Protein-Wasting Diseases: What To Look For
Meryl Littman VMD DACVIM
University of Pennsylvania School of Veterinary Medicine Published in Benchmarks, yyyy.

During the last decade, we have recognized that some Soft Coated Wheaten Terriers have a genetic predisposition for two protein-wasting diseases, namely protein-losing nephropathy (PLN) and protein-losing enteropathy (PLE). we have traced the pedigrees of more than 40 afflicted dogs and found them to be closely related. Although the exact mode of inheritance is not understood, it would be wise not to inbreed and not to breed close relatives of afflicted dogs. In addition to the genetic predisposition, are there any environmental stimuli which may induce the onset of these diseases? The biopsy results of the organs involved (the kidney in the case of PLN, the intestines in the case of PLE, indicate inflammatory infiltration such as expected with immune-mediated disease. Are there certain substances (antigens) which "turn on" the immune-mediated response? Although there is no proof yet the influence of certain factors such as allergies to food, viral, or bacterial proteins needs to be studied. It is interesting that many Wheatens are presented to the veterinarian for dermatologic problems (face rubbing, paw chewing) and are diagnosed as having atopy, or the skin manifestations of allergies, usually inhalants but sometimes from food allergies. Are allergic SCWT dogs more or less affected by protein-wasting diseases? What hormonal influences are there in the manifestations of the protein-wasting diseases? What differences are there in the immune system of the sexes which might allow females to be more vulnerable (see below)? As you can see, there are many questions which need to be addressed. One of the big problems we have in dealing with these particular inherited diseases is that the onset of clinical signs or symptoms is often not until the dog is middle-aged. Thus, the afflicted dogs may already have been used for breeding. Also, there is no special screening test to assure us that certain (young) dogs are safe for breeding. The following tests described below to look for protein-wasting diseases may be normal this year but abnormal in the future. Still, I think it useful for you to understand why your veterinarian may be asking certain questions and ordering the following tests when dealing with your dogs.

HISTORY: The history includes the "signalment" or "age, breed, sex" of the dog. Many of the dogs have not shown any clinical signs of illness until the middle-age years. Most of 35 afflicted SCWT dogs were around 5-6 years of age (range 2-11 years). As far as sex, among 21 PLE dogs, 12 were intact females, 6 were spayed females, and only 3 were males (intact). Among 21 PLN dogs, 8 were intact females, 5 were spayed females, and 8 were males (intact). It appears that females are more at risk. Interestingly, many owners gave the history that their bitch started to show signs of illness soon after a heat or pregnancy. It is unknown whether spaying a female dog will decrease her risk of becoming ill or better her prognosis once she is ill.

Your veterinarian will ask questions about your observations of the dog in the past: When was her last heat? Has there been any weight loss? How is her appetite? What do you feed her? Is there any vomiting or diarrhea? Is she drinking or urinating more than usual? Does she have allergies? Has she been given medications? What states/countries has she been to (certain infectious diseases are more common in certain geographic areas)? When was she vaccinated? When was she last normal? What signs are you seeing? Do you know about any problems concerning her relatives?

PHYSICAL EXAMINATION: During the complete physical examination, your veterinarian may look for hints of abnormal fluid accumulation (edema, ascites, pleural effusion) which may occur secondary to decreased protein concentration in the blood.

DIAGNOSTIC TESTS: My database to screen for evidence of of protein-wasting diseases includes CBC, Chemscreen, Urinalysis, and Urine protein/creatinine ratio. Comrnonly seen abnormalities in the CBC include low numbers of lymphocytes and elevated numbers of eosinophils. Commonly seen abnormalities in the Chemscreen include decreased total protein, decreased serum albumin (also decreased serum globulin in PLE), decreased serum cholesterol in PLE and increased serum cholesterol in PLN. The renal parameters (BUN, creatinine, phosphorus) may not be elevated unless renal failure accompanies PLN. Urine specific gravity (SG) may be dilute or concentrated since the renal failure associated with PLN affects the glomeruli more than the tubules of the kidney tissue and the dog may still be able to concentrate its urine. The urine proteinlcreatinine ratio is a more accurate method of quantitating the protein loss in the urine than the dipstick method. The ratio test is done on the dog's urine, not blood; normally the ratio is less than 1. A full urinalysis with sediment examination helps to clarify whether protein in the urine is due to urinary tract infection (not PLN) or not. If there is a suspicion for PLE, intestinal biopsy may be warranted. We have seen Iymphocytic-plasmacytic enteritis, Iymphangiectasia, granulomatous Iymphangitis, and eosino-philic enteritis. No organisms have been identified; immune-mediated mechanisms are suspected. If PLN is suspected, abdominal ultrasound and kidney biopsy may be indicated. Membrano-proliferative glomerulonephritis and glomerulosclerosis are seen. Immune-mediated disease is suspected. Often we search for some antigen which may cause glomerulonephritis. Blood tests to screen for antibodies to heartworm, Lyme, Ehrlichia, or Babesia may be done but are usually negative. Also, tests for immune-mediated disease such as systemic lupus eTythematosus may be done (ANA, Coombs').

At present, most dogs have done poorly with protein-losing diseases. Some dogs have both PLE and PLN. Dogs with PLE and PLN are hypercoagulable and some have died due to thromboembolism, especially pulmonary. Immunosuppressive steroids may also cause a hyper-coagulable state. Sometimes there appears to be a remission, spontaneously or with therapy. But many dogs don't respond to hypoallergenic diets, immunosuppressive drugs, etc. Hopefully we will be able to prevent the disease in the future, not just deal with treatment once the disease has struck.

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