HP04 - Relative Exchangeable Copper and Ultrafiltered Urine Copper-to-Creatinine ratio for Diagnosis of Copper-Associated Hepatitis in Dogs

Abstract: Background – Relative exchangeable copper (REC) and urine small copper carrier-to-creatinine ratios (Cu/Cr-ratio) are increased in humans with Wilson’s disease and rodent models. Objective – Determine whether serum REC and 3 kDa ultrafiltered urine Cu/Cr-ratio (small copper carrier surrogate) could serve as potential biomarkers for copper-associated hepatitis (CAH) in dogs. Animals – 16 dogs with CAH, 8 with idiopathic chronic hepatitis (ICH), 18 with congenital portosystemic shunt (CPSS), and 55 healthy controls (HC). Methods – Retrospective cross-sectional study. Exchangeable copper was measured by incubating serum with 5 g/L EDTA, followed by ultracentrifugation. The REC was calculated as the percentage of exchangeable copper relative to the total serum copper. Urine was ultrafiltered using a 3 kDa filter followed by measurement of copper concentrations normalized to creatinine concentrations. For all samples, copper concentrations were measured by ICP-MS. Results – REC was higher in CAH dogs than in HC (P = .03). Ultrafiltered urine Cu/Cr-ratio was higher in dogs with CAH and ICH compared to HC (P <.0001; P = .01) and compared to dogs with CPSS (P = .02; P = .05). There were no other significant differences between groups for either parameter (Table 1). The area under the receiver operating characteristic curve (95% confidence interval) of REC and ultrafiltered urine Cu/Cr-ratio for differentiating between dogs with CAH and ICH were 0.59 (0.32-0.86) and 0.61 (0.35-0.86), respectively. Conclusions and clinical importance – Our results do not support the utility of REC or ultrafiltered urine Cu/Cr-ratio for differentiating dogs with CAH from ICH.