Allopurinol-induced xanthinuria: a prospective and retrospective study
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Introduction – Allopurinol is used to treat Canine Leishmaniasis (CanL), a chronic systemic disease caused by the protozoa Leishmania infantum and characterized by exfoliative dermatitis and renal failure. Allopurinol is a parasitistatic drug which is known to interfere with the purine metabolism of the dog, causing xanthinuria as a side effect. Few studies are conducted investigating xanthinuria in dogs with CanL. Aim of this research was to determine the incidence of xanthinuria and find possible correlations with dosage, length of treatment, specific gravity and pH in dogs with CanL. Another aim was to investigate the effect of storage time on xanthinuria. The final aim was to investigate the incidence of xanthine-uroliths. Material and methods – Prospective study: Urine samples of client-owned dogs with CanL receiving allopurinol treatment were collected and limited urinalysis including specific gravity, pH and sediment analysis was performed within 3 hours after sample collection. Urinalysis was repeated after 24h and 48h. Retrospective study: Medical records of 145 dogs with CanL were retrospectively reviewed. Dogs were included if medical records reported at least one complete urinalysis performed during allopurinol treatment. In order to investigate the incidence of xanthine-uroliths, all included dogs were screened on reports of abdominal ultrasounds performed during allopurinol treatment. Results – Prospective study: A total of 10 dogs were included in this study. Six out of 10 dogs (60%) presented with xanthinuria. Minimum dosage of allopurinol and minimum length of treatment resulting in xanthinuria was 16,2 mg/kg/day and 68 days, respectively. There was a correlation found between dosage and incidence of xanthinuria (p=0,015). Strong correlations were found for both specific gravity and pH between day 1, 2 and 3 (p=<0,001 for all). Amount of xanthine was significantly different between day 1 – day 2 (p=0,047) and day 1 – day 3 (p=0,031). Retrospective study: A total of 57 dogs were included in this study. Thirty-three out of 57 dogs (58%) presented with xanthinuria during at least one urinalysis. Minimum dosage of allopurinol and length of treatment resulting in xanthinuria was 15 mg/kg/day and 13 days, respectively. Xanthinuria was present in 59/155 urinalyses (38%) performed during allopurinol treatment. A strong correlation was found between specific gravity and incidence of xanthinuria (p<0,001). Fifteen out of 57 dogs (26%) had reports of abdominal ultrasounds during allopurinol treatment. Xanthine-uroliths were reported in 12/15 dogs (80%) with ultrasound reports and clinical signs developed in 5/12 dogs (43%) with xanthine-uroliths. Conclusions – An incidence of xanthinuria of 58-60% was found in this research, although an incidence of 45-55% is presumably more accurate. Because of the strong correlation between specific gravity and incidence of xanthinuria, stimulation of water intake is recommended. Because storage time significantly affected the incidence and amount of xanthine, xanthinuria present in stored samples should be re-evaluated in fresh urine. Because 80% of dogs with ultrasound reports presented with xanthine-uroliths and 43% of dogs with xanthine-uroliths on ultrasound developed clinical signs due to these uroliths, this study strongly encourages clinicians to perform an abdominal ultrasound if xanthinuria is detected.