Kenneth C. Bovee, DVM, M Med Sc
Renal dysplasia is defined as the formation of abnormal nephrons with excessive mesenchymal stroma and without inflammation. This hereditary disease is seen in many breeds of dogs but appears most frequently in the Shih Tzu. Other non specific terms have been used in the literature such as juvenile renal disease, familial renal disease and hereditary nephropathy, but in this form of dysplasia there is a rather specific and dominant histologic feature of the persistence of fetal glomeruli.
The severity of this disease is variable depending of the population of normal and abnormal nephrons. In severe cases puppies may fade quickly after birth or live 3-6 months before dying of chronic renal failure. Signs include profound polydypsia, polyuria, failure to grow, anemia, renal osteodystrophy and other typical findings of chronic renal failure. Such findings are peculiar since they occur in immature dogs and the diagnosis may be missed. In moderately affected dogs excessive water intake is always a prominent historical finding with reduced growth rates and azotemia. Most dogs with this moderate form live 1-2 years and gradually fail due to chronic renal failure. A lesser affected group, termed mild dysplasia, may develop renal insufficiency in adulthood or remain clinically normal and live a full life term with only moderate polyuria.
The diagnosis is made by finding evidence of renal failure in immature or young adults. Routine laboratory findings are azotemia, hyperphosphatemia, and non responsive anemia. Urinalysis reveals dilute urine out of proportion to the degree of azotemia, sediment is unremarkable and proteinuria is absent. Radiographs or ultrasound studies will reveal reduced renal size; poor visualization with a intravenous pyelogram, and small fibrous kidneys using ultrasound. A definitive diagnosis requires renal tissue for histologic examination collected at necropsy or renal biopsy. A wedge renal biopsy of the renal cortex is the most accurate method since it provides a large number of glomeruli for examination. A needle biopsy is generally not helpful.
Because the canine kidney is peculiar in that a major portion of development occurs after birth and up to 3 months, interpretation of renal biopsies requires special attention. Biopsies collected before 3 months of age are not diagnostic in many cases. At least 100 glomeruli are required in a biopsy specimen to make an accurate evaluation. The histologic features are immature or fetal glomeruli, persistent mesenchymal tissue, interstitial fibrosis without active inflammation, atypical tubular epithelium and mineralization of tubules in severe cases. The severity of renal dysfunction correlates to the percentage of fetal glomeruli. We have studied hundreds of renal biopsies over 20 years and have arrived at a percentage of fetal glomeruli that will result in clinical renal failure. In general, if the percentage of fetal glomeruli is more that 25% of the total the dog will have a moderately severe or severe form of the disease and proceed to failure. If the percentage is 10-25% of the total, the dog will have renal insufficiency and show signs of real failure in adulthood. Dogs with less than 10% fetal glomeruli will generally remain asymptomatic.
The prevalence of renal dysplasia in this breed is very high in North America. In a study of 74 random dogs evaluated with wedge renal biopsy, only 16% were free of any histologic evidence of the disease. Among the remaining, about 52% had 1-5% fetal glomeruli, while 20% were moderately affected with 6-15% fetal glomeruli. The remaining 12% had more than 15% fetal glomeruli. These findings suggest that the genetic character of the disease is very high and variable in this breed. Because many dogs are mildly affected and escape detection in the absence of renal biopsy, the question arises as to the genetic transmission of the defect in normal appearing dogs.
While renal dysplasia has been reported in 16 breeds of dogs, the Shih Tzu breed is in a category by itself in regard to wide spread prevalence at least in North America. The only other breed that has a high prevalence in our experience is the Lhasa Apso.
CHARACTER OF DYSPLASIA
A number of studies were carried out to further characterize this disease. Over a number of years we have worked with many breeders who are concerned about the apparent high transmission of the disease and the type of renal dysfunction caused by this developmental defect. Renal clearance studies were performed on moderately affected and severely affected dogs to determine if specific tubular or glomerular dysfunctions were present. Classical renal clearance studies included glomerular filtration rate, quantification of proteinuria, tubular reabsorption of electrolytes, glucose, acid-base, and amino acids. Results did not indicate specific glomerular or tubular defects except for the inability to conserve water which appears to be a nephrogenic diabetes insipidus like defect. Proteinuria is not a component of the disease. Renal clearance abnormalities were consistent with those found in any dog with chronic renal failure independent of etiology.
Studies were performed to determine if there was a good agreement between necropsy results and wedge renal biopsy results to arrive at a consistent percent fetal glomeruli reading. Good agreement was found between the 2 methods when biopsy results were compared to subsequent necropsy findings. Another study revealed that both left and right kidneys were similarly affected. Another study addressed the possible progression of histologic changes over 9-24 months using repeat biopsy studies. In most cases a pathologic progression was not seen in the percentage of fetal glomeruli.
PATTERN OF INHERITANCE
The evaluation of many pedigrees indicates the defect is not sex linked. Data from incomplete pedigrees from breeders indicates either an autosomal dominant inheritance with incomplete penetrance or a recessive inheritance.
Since pedigrees from breeders do not contain complete or uniform biopsy data, we undertook a project to evaluate the pattern of transmission based on renal biopsies of all adults and offspring over a period of 10 years in cooperation with a limited breeder group. Adults dogs included in the study had biopsies performed before selective breeding to others with known and a low percentage of fetal glomeruli. Breeding pairs were selected with the lowest percentage of fetal glomeruli or 0 percentage fetal glomeruli. In some cases data from 3-4 generations with repeated breedings were collected. The objective was to determine if this selective breeding would reduce or eliminate the presence of abnormal glomeruli.
Over a 10 year period 52 matings involving 143 dogs were carried out. The majority of breeding adults had 0-5% fetal glomeruli. The results did not fit a classical genetic pattern which is not surprising given the degree of inbreeding in this breed. The mating of dogs with a low percentage fetal glomeruli (1-5%) did not result in offspring with only low fetal glomeruli. Some of these matings produced dogs with severe disease. The offspring of matings from 0% or 1% adults had lower fetal glomeruli but seldom 0% fetal glomeruli. Even the breeding of 0% adults with each other resulted in offspring with 1-3% fetal glomeruli. An outcross breeding of a Shih Tzu with 2% fetal glomeruli with a normal Poodle mix resulted in a litter with all being affected (4-l0% fetal glomeruli).
Results of this breeding study indicate that selective breeding based on renal biopsies can limit the production of severely affected offspring in some cases but this plan failed to eliminate the transmission of fetal glomeruli. The pattern of genetic transmission does not fit any simple pattern. Results are most consistent with an autosomal dominance pattern with incomplete penetrance which is supported by the production of affected pups from an outcross breeding.
The prevalence of this defect is approximately 85% in this breed in North America. The severity of the defect is highly variable. Only a small percentage of those affected have severe disease and 5-10% die of chronic renal failure. Wedge renal biopsy is required to detect affected dogs. Since the majority of affected dogs go undetected and can pass the defect on, control is extremely difficult. Selective breeding using renal biopsy results can control the spread of severely affected cases but it cannot be relied upon to eliminate the defect at least in this study. The mode of inheritance is most consistent with an autosomal dominance pattern with incomplete penetrance.
1. Bovee,KC; Inherited and Metabolic Renal Disease in CANINE NEPHROLOGY. Harwal Pub. 1984
2. Picut,CA and RM Lewis: Microscopic features of canine renal dysplasia. Vet Pathol. 24:l56-l63, l987
3. Hoppe,A,L Swenson,L Jonsson, A Hadhammar: Progressive nephropathy due to renal dysplasia in Shis Tzu dogs in Sweden: Clinical- pathologic and genetic study. J Small An Practice 37: 83-91, l990