Subject: rec.pets.dogs: Juvenile Renal Disease
From: [email-masked] (Susan L Fleisher)
Date: 17 Apr 2004 11:27:26 GMT
Newsgroups: rec.pets.dogs.info,rec.answers,news.answers

Archive-name: dogs-faq/medical-info/JRD
URL: http://www.k9web.com/dog-faqs/medical/JRD.html
Last-modified: 07 Nov 1997

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                           Juvenile Renal Disease
                                      
Author

   Susan L. Fleisher, [email-masked]. Copyright 1996, all rights
   reserved.
   
Table of Contents

     * Introduction
     * Symptoms
     * Recognizing the Problem
     * Heritability
     * Eliminating JRD
     * References
       
     _________________________________________________________________
                                      
Introduction

   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. 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.
   
   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 Pinchers, Alaskan Malamutes, Norwegian Elkhounds and
   Samoyeds as well as in Standard Poodles, most individual cases of JRD
   are treated by owners and veterinarians as isolated occurrences rather
   than as the manifestation of a genetic disease. The disease is also
   well known in Rottweilers, Shiz Tsus and Lhasa Apsos, and is seen in
   Soft Coated Wheaten Terriers, Portuguese Water Dogs, Shar Peis,
   Miniature Schnauzers, and Cocker Spaniels, among others. It is now
   being seen in Golden Retrievers, a breed in which it had not before
   been recognized.
     _________________________________________________________________
                                      
Symptoms

   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 will leak urine,
   others won't. As the disease progresses, vomiting, weight loss,
   anorexia, lethargy, and muscle weakness are seen. There is often a
   chemical odor to the breath, and teeth are sometimes discolored. Some
   puppies grow normally until they are diagnosed, and some appear as
   failures to thrive.
   
   Treatment for JRD consists of a low protein prescription diet, Hill's
   K/D, and, in addition, IV fluids can be given to act as a kind of
   dialysis. Epogen, an expensive drug which needs to be carefully
   monitored, can be also be given to treat the hypoproliferative anemia
   of chronic renal failure. Some Veterinary schools are experimenting
   with kidney transplants, but transplanted kidneys in dogs are commonly
   rejected.
   
   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 do know of several dogs who have JRD with less severe kidney
   involvement, and who are being well maintained on low protein diets.
   These dogs are both more than three years old, and were diagnosed
   before they were symptomatic. One because his litter was decimated by
   the disease, and one because his vet was giving free BUN tests to
   his/her clients.
     _________________________________________________________________
                                      
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 well 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.
     _________________________________________________________________
                                      
Heritability

   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 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 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' 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, 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.
     _________________________________________________________________
                                      
Eliminating JRD

   Among the pedigrees I have collected are those of twenty five 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 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 of breeds affected
   by this disease should have any stillborn pups and all pups who die
   before being sold, autopsied, if only to look for this one disease. If
   the puppy is seen to have JRD, (the kidney cells actually have to be
   studied under a microscope, since occasionally the kidneys appear
   normal to the naked eye), the rest of the litter can be tested.
   Bloodwork should be done to look for an elevated BUN, and urine tested
   to establish a urine protein creatinine ratio. Unaffected litter mates
   should all be considered carriers, since there is no way 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. I can assure anyone that is infinitely
   more expensive on an emotional as well as a financial basis not to
   have an autopsy done to look for this disease. 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
   reasearch on Juvenile Renal Disease in Cocker Spaniels. The Soft
   Coated Wheaten Terrier Club of America is sponsoring research by Dr.
   Shelley Vaden at the North Carolina State University College of
   Veterinary Medicine. Dr Vaden is collecting health records on SCWT,
   and she has established a breeding colony.
   
   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. Several other universities, such as
   Texas A & M and the University of California at Berkeley are involved
   in DNA research also.
   
   Waiting for DNA testing to become readily available is not a feasible
   solution to the problems of 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. 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. Registries in many canine
   diseases are being established at the GDC (Genetic Disease Control) 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."
     _________________________________________________________________
                                      
References

   Contributed by Maria Unson, [email-masked]
     * Thomas DA.
          + Juvenile renal disease in a dobermann [letter].
          + Veterinary Record, 1984 Oct 27, 115(17):446-7.
            
     * DiBartola SP; Chew DJ; Boyce JT.
          + Juvenile renal disease in related Standard Poodles.
          + Journal of the American Veterinary Medical Association, 1983
            Sep 15, 183(6):693-6.
          + Abstract: Chronic renal failure was diagnosed in 6 young
            Standard Poodles from 2 related litters. Clinically, the
            disease was characterized by polydipsia, polyuria, anorexia,
            lethargy, vomiting, and bony deformities suggestive of
            fibrous osteodystrophy. Laboratory evaluation revealed
            azotemia and hypercholesterolemia in all 6 dogs and
            nonregenerative anemia in 3 dogs. Two dogs had
            hyperphosphatemia and another 2 were hypercalcemic.
            Isosthenuria and proteinuria were found in both dogs for
            which urinalyses were available. The kidneys were
            characterized pathologically by interstitial fibrosis,
            variable interstitial infiltrates of lymphocytes and plasma
            cells, tubular atrophy, tubular dilatation, tubular basement
            membrane mineralization, cystic glomerular atrophy, and
            immaturity of glomeruli, with inconspicuous capillary lumens.
            
     * Chew DJ; DiBartola SP; Boyce JT; Hayes HM Jr; Brace JJ.
          + Juvenile renal disease in Doberman Pinscher dogs. Journal of
            the American Veterinary Medical Association, 1983 Mar 1,
            182(5):481-5.
          + Abstract: Renal failure was diagnosed in 22 young Doberman
            Pinscher dogs. The clinical findings were anorexia, weight
            loss, vomiting, lethargy, polydipsia, polyuria, and
            dehydration. Laboratory findings were azotemia,
            hyperphosphatemia, lymphopenia, nonregenerative anemia,
            hypercholesterolemia, and proteinuria. The kidneys were
            characterized pathologically by glomerular sclerosis, cystic
            glomerular atrophy, tubular dilatation, tubular atrophy,
            mononuclear interstitial inflammation, interstitial fibrosis,
            interstitial mineralization, and hyperplasia of the
            collecting duct epithelium.
            
     * Picut CA; Lewis RM.
          + Juvenile renal disease in the Doberman Pinscher:
            ultrastructural changes of the glomerular basement membrane.
            Journal of Comparative Pathology, 1987 Sep, 97(5):587-96.
          + Abstract: Ten cases of juvenile renal disease in Doberman
            Pinschers were examined by light microscopy and 8 of them
            additionally by electron microscopy. Two distinct basic
            ultrastructural lesions of the glomerular basement membrane
            (GBM) were observed. One is characterized by lamellation of
            the lamina densa with intramembranous focal areas of lucency
            containing electron-dense particles, the second by diffuse
            attenuation of the lamina densa with intramembranous and/or
            subendothelial deposition of matrix entrapping cross-banded
            fibres (collagen). Based on similar ultrastructural changes
            in other hereditary nephropathies in man and dogs, a
            metabolic or biochemical basis for the structural lesions is
            suspected.
            
     * Rosenbruch M., [Pathomorphology of so-called juvenile renal
       disease in the dog].
          + Zentralblatt fur Veterinarmedizin. Reihe A, 1986 Mar,
            33(3):193-207. Language: German.
       
     * Morton LD; Sanecki RK; Gordon DE; Sopiarz RL; Bell JS; Sakas PS.
          + Juvenile renal disease in miniature schnauzer dogs.
            Veterinary Pathology, 1990 Nov, 27(6):455-8.

     _________________________________________________________________

    Juvenile Renal Disease
    Susan Fleisher, [email-masked]
    
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