Characterisation and evaluation of predisposing factors for the development of xanthinuria in dogs with leishmaniosis under allopurinol therapy.

Background: Allopurinol, one of the drugs routinely used to treat canine leishmaniosis (CanL), is an inhibitor of the enzyme xanthine oxidase, which plays a fundamental role in purine metabolism. Its inhibitory action on this enzyme leads to a state of hyperxanthinuria, favouring the development of xanthine crystals and/or uroliths. However, not all dogs with CanL treated with allopurinol develop xanthinuria and/or xanthine uroliths, and there is not much information on the possible risk factors that contribute to this event. This study aims to evaluate potential predisposing factors associated with the development of xanthinuria in dogs with a previous diagnosis of CanL that were treated with allopurinol.

Methods: A multicentric, retrospective, observational study was conducted and included dogs with CanL undergoing allopurinol therapy. Dogs that developed xanthinuria (Xgroup) and those without xanthinuria (NXgroup) were selected from cases admitted to three referral hospitals between 2011 and 2022. Medical records were reviewed, and clinical and laboratorial variables were compared between groups. Descriptive statistics, contingency tables and non-parametric tests were used (P < 0.05).

Results: In total, 90 dogs were selected, 45 for each group. Only age and serum alpha-1 globulin concentration were significantly different between groups at day 0. Dogs from Xgroup were younger (median 4 years; interquartile range (IQR) 2-7) than those from NXgroup (median 6 years; IQR 4-9; P = 0.002). At the time of CanL diagnosis, a higher percentage of dogs from NXgroup had decreased serum alpha-1 globulin concentrations (38.9% versus 13.3% in Xgroup, respectively; P = 0.020). In Xgroup, the median time to xanthinuria development after starting allopurinol was 150 days (IQR 31-455).

Conclusions: These results suggest that closer monitoring of young dogs (< 4 years) and those with normal alpha-1 globulin levels at diagnosis is recommended to ascertain the possible development of xanthinuria at an early stage, allowing for early application of measures to reduce the likelihood of its development.