Allopurinol Dosing With Gout and Dialysis

Allopurinol is a xanthine oxidase inhibitor and a first-line urate-lowering therapy. Hyperuricemia leads to gout, and the risk of gout increases as kidney function decreases. Therefore, the use of allopurinol is common among people with kidney failure receiving dialysis. However, little guidance exists regarding allopurinol prescribing for this population.

A scoping review by Noha A. Kamel and colleagues examined allopurinol dosing practices, the drug’s effectiveness at lowering the urate concentration, and the pharmacokinetics of oxypurinol (allopurinol’s active metabolite) among patients with gout receiving hemodialysis (HD) or peritoneal dialysis (PD). They searched the Ovid MEDLINE, Ovid Embase, EBSCOhost CINAHL, Scopus, and Web of Science databases from inception through October 19, 2023. Eighteen studies were identified for inclusion in the analysis, including case reports, case series, and short communications; reviews, abstracts, editorials, and protocols were excluded.

The study included a total of 390 patients; 274 (70%) were receiving HD and 116 (30%) were receiving PD. Most patients were male and White, but not all studies reported gender and race and ethnicity.

The researchers observed that allopurinol dose requirements differ by dialysis modality. Doses were higher among patients undergoing HD (100-600 mg/d) than among those undergoing PD (110-125 mg/d). An average dose of 121±62 mg/d achieved target serum urate concentrations (<0.36 mmol/L) among 61% of patients receiving HD. Among patients receiving PD, an average dose of 110±72 mg/d resulted in 47% of patients achieving the target. Gout flares decreased from 2 to 0.1 per year among patients receiving dialysis.

Urate and oxypurinol were removed at similar rates in each modality, but clearances were much higher with HD than with PD. Peritoneal dialytic clearance of oxypurinol was 3.14 mL/min and clearance of urate was 2.7 to 4 mL/min. Hemodialytic clearance of oxypurinol was 78 to 137 mL/min and clearance of urate was 80 to 165 mL/min.

Hemodialysis decreased oxypurinol concentrations by 39% to 57% and urate concentrations by 56% to 71%. Over time (1-230 days), HD reduced urate concentrations by 14% to 41%.

The authors acknowledged the difficulty of allopurinol dosing for patients with gout receiving dialysis because dialysis clears both urate and oxypurinol from the body. However, they recommended the following approaches, which are consistent with practice for patients with gout who are not receiving dialysis:

• Dosing after HD sessions
• Escalation of doses until the serum urate target is achieved
• Prophylaxis when dialysis is started to prevent gout flares

Additional research is needed “to determine the dialysis conditions that contribute to variability in response to allopurinol to inform dose individualisation,” they said. “Quantification of these factors, using a modelling and simulation approach, can assist in identifying optimal allopurinol dosing strategies in different dialysis populations.”

Source: Journal of Nephrology