Introduction

In January of 1990, I had my twenty one month old Standard Poodle 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.  The disease is devastating.  Nobody expects to lose a puppy of that age.

After her death, I began searching the literature to discover what was known about JRD in Standard Poodles, including what, if any, research was being done in order to establish the mode of inheritance of this disease in this breed. After finding only one paper in the veterinary literature on juvenile renal disease in Standard Poodles (1), and discovering that no one was currently working on this problem,  I  began a collaboration with George Padgett, DVM, geneticist and Professor of Pathology at Michigan State University.   Our objective is to establish the mode of inheritance of JRD in Standard Poodles,  and an eventual open registry at the Institute for Genetic Disease Control in Animals (GDC), in Davis, California.  Using an open registry,  breeders who wish to can reduce the incidence of this disease, if not breed it out entirely.

The information I have gathered since then leads me to believe that most individual cases of JRD are treated by owners and veterinarians as isolated occurrences rather than as the manifestation of a genetic disease.  If the 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 again treated as an isolated incident.  Unless there are multiples in a litter it goes largely unrecognized, and no recognition is made nor thought given to those littermates who are carriers.

Symptoms

Early symptoms of juvenile renal disease include a mild to moderate increase in water consumption, and frequency of urination, as well as 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, loss of appetite, 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.

In Standard Poodles with JRD, also known as renal dysplasia, symptoms may be noted as early as a few weeks after birth;  and affected puppies are almost without exception symptomatic before two years of age.  Some puppies fail to thrive: most grow normally until symptoms appear.  Puppies with renal dysplasia may appear clinically normal for extended periods of time before developing signs of chronic renal failure.  The rate at which renal

dysplasia progresses to overt renal failure depends on the severity of the initial renal lesions. Dogs commonly do not exhibit clinical signs of renal failure until less than 25% of renal function remains.  A dog with renal dysplasia affecting only one kidney may be symptom free, and the dog may live a normal lifetime.

Diagnosis

If a Standard Poodle under two years of age is found to have an elevated BUN (blood urea nitrogen) and creatinine, and significant protein in the urine, as indicated by an increased urine protein:creatinine ratio,  JRD should be strongly suspected.  Abdominal palpation by a veterinarian may reveal small irregularly shaped kidneys.  An ultrasound can be a useful diagnostic tool, since the kidneys are often atrophied and underdeveloped. It must be kept in mind, however, that kidneys from affected dogs may be normal size.

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.   The slides should be examined by an experienced pathologist.  There are a number of pathologists who have a considerable interest in this disease.   A biopsy or autopsy of a puppy less than two months of age would not be fruitful,  since the normally immature kidneys could not be distinguished from those affected by JRD.   It is not reasonable to expect that a puppy owner who is not a breeder would agree to a wedge biopsy, because the results of the biopsy would not change the treatment or prognosis, and because anesthesia is not without risk.

Management

If the reduction in renal function is identified early, when only an increase in water consumption and frequency of urination are evident, medical management can be instituted immediately.  Although the renal damage is not reversible, the quality and length of the patient's life may be improved  considerably by early treatment.

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 increasing comfort and extending life, since high phosphorus accelerates renal failure, and restricted phosphorus slows it down.   K/D is low in phosphorus, as well as protein, 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. Some veterinary schools are  performing organ transplants, but transplanted kidneys in dogs are commonly rejected, and involve an extraordinary expense and commitment.

These treatments are palliative at best, and the prognosis for JRD is grim. Puppies usually die within several months of being diagnosed, almost always before age two.  I  am, however, following the progress of two dogs who have JRD with less severe kidney involvement, and who are being well maintained on low protein and low phosphorus diets.  These dogs are now both more than three years old, and both were diagnosed before they were

symptomatic.   One was tested because five of his littermates died of JRD, and one because his veterinarian was giving free BUN tests to her clients along with heartworm checks.  These two dogs are an exception in my experience with JRD in this breed.  Although they are doing well, ultrasound has revealed that their renal disease affects both kidneys.

Because no effective treatment for JRD exists, the most promising approach for dealing with it is for clinical veterinarians, owners and breeders to understand its genetic basis. When veterinarians are aware of genetic diseases in specific breeds,  and of ongoing research in these genetic diseases in specific breeds, they can direct breeders and owners of dogs affected by these diseases to the people researching them.  Every puppy who comes to our attention, adds to the data in our research database.  If the mode of inheritance can be determined using litter data from puppies already born, it may not be necessary to breed test litters, or it may be possible to breed fewer test litters.

Genetics

Dr. Padgett told me that in most of the breeds in which JRD has been studied, it is a simple (one gene), autosomal (not sex linked),  recessive (both parents have to carry the gene) disease.  In some breeds, it may be a recessive with incomplete penetrance, which could account for variation in expression from generation to generation, or litter to litter. The presence of just one affected puppy determines that both parents are carriers. Littermates of an affected puppy have a 67% chance of being carriers. Aunts, uncles, and grandparents of an affected puppy have a 50% chance of being carriers.

A sire who has produced an affected puppy is a defined carrier.  If the same sire has been bred to bitches who produced sizable litters with no affected puppies, those bitches have proven themselves to be probably clear.  This is referred to as retrospective test mating.  "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 a 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's book,  Genetics of The Dog. (2)   Even if only the sire or dam of a litter is a carrier, the other parent being clear, an average of 50% of all their puppies are carriers themselves.   If the cause of JRD is polygenic, several genes would be necessary collectively  in order for the disease to occur.

We have been tracking a large number of affected litters, and the number of JRD puppies within them.  Dr. Padgett informed me in March, 1996,  that using the Chi-square statistical test on the data I have collected, the data is consistent with JRD in Standard Poodles being a simple autosomal recessive disease at the 97.5% level of significance.   It may be a simple recessive disease with incomplete penetrance.   It is possible that as more data is collected, the conclusion about the specific mode of inheritance may change.

The mode of inheritance of Juvenile Renal Disease can be established from information about the number of puppies born in a large number of affected litters and the number of puppies in those litters who are affected by JRD. In addition to the litter data, we need data from a veterinarian which confirms the diagnosis of juvenile renal disease.  Lab reports, biopsy results or autopsy reports are all acceptable.  If we have this pedigree data from a sufficient number of litters, more than one test litter may not have to be deliberately bred to determine the mode of inheritance.  Nobody wants to breed a test litter if the information needed can be obtained in some other manner.

Dr. Padgett noted that with perhaps as few as six additional accurately diagnosed litters which are already in existence or with one or two test matings of proven carriers, the data will become sufficiently robust to be publishable in any of a number of scientific journals.  (3)

Genetic Research

Michigan State University has a large grant to be used in actual gene marker research.  Dr. Padgett assured me that JRD, also called familial renal disease and renal dysplasia, is one of the first diseases that will be studied because it is  prevalent in so many breeds, it appears at an early age and it is  always fatal.  If Standard Poodle breeders don't have the autopsy and pedigree data available and collected in a one location, Standard Poodles  will not be among the breeds studied.  It is important to be one of the breeds in the actual study since the genetic mode of inheritance of this anomaly is different in different breeds.

VetGen has a grant to find the gene marker(s) for the juvenile renal disease, very similar to that in Standard Poodles,  seen in Soft Coated Wheaten Terriers.  This was a high priority for SCWT breeders, who organized in order to pay for the research to be done to identify carriers of this disease before they are unknowingly bred.  VetGen contacted me in July of 1996, to find out whether DNA samples,  using cheek swabs, could be obtained from families of Standard Poodles in which this disease has occurred.  The Dog Genome Project at the University of California, Berkeley, is also working on finding the gene marker(s) for juvenile renal disease in Soft Coated Wheaten Terriers, after being contacted by, and receiving support and a high level of cooperation from SCWT breeders.  If Standard Poodle breeders and owners want the gene marker(s) for juvenile renal disease in their breed to be found, they are going to have to become more proactive.

If you would like to participate in this research project, and have information pertinent to juvenile renal disease in Standard Poodles, no matter how old, please contact Susan Fleisher, 2112 Eunice Street, Berkeley, CA 94709, USA. phone: 510 527-0793 e-mail: slfleisher@iname.com or slfleis@concentric.net

Author Susan L Fleisher, slfleisher@iname.com, or slfleis@concentric.net. Copyright 1996, all rights reserved.  A more detailed article on juvenile renal disease in standard poodles, written for veterinarians may be found at http://www.oocities.org/Heartland/Plains/3596/jrd.html

This article is Copyright 1997 by the Author.  It may NOT reside at another website (use links, please) other than the URL listed above without the permission of the Author. This article may not be sold for profit nor incorporated in other documents without the Author's written permission and is provided "as is" without express or implied warranty.

References

1.  DiBartola S.P., Chew D.J., et al:  Juvenile renal disease in related Standard Poodles. JAVMA:183:693-696.

2.  Willis, Malcolm B: Genetics of the Dog. Howell Book House, New York, NY, 1989;p 356.

3.  Poodle Variety, Santa Barbara, CA, February-March 1996, pp 88-89.

References to information about Juvenile Renal Disease in the Veterinary Literature:

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:pp1796-1801.

Hoskins Johnny D:The Kidneys, Congenital and Inherited Disorders.Veterinary Pediatrics dogs & cats from birth to 6 months. W.B. Saunders, Philadelphia, Pa, 1990: pp272-276.

Willis, Malcolm B: Genetics of the Dog. Howell Book House, New York, NY, 1989;p356.

Cowgill, L.D.: Diseases of the Kidney.  Textbook of Veterinary Internal Medicine (S.J.Ettinger, ed.). W.B. Saunders, Philadelphia, Pa, 1983: pp 1793-1879

Susan Fleisher
Berkeley, CA

slfleis@concentric.net
slfleisher@iname.com