Biologic Features. Hereditary nephritis has been reported in Samoyed dogs.' Renal disease in ... supported by Public Health Service Grant RR-00301 from.
ANIMAL MODEL OF HUMAN DISEASE
Hereditary Nephritis in Samoyed
From the Department of Pathology, Ontario Veterinary College, Guelph, Ontario, Canada, and the Department of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada
BARBARA JANSEN, DVM, PAUL S. THORNER, MD, AMREEK SINGH, PhD, JIM M. PATrERSON, DVM, JOHN H. LUMSDEN, DVM, VICTOR E. VALLI, DVM, PhD, REUBEN BAUMAL, MD, PhD, and PARVATHI K. BASRUR, PhD
Biologic Features Hereditary nephritis has been reported in Samoyed dogs.' Renal disease in these animals is first detected at approximately 4 months of age with the onset of proteinuria, microscopic hematuria, and hypoalbuminemia. Elevations in serum BUN and creatinine are first seen at 6 months, and further biochemical features of renal failure become established at 9 months. Death ensues by 12-16 months of age. Unaffected dogs show a normal urinalysis and maintain normal serum biochemical profiles. The disease appears to have an X-linked recessive genetic basis, because it affects male dogs and is inherited through female carriers. Serial renal biopsies demonstrate progressive changes. Lesions are noted by electron microscopy as early as 1 month of age, when light microscopy is still normal. Glomerular capillary basement membranes (GCBMs) show regions of subepithelial and subendothelial lucency and reduplication or splitting of the lamina densa into multiple layers, with small, round, electron-dense particles between the layers (Figure 1). No electron-dense immune complexes are seen. These changes involve discrete portions of GCBM, and many capillary loops have a normal appearance. The lesion becomes more severe with time, as indicated by increased thickening and splitting of GCBMs and more widespread involvement of capillary loops. Eventually all glomerular capillaries are affected. In addition, podocytes have focal fusion of foot processes and microvillus transformation. Endothelial and mesangial cells appear normal by electron microscopy, but paramesangial regions have mild increases in matrix, with occasional particulate de-
bris. Glomerulosclerosis becomes complete by 8-10 months of age. Tubules and interstitial blood vessels appear normal, and their basement membranes do not show the changes seen in the glomerular capillaries. These ultrastructural changes are paralleled by segmental GCBM splitting, which is first seen with use of the periodic acid-Schiff stain when the animal is 4.5 months old. This splitting becomes global by 810 months. Some glomeruli show segmental sclerotic lesions with capsular adhesions and parietal cell proliferation. Glomerulosclerosis is well established by 8-10 months.
Comparison With Human Disease Human hereditary nephritis usually begins in childhood with hematuria (microscopic or gross) and/or proteinuria. Eventually a nephrotic syndrome may develop. Males often progress to renal failure by the third decade, whereas females usually have a milder disease and may not progress to renal failure. Various clinical conditions may be associated with hereditary nephritis in man, including progressive sensorineural hearing loss, lesions involving the lens (spherophakia, cataracts, anterior lenticonus) or retina (retinitis pigPublication sponsored by the Registry of Comparative Pathology of the Armed Forces Institute of Pathology and supported by Public Health Service Grant RR-00301 from the Division of Research Resources, National Institutes of Health, under the auspices of Universities Associated for Research and Education in Pathology, Inc. Address reprint requests to Dr. R. Baumal, Department of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.