Gout Medicines in Kidney Disease

Gout is common in chronic kidney disease because urate excretion falls, and treatment is limited because NSAIDs and full-dose colchicine are unsafe. Acute attacks are treated with the least harmful agent, and urate lowering therapy is started low and increased slowly to a target.

Targets. Serum urate under 360 micromol/L (6 mg/dL), and under 300 micromol/L (5 mg/dL) with tophi.

Contributors. Loop and thiazide diuretics, aspirin and ciclosporin raise urate, while losartan lowers it.

Acute attack.

• Prednisolone 30 to 40 mg orally once daily for 5 days, with glucose monitoring, is first line in chronic kidney disease.

• Colchicine is possible at reduced dose.

• Intra-articular corticosteroid for one or two joints.

• Avoid NSAIDs. Anakinra 100 mg subcutaneously daily for 3 days is a specialist option.

Urate lowering. Allopurinol first line. Febuxostat when allopurinol is not tolerated. Avoid probenecid when clearance is under 50 mL/min.

Special groups.

• Pregnancy: specialist advice, because data for allopurinol and febuxostat are limited.

• Older adults: lower colchicine and allopurinol doses.

• Dialysis: allopurinol is dialysed, so dose after the session.

• East Africa: HLA-B*58:01 testing, which predicts allopurinol hypersensitivity, may not be available, so start at the lowest dose and warn the patient about rash.

• Colchicine, acute: 0.5 mg orally for a single dose when clearance is under 30 mL/min, with no repeat within 14 days. At clearance 30 or over, 1 mg then 0.5 mg after 1 hour, maximum 1.5 mg on the first day. Avoid with clarithromycin, ciclosporin and strong CYP3A4 or P-glycoprotein inhibitors.

• Colchicine, prophylaxis: 0.5 mg once daily at eGFR 30 or over, 0.5 mg on alternate days at 15 to 29, and avoid under 15 except by specialist decision, for 3 to 6 months after starting urate lowering.

• Allopurinol: start 50 mg once daily in chronic kidney disease, increase by 50 to 100 mg every 2 to 5 weeks to the urate target. Doses over 300 mg daily can be used with monitoring, maximum 900 mg daily.

• Febuxostat: 40 mg once daily, increased to 80 mg after 2 to 4 weeks if urate is over 360 micromol/L. Boxed warning for cardiovascular death, so avoid in established cardiovascular disease unless other options fail.

• Azathioprine or mercaptopurine with allopurinol: reduce the azathioprine dose to one quarter to one third, or avoid the combination.

Monitoring. Check urate every 2 to 4 weeks during titration, then every 6 months, and check creatinine, liver function, full blood count and rash.

Stop rules. Stop allopurinol at once for rash, fever, eosinophilia or liver or kidney injury. Do not rechallenge after a severe reaction.

Referral and escalation. Refer for urate not at target on maximum tolerated allopurinol, tophaceous disease, frequent attacks, or when anakinra or pegloticase is considered.

Common errors. Starting allopurinol at 100 mg or more, prescribing NSAIDs or repeated colchicine doses, and giving prophylaxis for too short a period.