Dosing practices, pharmacokinetics, and effectiveness of allopurinol in gout patients receiving dialysis: a scoping review.

Abstract

Urate and oxypurinol, allopurinol's active metabolite, are predominantly eliminated by the kidneys. Therefore, optimising allopurinol dosing in patients on dialysis is challenging. This review explores allopurinol dosing practices, oxypurinol pharmacokinetics, and effectiveness in gout patients receiving haemodialysis or peritoneal dialysis (PD). Five databases and grey literature were searched. Studies on gout patients on allopurinol, receiving dialysis, and reporting dosing, pharmacokinetics, or effectiveness (reduction in urate and/or gout flares) were included. Abstract, full text screening and data extraction were done by two authors. Studies were grouped by dialysis modality. Eighteen studies were identified including 390 patients, most (n = 274, 70%) on haemodialysis with allopurinol administered after dialysis. The peritoneal dialytic clearance of oxypurinol (3.14 mL/min, n = 5) and urate (2.7-4 mL/min, n = 25) was similar. The haemodialytic clearance was 78-137 mL/min for oxypurinol (n = 21) and 80-165 mL/min for urate (n = 19). Allopurinol doses were higher in haemodialysis (100-600 mg/day) than PD (110-125 mg/day). Haemodialysis sessions decreased oxypurinol and urate concentrations by 39-57% (n = 30) and 56-71% (n = 6), respectively. Over time (1-230 days), urate concentrations in haemodialysis (n = 85) reduced by 14-41%. Target serum urate (< 0.36 mmol/L) was achieved in 61% (20/33) and 47% (13/28) of haemodialysis and PD patients, respectively. Gout flares decreased from 2 to 0.1 attacks/year in patients receiving dialysis (n = 79). Oxypurinol and urate clearance by haemodialysis was higher than PD, necessitating higher doses of allopurinol. POST dialysis allopurinol doses titrated to target urate are suggested. Future studies considering the impact of dialysis modality on allopurinol dose requirements are needed.