In January of 1990, I had my twenty-one month old Standard Poodle puppy put down. She was one of three puppies in a litter of eleven to die of Juvenile Renal Disease (JRD). All three of the puppies with the disease appeared healthy and grew normally until clinical signs appeared at ten months in one, and twenty months in the other two. She died two weeks after being diagnosed.
The disease is devastating. The prognosis is dismal. Nobody expects to lose a puppy of that age. I have been collecting information since her death on the disease that killed her.
Breeds Affected by Juvenile Renal Disease
Despite the fact that several articles on Juvenile Renal Disease and Familial Renal Disease were published in veterinary journals in the 1970s, and many others have been published since that time on JRD in Dobermans Pincers, Alaskan Malamutes, Norwegian Elkhounds, Samoyeds, Standard Poodles, and Golden Retrievers, most individual cases of JRD are treated by owners and veterinarians as isolated occurrences rather than as the manifestation of a genetic disease. The type of renal disease, also called Renal Dysplasia, from which my puppy died, is also seen in Airedale Terriers, Bedlington Terriers, Boxers, Bulldogs, Chow Chows, Great Danes, Great Pyrenees, Irish Wolfhounds, Keeshonds, King Charles Spaniels, Miniature Schnauzers, Old English Sheepdogs, Swedish Foxhounds, Shih Tzus, Lhasa Apsos, Soft Coated Wheaten Terriers, Portuguese Water Dogs, and Yorkshire Terriers. It is just recently being seen in Golden Retrievers, a breed in which it had not before been recognized.
Other types of genetic renal disease are also well known in Rottweilers, Shar Peis, Miniature Poodles, Cairn Terriers, Welsh Corgis, Pekingese, Shetland Sheep Dogs, Collies, Beagles, Basenjis, Bull Terriers and Cocker Spaniels, among others. Similar forms of genetic renal diseases may have different modes of inheritance in different breeds.
Early symptoms of Juvenile Renal Disease include drinking copious amounts of water, something that might not be readily apparent in a house with more than one dog, frequent urination, and dilute urine which has little color or odor. Some affected puppies leak urine, many do not. Often a puppy owner's earliest complaint is about the difficulty of housebreaking a puppy later discovered to have JRD. The volume of water consumed, and, in some puppies, leakage of urine can make housebreaking a formidable task. As the disease progresses, vomiting, weight loss, anorexia, lethargy, and muscle weakness are seen. There is sometimes a chemical odor to the breath as a result of metabolic waste not being excreted by the kidneys.
If the reduction in renal function is identified early, when only increased water consumption and urination are evident, medical management can be instituted immediately. Although the renal damage is not reversible, the quality and length of the puppy's life may be improved by early treatment.
The most accurate method for diagnosing JRD is a wedge biopsy from one kidney taken any time after the second month of life, or a histopathologic exam after death. A biopsy or autopsy of a puppy less than two months of age would not be fruitful, since the normally immature kidneys cannot be distinguished from those affected by JRD. The slides should be examined by an experienced pathologist. There are a number of pathologists who have a considerable interest in this disease. It is not reasonable to expect most puppy owners who are not breeders to agree to a wedge biopsy, since a more accurate diagnosis will not affect the treatment or prognosis, and since the necessary anesthesia is not without risk.
Treatments for the symptoms of JRD include a low protein prescription diet, such as Hill's K/D. The predominant effect of the low protein diet is to minimize production of uremic toxins so that the patient feels better. Low protein diets may help extend life in dogs. Phosphorus is more important in this regard, since high phosphorus accelerates renal failure, and restricted phosphorus slows it down. K/D is low in phosphorus, so it remains a good food for dogs in this condition.
In addition to diet, IV fluids can be administered to correct disturbances created by the retention of uremic toxins. Epogen can be prescribed to treat the anemia of chronic renal failure, resulting in improving the quality, and probably the length of life. Some veterinary schools are performing organ transplants, but transplanted kidneys in dogs are commonly rejected, and involve an extraordinary expense and commitment.
Recognizing the Problem
If a breeder is informed about a medical problem in a puppy she has sold, and often she is not, or, if just the owner of the dam is informed, and it is only one puppy in a litter about whom she is informed, it is usually treated as an isolated incident. Unless there are multiples in a litter, and the breeder is informed about each, the fact that the illness from which a puppy is suffering is a genetic disease is not recognized, and no recognition is made nor thought given to those littermates who are carriers.
Without an understanding of the genetics involved, and most veterinarians treat isolated incidences as being from an unknown cause rather than as Juvenile Renal Disease, veterinarians are unable to offer counseling to breeders, and more and more carriers are unknowingly bred. In the breeds in which JRD is known to occur many of the puppies who fall into the "fading puppy syndrome" and die at a young age may have died of JRD. Many stillborn puppies are victims of this disease. Often, however, an affected puppy will grow normally until it is between ten and twenty four months of age before it is symptomatic, diagnosed and dies.
George Padgett, D.V.M., a geneticist and professor of pathology at Michigan State University, told me that JRD affects about 20 breeds. In most of the breeds in which it has been studied it is a simple (one gene), autosomal (not sex linked) , recessive (both parents have to carry the gene), disease.
Both parents of an affected puppy are therefore defined carriers. The presence of just one affected puppy determines that both parents are carriers. Littermates of an affected puppy have a 66% chance of being carriers. Aunts and uncles of an affected puppy have a 50% chance of being carriers, as do grandparents.
According to Dr. Padgett, if a sire has produced an affected puppy, and is therefore a defined carrier, he has also proven bitches who are probably clear: those bitches who when bred to him have produced sizeable litters in which there were no affected puppies. "Proven" is used rather loosely here, since statistically a dog mated to a carrier and producing six normal offspring would still have a 17.8% chance of being carrier. Twelve normal offspring would reduce that chance to 3.17%. The preceding figures which refer to simple autosomal recessive anomalies are from Malcolm B. Willis' book, Genetics of The Dog. If the disease is caused by a simple autosomal recessive gene, both parents must be carriers of the gene to produce an affected puppy.
However, even if only the sire or only the dam is a carrier, the other parent being clear, approximately 50% of all the puppies born are carriers themselves. If the cause of JRD is polygenic, several genes would be necessary collectively in order for the disease to occur. In Samoyeds the mode of inheritance is now known to be x-linked recessive. In that breed, only males are affected with the disease, but females pass it on through the x chromosome.
Among the pedigrees I have collected are those of 25 litters of an American Champion sire. There are a large number of American Champions among his offspring. In two of these litters there was one puppy with JRD. The sire is therefore a carrier, and approximately half of the puppies in every one of his litters are carriers. This is just one sire: the arithmetic is stunning. The possibility that this will not eventually touch every breeder in the breeds in which it is known is unlikely, and, by the time it does, it will be difficult if not impossible to eliminate.
In order for Juvenile Renal Disease, sometimes called Familial Renal Disease, Renal Dysplasia, or Congenital Hypoplasia to be studied in any breed, several things have to occur. Breeders should be informed by owners of any puppy who is found to be affected, or who dies of renal disease at a young age. The breeder should contact the owners of the other puppies in the litter, so that they can be tested.
Bloodwork should be done to look for elevated blood urea nitrogen (BUN), and urine tested to establish a urine protein:creatinine ratio. Unaffected litter mates should all be considered carriers, since there is no way at this time to distinguish a carrier from a non-carrier puppy. The only positive outcome of having an affected litter that I can think of is that it enables the breeder to identify carriers and potential carriers. Every affected litter has the potential to stop carriers from producing more carriers. If an autopsy shows that a puppy did not die of JRD, that is also useful information. I realize that post mortem examinations are expensive, though a restricted exam to look for one specific finding would be much less expensive. Once carriers and dogs who are clear have been identified, concerned and careful breeders can work to systematically breed the disease out.
George Lees, DVM of Texas A M University is currently doing research on Juvenile Renal Disease in Cocker Spaniels. Both VetGen, in Michigan, and the Canine Genome Project at the University of California, Berkeley, are searching for the gene marker(s) for the Juvenile Renal Disease seen in Soft Coated Wheaten Terriers.
The Department of Human Genetics at Michigan State University has a large grant to be used in gene marker research. The initial effort will be to develop 400 DNA probes in order to saturate the dogs' chromosomes with the probes. After the probes have been established, screening can begin for linkage of any dog disease gene of interest. Eventually, the benefits will be that dogs will be able to be screened for the carrier state of the gene. This research will not be completed for many years.
In the meantime, since the funding is sufficient only to develop the probe system and not to study any particular disease, funding will have to be provider by breeders themselves or by other outside sources for the study of specific disease gene projects. For the first few individual studies, the estimate is that the cost will run from $25,000 to $50,000 to screen through the 400 probes to establish a close linkage.
In order to carry out screening for linkage for this or any other genetic disease, pedigrees of 15-20 litters in which there are at least two affected and two unaffected puppies must be identified. Blood samples from at least two affected puppies and two unaffected puppies in each litter, as well as from both parents have to be available for study. Puppies from a repeat breeding are considered littermates for this purpose. The blood samples can, of course, be stored for future use.
Although progress is being made, waiting for DNA testing to become readily available is not a feasible solution to the problems of many genetic diseases. Selectively breeding away from carriers now is the only responsible action. In some instances, careful breeders have succeeded in largely eradicating some genetic disorders from their breeds. Success depends on a number of factors. Every puppy buyer must be encouraged to report any major illness back to the breeder. Breeders must have a clear understanding of the modes of transmission of genetic disorders that affect their breeds. Known carriers as well as possible carriers, (littermates and offspring of those discovered to be carriers) must be conscientiously kept out of the gene pool, or used very judiciously. A method of communication among breeders must be established.
Clearly, an open registry such as the open registry begun in July, l992 for Sebaceous Adenitis in Standard Poodles (this disease also occurs in other breeds) is an important step forward and an invaluable resource. Open registries as well as research databases in many canine diseases are being established at the Genetic Disease Control For Animals (GDC) in Davis, California. In Europe, open registries have made it possible for careful breeders to greatly reduce the number of cases of some genetic disorders.
An open registry would include the names of carriers of the disease as well as the names of dogs who are clear, those who when bred to a carrier did not produce any cases of the disease in a litter of significant size. Obviously, the early onset of Juvenile Renal Disease allows carriers to be identified much sooner than does a disease which manifests itself later in life.
Malcolm B. Willis wrote in his introduction to Genetics of the Dog, "We are the custodians of our chosen breeds during the relatively short period of our dog breeding lives. It behoves us to hand over the material we breed with in a better state than when we received it or we have achieved nothing and the breeds we profess to love will be the sufferers. .........."
A "Problem Specific Data Base for Renal Failure in Immature Dogs" is included in the chapter on renal disease in Veterinary Pediatrics, Dogs Cats from Birth to Six Months, 2nd edition, as is a table on "Medical Management of Chronic Renal Failure".
Kruger, J.M., Osborne, C.A., et al. : Congenital and Hereditary Disorders of the Kidney. Veterinary Pediatrics Dogs Cats from Birth to Six Months., 2nd edition. (J.D. Hoskins, ed.) W.B.Saunders, Philadelphia, Pa, 1995: pp 401-406.
DiBartola Stephen P. et al: Familial Renal disease in Dogs and Cats. Textbook of Veterinary Internal Medicine. (S.J. Ettinger, E.C. Feldman, ed) W.B. Saunders, Philadelphia, Pa. 1995:pp 1796-1801.
Willis, Malcolm B: Genetics of the Dog. Howell Book House, New York, NY, 1989; p 356.
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