Diagnosis of canine urinary tract infections (UTI) is based on a positive urine culture and inflammatory sediment. In practice, culture and/or sediment analysis are not always performed prior to using antibiotics; which is at odds with rational prescribing. In-clinic measurement of biomarkers to specifically test for a UTI, would therefore be of great value. In humans, the concentration of a number of urinary biomarkers increases in UTI. As yet, these have not been evaluated in dogs to determine if they behave similarly.

Aim: to determine whether measuring inflammatory biomarkers in canine urine could correctly identify bacterial infection.

Hypothesis: CRP, IL-6, procalcitonin and lactoferrin concentrations in canine urine with confirmed infections are significantly increased compared with controls.

Specific canine ELISAs were developed for CRP, IL-6, procalcitonin and lactoferrin. These were selected given their association with UTI in human medicine. Assays underwent comprehensive validation prior to initiating this study.

The above biomarkers were measured in residual urine samples following routine urinalysis, from a cohort of dogs with confirmed UTI (n=25) and from a control cohort without UTI (n=26). Inclusion criteria for the UTI group was a positive urine culture and inflammatory urine sediment. Control samples had an inactive sediment and sterile culture. This study was approved by the establishment's ethical review committee.

For comparing non-parametric datasets, Mann-Whitney tests were performed; for multiple comparisons between non-parametric datasets, the Kruskall Wallis test was used.

There was a significant increase in CRP (p<0.009) and lactoferrin (p<0.018) concentrations between UTI samples and controls. Enterococci significantly increased CRP concentrations compared with Coliforms (p<0.008) and mixed bacterial populations (p<0.03). Enterococci significantly increased IL-6 concentrations compared with Coliforms (p<0.03). Enterococci significantly increased procalcitonin concentrations compared with mixed bacterial populations (p<0.0004). ROC curves were used to determine sensitivity and specificity for CRP and lactoferrin for detecting a UTI. A CRP cut-off of 1.87ng/ml, gave a sensitivity of 52% and specificity of 90%. A lactoferrin cut-off of 151.3ng/ml, gave a sensitivity of 80% and specificity of 100%. Combining CRP and lactoferrin gave a sensitivity and specificity of 100% for a UTI. Correlation between CRP and lactoferrin was excellent (r=0.95).

This pilot study demonstrates novel urine biomarkers, either alone or in combination, can identify UTI in dogs. Some bacteria increase the concentration of biomarkers in the urine more than others. These results demonstrate potential value in measuring urinary biomarkers in-clinic to screen urine samples for infection, improving antibiotic stewardship.

Disclosures

Disclosures to report:

Dr Dunning has a consultancy role for AVACTA animal health. Dr Slater is Chief Scientific Officer for AVACTA animal health Dr's Moody and Barrass-Hemmens are assay development scientists employed by AVACTA animal health.