JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1902445): A nine-year-old Basenji dog
HISTORY: This dog developed polyuria/polydipsia and two months later had 4+ glucosuria, normoglycemia and hypothyroidism (T4 =1.6). Two months later the dog presented in renal failure.
HISTOPATHOLOGIC DESCRIPTION: Kidney (2 sections): Diffusely, the cortical and medullary interstitium is expanded by moderate amounts of fibrous connective tissue that surrounds, separates, and often replaces tubules and glomeruli and is admixed with moderate numbers of lymphocytes, plasma cells, and fewer macrophages that occasionally contain hemosiderin pigment. Multifocally, tubules are atrophied, degenerate, necrotic, or lost. Remaining tubules are often mildly ectatic and are either lined by attenuated epithelium with occasional luminal proteinosis or by epithelial cells with large, up to 15 um diameter, nuclei (karyomegalic cells), with finely stippled chromatin and abundant granular cytoplasm. Within the medulla, tubular epithelium in multifocal to focally extensive areas, has shrunken pyknotic, karryorhectic nuclei and hypereosinophilic cytoplasm (necrosis) and cells are sloughed into tubule lumina; there is dilation or expansion of tubule lumina by granular eosinophilic debris or homogenous proteinacoues fluid (renal papillary necrosis). Multifocally, there is global glomerulosclerosis, periglomerular fibrosis, and mild congestion.
MORPHOLOGIC DIAGNOSIS: Kidney: Fibrosis, interstitial, diffuse, moderate, with tubular degeneration and atrophy, multifocal lymphoplasmacytic nephritis, tubular epithelial cell karyomegaly, and papillary necrosis, Basenji, canine.
ETIOLOGIC DIAGNOSIS: Hereditary tubular nephropathy
CONDITION: Fanconi-like Syndrome
- Fanconi-like Syndrome: An adult onset, slowly progressive, proximal renal tubular dysfunction, resulting in impaired renal tubular reabsorption of amino acids, glucose, and electrolytes; similar to Fanconi syndrome in humans
- Hereditary in the Basenji (recessive lethal gene); also described in Norwegian Elkhounds, Schnauzers, and Shetland Sheepdogs
- It can be produced experimentally in dogs and rats with maleic acid
- An acquired Fanconi syndrome has been reported in dogs secondary to gentamicin toxicity, primary hypoparathyroidism, copper storage hepatopathy, and ethylene glycol toxicity
- Increased membrane cholesterol content in proximal tubule epithelial cells alters the conformational motility and function of membrane transport proteins > impaired renal tubule reabsorption > loss of glucose, phosphate, sodium, potassium, uric acid, and amino acids > progressive renal insufficiency; dehydration and acidosis > fibrosis; renal papillary necrosis > death due to renal failure
TYPICAL CLINICAL FINDINGS:
- Polyuria (results from the glucosuria and natriuresis), polydipsia, hyposthenuria
- Dehydration and acidosis (causes renal papillary necrosis)
- Paradoxic glucosuria (glucosuria with normoglycemia), hyperphosphaturia, proteinuria
- Aminoaciduria (generalized or limited to cystinuria)
- Renal tubular acidosis (proximal tubular, type II) due to failure to resorb filtered bicarbonate
TYPICAL GROSS FINDINGS:
- Often unremarkable; possibly fibrosis and papillary necrosis
NOAH’S ARKIVE: (Canine): F09075
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Initially minimal with irregularly sized tubular epithelial cells (marked hypertrophy & karyomegaly) in the convoluted tubules and loops of Henle
- Nonspecific interstitial fibrosis and tubular atrophy
- Primary tubular transport defects in domestic animals:
- Hyperuricosuria in Dalmatian dogs
- Primary renal glucosuria in Norwegian Elkhounds, Scottish Terriers
- Secondary causes of tubular dysfunction: Diabetes mellitus, acute enterotoxemia, and heavy metal toxicity
- Papillary necrosis may be due to urinary obstruction, pyelonephritis, or nonsteroidal anti-inflammatory drugs
- Humans: Acquired Fanconi Syndrome has been observed with amyloidosis, multiple myeloma, and administration of some drugs
- Fanconi-like syndrome has been reported in Labrador Retrievers, Border Terriers, and a bull
- Karyomegaly of the tubular epithelium may occur secondary to Pyrrolizidine alkaloid toxicity
- Most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi’s syndrome)
Other breed-related diseases of Basenjis:
- Familial hemolytic anemia due to pyruvate kinase deficiency
- Chronic hypertrophic gastritis
- Immunoproliferative enteritis with high circulating levels of IgA
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- Greco DS. Congenital and inherited renal disease of small animals. Vet Clinics of North Amer 2001;31(2):393-399.
- Hsu B, Wehrli S, Yandrasitz J, Fenstermacher E, Palmieri M, Rea C, McNamara P, Bovee K, Segal S. Renal brush border membrane lipid composition in Basenji dogs with spontaneous idiopathic Fanconi Syndrome. Metabolism 1994;43:1073-1078.
- Settles E, Schmidt D. Fanconi syndrome in a Labrador retriever. J Vet Intern Med 1994;8:390-393.