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.

Keywords: Allopurinol; Dialysis; Gout; Pharmacokinetics; Urate.

Fig. 1

PRISMA 2020 flow diagram for scoping reviews

Fig. 2

The change in serum urate concentrations in gout patients receiving haemodialysis and allopurinol. The change in serum urate concentrations over a haemodialysis session for a study cohort (a) or individual patients (b). The change in serum urate concentrations over time (days) since commencement of dialysis for a study cohort (c) or individuals (d). For study cohorts, the mean ± SD is presented. The doses and frequency of dosing varied across the studies ^†400 mg allopurinol dose (daily for Johnson et al. [36], on non-dialysis days for Hayes et al. [37], POST dialysis session for Elion et al. [27]); ^£600–800 mg allopurinol dose PRE dialysis session [37];^†§400 mg allopurinol PRE dialysis session plus 600 mg POST dialysis session [29]; ^€250 mg/day allopurinol dose [13]; ^#600 mg allopurinol dose as 300 mg twice daily [28]; ^‡300 mg allopurinol dose POST session for Rutherford et al. [32], once daily for the remaining studies [29, 35]; ^¥≈100 mg/day allopurinol dose [22]; ^$200 mg/day allopurinol dose [29, 34, 36]; ^ǿ350 mg/day allopurinol dose [13]. Dashed lines indicate the target urate concentration of 0.36 mmol/L in absence of tophi