CASE REPORT

Familial Glomerulonephritis inDoberman Pinscher Dogs

B.P WILCOCK ANDJ.M. PATTERSON*

SummaryProgressive renal disease in 13 related

Doberman pinscher dogs had the histologicalcriteria of membranoproliferative glomeru-lonephritis. Polyuria, polydipsia and weightloss were the usual initial abnormalities andwere observed at one year of age or less inseven of I 1 dogs diagnosed antemortem ashaving renal disease. There was no sexpredilection. All dogs were traced to acommon male dog no more than fourgenerations previously.

Resume~Glomerulo-nephrite familiale, chez des chiensDobermanUne maladie renale progressive, qui affec-

tait 13 chiens Doberman apparentes, presen-tait les crit&res histologiques d'une glomerulo-nephrite membraneuse. Les signes cliniquesinitiaux usuels se caracterisaient par de lapolyurie, de la polydipsie et une perte de poids;ils se manifesterent vers l'age d'un an, oumeme plus t6t, chez sept des 11 su.jets chezlesquels on avait diagnostique, de leur vivant,une maladie renale. Cette condition affectaitindifferemment des males et des femelles.Tous ces chiens appartenaient (i la quatriemegeneration d'un meme geniteur.

IntroductionBreed predisposition to renal disease in

dogs has been documented for cocker spaniels(7), Norwegian elkhounds (2) and Samoyeds(1). The disease in spaniels was originallytermed renal cortical hypoplasia, but usingcurrent criteria of classification the lesion was

that of nonspecific end-stage kidney (2). Thedisease in elkhounds and Samoyeds wassimilar, with variable age at clinical onset andgeneralized glomerular and interstitial diseaseat necropsy. In elkhounds the earliest changewas periglomerular fibrosis followed by in-terstitial fibrosis, proliferative glomerularchanges and interstitial mononuclear leu-cocyte accumulation. An immunologicalbasis for the glomerular lesion was notdemonstrated (2). In Samoyeds the advancedrenal lesion in each case precluded a morespecific diagnosis other than chronic gen-eralized renal disease. Glomerular prolifera-tive and sclerotic changes were more promi-nent than in the elkhound disease and the ageof onset of clinical renal failure was younger(nine to 11 mo) than in elkhounds (up to fouryrs). Medullary and cortical interstitialfibrosis, vascular lesions and interstitial in-flammation were considered nonspecificchanges in both diseases.

Breed or line predisposition to renal diseaseof young dogs has been proposed for Germanshepherds, dachshunds, Lhasa apsos, ShihTzus and miniature schnauzers (10), but datato support this impression have not beenpublished. This report describes generalizedrenal disease in 13 related Dobermanpinschers from the Toronto area.

Clinical DataBetween February 1976 and July 1978, 11

Doberman pinschers were admitted to theSmall Animal Clinic, Ontario VeterinaryCollege with histories suggestive of acute orchronic renal disease. Five were males, sixwere females and most had long histories ofpolyuria, polydipsia, nocturia and weightloss. In seven of the dogs the age at onset ofclinical signs was less than one year. Thesignificant features of each medical historyare presented in Table I. In most casessubsequent clinical and laboratory findingssupported the diagnosis of severe glomerulardisease (Table II).

Features common to all dogs with renalfailure were marked proteinuria, mild non-regenerative anemia, and elevated serumconcentrations of urea nitrogen, creatinineand, when measured, cholesterol. Most caseshad received intensive antibiotic and steroidtherapy, but renal function continued to

Can. vet. J. 20: 244-249 (September 1979)

*Department of Pathology (Wilcock) and Department of Clinical Studies (Patterson). Ontario Veterinary College.Universitv of Guelph. Guelph. Ontario NIG 2WI.

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TABLE ICLINICAL HISTORIES OF DOBERMAN PINSCHERS WITH GLOMERULONEPHRITIS

Age at Onset of Age atDog Sex Clinical Signs Initial Signs Euthanasia

I F 6 wk PU/PD,a poor growth 6 mo2 F I yr PU,lPD 18 mo3 F I yr PU/PD, poor growth 18 mo4 M 10 mo PU/PD, ascites; edema 14 mo5 F 6 mo PU/PD, nocturia 3 yr6 F 6wk PU/PD 9 yr7 M Iyr PU / PD 5 yr8 F 2, 5 yr Vomiting 2, 5 yr9 M 4, 5 yr Wt. loss, bleeding 4, 5 yr10 M 8 yr PU/PD, weight loss11 F No signs of renal disease 4 yr12 M No signs of renal disease13 M 2, 5yr PU/PD 4 yr

aPolyuria, polydipsia

deteriorate. Two dogs (No. 8, 10) had no animals. Both kidneys were firm and slightlybiochemical alterations suggesting advanced smaller than normal. The surface was finelyrenal disease but did have persistent pro- and diffusely pitted. The cortex was lightteinuria and, in one dog, neutrophils in the brown and often had numerous small (1-2urinary sediment. One dog (No. 9) died from mm) spherical cysts. There were miliary smallliver failure associated with portosystemic white dots in a pattern suggesting abnormally-venous shunts. Glomerular disease was found conspicuous glomeruli. The capsule wasat necropsy although antemortem routine easily removed. Medulla was either normal orurinalysis and blood chemistry had detected it was pale and rubbery. In three bitches theno renal dysfunction. Tissues from two other right ureter and kidney were absent. One ofDoberman pinschers which died with renal these bitches also had agenesis of right uterinedisease were submitted to the Veterinary horn. Only one of the three had compensatoryServices Laboratory, Guelph for histological hypertrophy of the remaining kidney (87 g).examination. Changes in other organs were those asso-

ciated with advanced renal disease (3, 5) andPathologj will not be further described (Table III).

Significant gross extrarenal lesions in each Microscopic renal lesions were consistentlyof 10 dogs necropsied are listed in Table III. found in glomeruli. Specimens with severeIn every dog the most significant lesion was in glomerular changes also had tubular andthe kidneys and varied little among the 10 interstitial disease. The mildest glomerular

TABLE IILABORATORY FINDINGS IN DOBERMAN PINSCHER DOGS WITH GLOMERULONEPHRITIS

Serum Serum Urinary UrineBUN Creatinine Phosphorous Cholesterol Protein Specific

Dog (mg/dl) (mg/dl) (mg/dl) (mg/dl) (mg/dl) GravityNumber Initial Final Initial Final Initial Final Initial Final Initial Final Initial Final

1 94 3,3 6,4 337 75 1,0132 35 125 ND ND ND ND ND3 140 117 7,8 6,0 273 +++ 1,0174 35 125 7,1 6,5 18 526 500 800 1,039 1,0165 30 40 ND ND 267 100 150 1,023 1,0186 128 6,2 9,7 ND 75 1,0127 73 220 10,8 10 22 ND 375 200 1,018 1,0108 294 290 13 22 ND 500 200 1,014 1,0139 285 9 23 ND 500 1,01610 11 ND 4,2 ND 500 1,004 1,02311 7 ND ND ND 0 1,02312 13 ND ND ND 600 750 1,058 1,02013 100 23 ND ND +++a 1,020aCorresponds to about 300 mg/dl

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TABLE IIIEXTRAREN'Ai GROSS LESIONS IN DOBERMAN PINSCHERS WIlH RENAL DISEASE

Stunting Gatstric Right RenalDog Emaciation Oral Ulcers Gastric Ulcers Mineralization Hyperparathvroidism Aplasia

+

2 + NR NR NR +3 + +

4 + - _5 + -6 + - + + +

7 + + +

8 + - + - + +

9 + + + +

I bb

12' - - NR NR NR13a + NR NR NR NR

aSelected tissues received for histological examination. NR = not reported.bEuthanized because of hepatic encephalopathy. Cirrhosis was found at necropsy.cDog died with lymphosarcoma two years after discharge from O.V.C. Findings listed are from O.V.C. data.

lesion was in dogs 5 and I 1, consisting of focal lar lesions in the same kidney. Commonsegmental mesangial thickening and accen- findings were mesangial cell proliferation,tuation of glomerular lobulation. Hyaline increased mesangial matrix and glomerularthickening of the mesangium was most sclerosis. Mesangial cell proliferation wasobvious adjacent to the afferent arteriole either segmental or diffuse and severely(Figure 1). affected glomeruli often had adhesions be-

In dogs killed in advanced renal disease, it tween peripheral capillary loops and hyper-was usual to see a wide spectrum of glomeru- trophic parietal epithelium (Figure 2).

7*' AHG;'} Z i - i' /t FR 2. Glomerular tuft adhesions and intratubularFIGURE 1. Increased mesangial prominence in a glome- protein casts in the kidney from a four year oldrulus ot a six month old Doberman pinscher bitch with Doberman pinscher. There is slight interstitial fibrosispoor growth and persistent polyuria. Three micrometers. and patchy flattening of tubular epithelium. ThreePAS. X116. micrometers. PAS. X40.

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FIGURE 3. Shrunken glomerular tufts in fluid-filled.dilated Bowman's spaces. Interstitial and tubularchanges are scant. Three micrometers. H & E. X24.

Glomerular sclerosis was seen as shrunkenglomerular tufts at the vascular pole of cysticBowman's spaces which corresponded to thecortical cysts seen grossly (Figure 3). Par-ticularly in areas of interstitial fibrosis theglomeruli were sclerotic and tightly sur-rounded by a thick fibrous capsule (Figure4).

Tubular and interstitial lesions paralleledglomerular changes. Kidneys with mildglomerular disease had no tubular or inter-stitial lesions. In kidneys with severe glome-rulonephritis the distribution of tubular loss,fibrosis and mononuclear leucocyte infiltra-tion corresponded to the distribution ofnephrons served by severely altered glomeruli(Figure 5). There was compensatory hyper-trophy and hyperplasia of tubules associatedwith mildly affected glomeruli in otherwiseseverely affected kidneys. In the medulla therewas usually fibrosis with tubular loss andoccasional accumulations of mononuclearleucocytes. The histological diagnosis wasmembranoproliferative glomerulonephritis.

FIGURE Glomerularsclerosis .interstitialfibrosis andtubular loss in a Doberman pinscher with advanced renal

disease. Three micrometers. H & E. X96.

Pedigree Ana/isisPedigrees were obtained from nine affected

dogs. All were related and could be traced,usually through both sire and dam, to acommon male (dog A) no more than fourgenerations previously. His son, dog B,appeared in all pedigrees except that ofdog C,a litter brother (Figure 6).

DiscussionThe diagnosis of membranoproliferative

(mesangiocapillary) glomerulonephritis wasbased upon the observation of bilateral,generalized and predominantly glomerulardisease characterized by segmental or diffusemesangial thickening and lobular accentua-tion (4, 6). Exudative lesions were absent andcapillary thickening was seen only in kidneyswith advanced disease. In three cases extra-glomerular renal lesions were minor or

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-8F IKK' w s a

FIGURF 5. Alternating bands of scarring and tubularhyperplasia in a severely affected kidney. Three micro-meters. H & E. X24.

absent. Glomerular changes were invariablymore severe than the interstitial and tubularlesions. The preponderance ofyoung animals,slow but inexorable clinical course andresistance to corticosteroid therapy are simi-lar to membranoproliferative glomerulone-phritis in man (4, 6). Lesions meeting thepathological criteria of membranoprolifera-tive glomerulonephritis are reported to becommon in dogs with glomerular disease butno familial predisposition has hitherto beenreported (8, 11, 14). Familial renal disease incocker spaniels and in Samoyeds may beglomerulonephritis but advanced lesions inthe kidneys examined in these studies pre-clude interpretation as to the initial classifica-tion of the renal disease. In Norwegian elk-hounds the early lesions are clearly differentfrom those described in this paper in thatperiglomerular fibrosis and hyperplasia ofparietal epithelial cells are the prominentearly changes (2). In interesting parallel to

C'

A-e B' 0

p Fl F2 F3 F4

FIGURE 6. Schematic representation of familial patternof glomerulonephritis in Doberman pinschers. Dogs Aand B (both dead) were of unknown renal status. Dogsencircled are descended from B through both dam andsire, others through sire only. Each line representsseparate litter.

the findings in Doberman pinschers, mem-branoproliferative glomerulonephritis (13)and renal agenesis (9, 12, 14) have beenreported in beagle dogs raised in pharmaceu-tical research colonies in Canada and in theUnited States. Glomerulonephritis and renalagenesis were not reported in the same dog.The frequency of this form of renal disease

among Doberman pinschers is unknown, butthe affected line of dogs is very prominentamong show dogs and, presumably, amongthe pet population of Doberman pinschers aswell. The strong familial association evidentin our pedigree data suggests that siblings andoffspring of affected dogs have a high risk ofrenal disease. Until the breeders of the knownaffected dogs are prepared to disclose com-plete breeding information for the purpose ofmedical follow-up of related dogs, the fre-quency and mode of transmission will remainunknown. For the individual affected dog theclinical course is usually prolonged butrefractory to drug therapy and eventuallyfatal.

References1. BERNARD. M.A. and V.E. VALLI. Familial renal disease

in Samoyed dogs. Can. vet. J. 18: 18 1-189. 1977.2. FINCO. D.R.. J.R. DUNCAN. W.A. CROWELL and M.L.

HULSEY. Familial renal disease in Norwegian elk-hound dogs: morphologic examinations. Am. J. vet.Res. 38: 941-947. 1977.

3. FINCO. D.R.. C.A. OSBORNE and D.G. LOW. Physiologyand pathophysiology of renal failure. In Textbook ofVeterinary Internal Medicine. S.J. Ettinger. Ed.pp. 1453-1464. Philadelphia: W.B. Saunders Com-pany. 1975.

4. HEPTINSTALL. R.H. Pathology of the Kidney. Vol. 1.pp. 412-425. Boston: Little, Brown and Co. 1974.

5. JUBB. K.V.F. and P.C. KENNEDY. Pathology of domesticAnimals, Vol. 2. pp. 329-332. New York: AcademicPress. 1970.

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6. KASHGARIAN. M.. J.P. HAYSLETT and B.H. SPARGO.

Renal disease. Am. J. Path. 89: 187-272. 1977.7. KROOK. L. The pathology of renal cortical hypo-

plasia in the dog. Nord. VetMed. 9: 161-176. 1957.8. MURRAY. M. and N.G. WRIGHT. A morphologic study

of canine glomerulonephritis. Lab. Invest. 30:213-221. 1974.

9. MURTI. G.S. Agenesis and dysgenesis of caninekidneys. J. Am. vet. med. Ass. 146: 1120-1124. 1965.

10. OSBORNE. C.A.. D.G. LOW and D.R. FINCO. Canine andFeline Urology. pp. 162-163. Philadelphia: W.B.Saunders. 1972.

I1. OSBORNE. C.A. and R.L. VERNIER. Glomerulonephritis

in the dog and cat: a comparative review. J. Am.anim. hosp. Ass. 9: 101-127. 1973.

12. ROBBINS. G.R. Unilateral renal agenesis in the beagle.Vet. Rec. 77: 1345-1347. 1965.

13. STUART. B.P.. R.D. PHEMISTER and R.W. THOMASSEN.

Glomerular lesions associated with proteinuria inclinically healthy dogs. Vet. Path. 12: 125-144. 1975.

14. VYMETAL. F. Renal aplasia in beagles. Vet. Rec. 77:1344-1345. 1965.

15. WRIGHT. N.G:. E.W. FISHER. W.I. MORRISON. W.B. THOM-

SON and A.S. NASH. Chronic renal failure in dogs: acomparative clinical and morphological study ofchronic glomerulonephritis and chronic interstitialnephritis. Vet. Rec. 98: 288-293. 1976.

LETTER TO THE EDITOR

"For not Looking than not Knowing"

DEAR SIR:

Most practitioners have been aware of theabove phrase either from training at veterin-ary colleges or from seminars, etc. . .

A four year old German shepherd malecross was presented after being hit by a cartwelve hours previously. The dog favouredthe left hind leg and ambulated on three legs.A pain killer,' had been administered theprevious night by a pharmacist. The ownerhad noted that the dog would occasionallyhyperventilate when given tranquilizers priorto presentation but had showed no adversedrug reactions.On examination, several superficial lacera-

tions were present on the medial left thigh,colour of mucosa and capillary refill werenormal, and the animal appeared bright andalert. Auscultation revealed slight muffledheart sounds on the right thorax, but ab-dominal palpation revealed no abnormalities.Twelve milligrams of xylazine2 were ad-ministered intravenously and lateral andventral/dorsal radiographs of the pelvis weretaken. The diagnosis was established as adislocated left hip, and the animal was given125 mg thiopental sodium3 to facilitate man-ipulations of the hip joint. The hip was

reduced and a light flexion bandage applied.The animal appeared to make a smoothrecovery from anesthesia then went intorespiratory distress, and collapsed. Sup-portive treatment had no effect, and theanimal died one hour later.

At necropsy, a 5 cm tear was discovered onthe right lateral muscular portion of thediaphragm, with stomach and approximatelyone metre of small intestine projecting intothe thoracic cavity. On further questioning,the owner mentioned that the animal hadalways shown poor exercise tolerance. It wastheorized that the herniation was eithercongenital or had occurred prior to the caraccident. The combined effects of shock,herniated intestinal contents and barbiturateshad compromised the respiratory system tothe point where cardiovascular collapse wasnonreversible.

This case demonstrates the importance of athorough history taking and physical exam-ination in any victims of automobile acci-dents.

J. GAMMIE, B.Sc.. M.Sc.. D.V.M.

Okanagan Animal Medical Clinic275 Okanagan Avenue EastPenticton, British ColumbiaV2A 3J8

'Talwin, Winthrop Laboratories, Division of Sterling Drug, Aurora, Ontario.2Rompun, Haver-Lockhart Laboratories, Division of Bayvet Corp., Shawnee Mission, Kansas.3Pentothal sodium, Abbott Laboratories Ltd., Montreal, Quebec.

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