease, is especially difficult to recognize because affected dogs may never show the classical signs and others may appear normal for years. Meanwhile, carriers — dogs that pass the gene mutation to their offspring but may not be affected themselves — continue to be bred, thus proliferating the disease throughout a breed.

Though it is not known exactly how widespread renal dysplasia is, the disease affects several breeds including Alaskan Malamutes, Boxers, Doberman Pinschers, Great Danes, Great Pyrenees, Portugese Water Dogs and Samoyeds. The disease also occurs in many other breeds.

Until recently, veterinary clinicians and scientists presumed that renal dysplasia was a disease affecting dogs less than 2 years of age, which explains why for many years it was known as juvenile renal dysplasia. Research over the past decade in Lhasa Apsos showed otherwise.

“We were following a pedigree of Lhasa Apsos over a 10-year period and because the biopsy results were so varied, we found that this disease is not limited to dogs under 2 years old,” says Mary Whiteley, Ph.D., scientific director of DOGenes in Ontario, Canada. “In fact, more adults die from this disease later in life. Dogs with kidney disease can live up to 10 years before dying from kidney failure.”

The classic features of renal dysplasia are seen microscopically in pea-sized kidney tissue taken from a wedge biopsy. The telltale sign is underdeveloped glomeruli, the knotted-looking capillaries in the kidneys that filter blood. During embryogenesis, the kidney fails to develop normally, causing fetal glomeruli. The amount of fetal glomeruli indicates the severity of disease.

All dog breeds affected by renal dysplasia have this common phenotype. The condition is considered congenital because it is present from birth. It also is inherited. Sadly, there is no cure for the disease, although treatment can help improve a dog’s quality of life.

Whiteley identified the RD gene mutation in 2007 through her work studying the disease in Lhasa Apsos and Shih Tzu. The mode of inheritance is dominant with incomplete penetrance, meaning a dog carrying the mutation may not show clinical signs of disease but can still pass it on to the next generation.

Now, a direct DNA test is available for all breeds of dog. “It’s not a surprise that the mutation is consistent throughout different breeds,” Whiteley says. “It probably existed long before there were breeds.”

A Mislabeled Juvenile Condition
The mislabeling of renal dysplasia as a juvenile condition has contributed to confusion about the disease. “The term ‘juvenile’ has led many breeders to think that renal dysplasia isn’t a problem in their kennels, because they don’t realize that the condition can affect older dogs,” Whiteley says.

The genetic test has helped to provide definitive answers whether dogs being considered for breeding are carriers, affected or clear from disease. Breeders can apply the knowledge to their breeding programs and continue to breed quality individuals without re­ducing genetic diversity.

Before the genetic test was available, breeders risked spreading RD through their bloodlines because there was no way to know a dog’s genetic health status. Presenting “Renal Dysplasia in Shih Tzu Dogs” at the 28th World Congress of the World Small Animal Veterinary Association in October 2003 at Bangkok, Kenneth Bovee, D.V.M., emeritus professor at the University of Pennsylvania, addressed the potential rapid spread of the disease if left unchecked.

Over 10 years, Bovee followed the offspring of 52 matings from 13 Shih Tzu, showing that the majority of breeding stock had some level of fetal glomeruli. The prevalence of the defect in Shih Tzu was estimated around 85 percent, yet actual clinical cases represented a low percentage. Before the mutation was discovered by Whiteley, Bovee speculated that the disease had a dominant with incomplete penetrance mode of inheritance.

“The development of a genetic test is imperative to control this disease in this breed as well as others,” he advised. “Dogs with a low percentage of fetal glomeruli can produce puppies with renal disease, and even the breeding of adults with no fetal glomeruli can result in offspring with 1 to 3 percent fetal glomeruli. The apparent low incidence of disease is a danger to the breeding population, as seemingly normal adults can go undetected and produce clinically affected offspring.”

The subtle signs of renal dysplasia also help to mask the disease. Vomiting, weight loss, anorexia, lethargy and muscle weakness can also be seen in healthy dogs and puppies. Other signs of RD are selective appetite, poor hair coat and dilute urine with little color or odor. Secondary urinary tract infections may occur.

Affected puppies may leak urine, which owners sometimes misinterpret as a house-training problem. A chemical odor may be detected in the breath due to metabolic wastes not being properly excreted by the kidneys.

“In my experience, dogs first present with increased drinking and urination,” says Jerold Bell, D.V.M., clinical associate professor of genetics at Tufts University Cummings School of Veterinary Medicine. “They all have dilute urine, with an inability to fully concentrate their urine. They may or may not spill protein into their urine.

“Different dogs with this disease, even dogs within the same litters, can present differently. Some dogs die young in renal failure, while others live many years before succumbing to renal failure in middle or old age. These dogs may show no signs of renal disease until their kidney systems are too compromised to compensate for diminished function.”

A Dominant Condition
No one knows why the RD gene mutation causes severe disease in some dogs and mild or no indication of disease in others. What is known is that only one mutant copy of the gene is sufficient to cause disease. The disease can be inherited from one carrier parent, but this parent may not show signs of the disease. However, all dogs that have the RD mutation can pass the mutation and possibly the disease on to their offspring.

“On average, a dog with the mutation will pass it on to about half of his or her offspring, but only about 5 percent of dogs with the mutation will be clinically affected with the disease,” Whiteley says. “Dominant genes are usually easy to breed against because the genotype is clear before the dog reaches breeding age; however, because of the incomplete penetrance of RD, this results in the low disease occurrence rate in which breeders unknowingly could use carriers in their breeding programs.”
The mode of inheritance was debated for many years because of the range of signs and pathological findings associated with the disease. “The wide variety of clinical manifestations and complex nature of this disease have been poorly understood for years,” Whiteley says. “The key thing for breeders to keep in mind is that even though no clinical signs of the disease are present, the mutation can still be passed on to offspring.”

Although the genetic test is primarily a tool for breeders, it also can be used to provide a definitive diagnosis of renal dysplasia, offering a less-invasive test than the surgical wedge biopsy. On the other hand, the DNA test does not provide information about the severity of disease, whereas the wedge biopsy does.

Renal dysplasia can be challenging to diagnose partly because affected dogs may appear clinically normal for many years before developing signs of chronic renal failure. The age of onset ranges from 4 weeks to 5 years of age, but in many cases, dogs are even older. Since some affected dogs never show signs, they are likely to stay in a breeding population.

Veterinarians generally recommend any dog of a breed known to have an RD predisposition that is under 2 years of age and has elevated kidney enzymes and increased protein in the urine should be tested for renal dysplasia. Though the rate of disease progression varies in individual dogs, in most cases, clinical signs do not appear until 70 to 75 percent of the kidney is nonfunctional.

Whether renal dysplasia is determined using a wedge biopsy or DNA testing, breeders and owners may begin treatment sooner when dogs are known to have the condition. Not unlike treatment recommended for any type of chronic renal failure, dogs with renal dysplasia should be fed a diet with a lower quantity of a high-quality protein and low phosphorus. Excess or crude proteins increase the waste products that the kidney has difficulty eliminating from the body. Reduced phosphorus clearance through the kidneys also contributes to a lack of appetite.

Once the disease progresses and the dog’s kidneys can no longer clear the waste products on their own, regular fluid therapy can be given to help flush out the waste products and make a dog comfortable. Although renal dysplasia is not curable or reversible, the quality and length of a dog’s life may be improved by early detection and treatment.

The good news for breeders is that a genetic test is available to determine a dog’s genetic health status. Impor­tantly, carriers with valuable breed characteristics do not have to be eliminated from a breeding program. By breeding against the condition, breeders can eventually eliminate the disease without reducing genetic diversity.

CREDIT: Used with permission from the Purina Pro Club Update newsletter, Nestle Purina PetCare