Acquired Proximal Renal Tubular Dysfunction in 9 Labrador Retrievers with Copper‐Associated Hepatitis (2006–2012)

Abstract

Background Copper‐associated hepatitis (CAH) has been well described in Labrador Retrievers. However, the association of CAH with proximal renal tubular dysfunction in this breed has not been characterized. Objectives To report clinical features, hepatic and renal histopathologic findings, tissue copper concentrations, and outcome of Labradors with CAH and proximal renal tubular disease. Animals Nine Labrador Retrievers with renal glucosuria and biopsy‐confirmed CAH. Methods Clinical, clinicopathologic, and light microscopic findings were retrospectively reviewed. Rhodanine staining or atomic emission spectroscopy was performed on all hepatic samples and available renal tissue (4 dogs) to assess copper concentrations. Results Eight dogs had a history of polyuria and polydipsia, and all dogs had increased serum bilirubin concentrations. Five dogs had hyperchloremic metabolic acidosis. Three dogs with acidemia had paradoxical alkalinuria. All renal specimens had increased copper concentrations. Renal tubular vacuolization, degeneration, and regeneration were observed on light microscopy. Four dogs died within 10 days of diagnosis. One dog survived 2 months; 4 dogs survived more than 1 year. In long‐term survivors, including 2 that did not undergo immediate copper chelation, resolution of renal tubular dysfunction occurred within weeks to months. Conclusions and Clinical Importance Labrador Retrievers with CAH can develop clinical and laboratory evidence of renal tubular dysfunction in association with increased renal copper concentrations. Given the rarity of renal tubular disorders, detection of renal glucosuria and increased ALT activity in a Labrador Retriever is suggestive of CAH. Although renal tubular dysfunction may indicate advanced disease, successful long‐term outcome is possible with a variety of therapies.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…Rarely individuals with high concentrations of hepatic Cu can undergo an acute necroinflammatory crisis releasing Cu and causing a Coombs' negative hemolytic anemia . Additionally, an acquired Fanconi‐like syndrome characterized by euglycemic glucosuria associated with renal Cu accumulation also can occur in some cases …”

“…Details and evidence for breed, sex, and age predispositions are summarized in Supporting Information Table S1. There is strong evidence in ≥2 studies for an increased prevalence of CH in BT, Doberman Pinschers, LR, Dalmatians, American and English Cocker Spaniels, English Springer Spaniels, and West Highland White Terriers in several countries. In addition, in Sweden the Scottish Terrier, and in the United Kingdom the Cairn Terrier, Great Dane, Samoyed, Yorkshire Terrier, and Jack Russell Terrier are predisposed .…”

Fanconi syndrome in dog in the UK

“…This syndrome can be inherited, as documented in the basenji breed, due to a FAN1 mutation (Farias and others 2012), and it has also been reported in labrador retrievers with copper-associated hepatopathy (Langlois and others 2013). Furthermore, acquired Fanconi syndrome has been associated with exposure to heavy metals, antibiotics, leptospirosis and jerky treats.…”

Ammonium tetrathiomolybdate treatment of copper‐associated hepatopathy in dogs

“…The disease has garnered considerable attention from the veterinary community in recent years . Once thought to be a rare condition affecting only Bedlington Terriers, CAH is widely recognized in Labrador Retrievers, Doberman Pinschers, West Highland White Terriers, and Dalmatians . More recently, CAH has been recognized in various breeds and crosses not typically considered predisposed to CAH .…”