Allopurinol Therapy in Chronic Kidney Disease

Introduction to Allopurinol Therapy

The American College of Rheumatology recommends starting with lower doses of allopurinol in patients with renal impairment, such as 50 mg daily for patients with stage 4 or worse CKD, to minimize risks while maintaining efficacy 1, 2, 3
Target serum urate level should be <6 mg/dL, and dose can be titrated above 300 mg daily if needed to achieve target urate levels, even in CKD patients, with appropriate risk management 1, 2, 4

The guideline recommends gradually increasing the dose by 100 mg increments every 2-5 weeks, and monitoring serum uric acid levels after 2-4 weeks of each dose adjustment, although the exact monitoring schedule may vary 1, 2, 4
Regular monitoring of renal function (BUN, creatinine, creatinine clearance) and signs of hypersensitivity reactions (rash, fever, eosinophilia) is essential, with the strength of evidence for this recommendation being based on expert opinion 1, 2, 3
Consider HLA-B*5801 screening in high-risk populations, such as Korean patients with stage 3 or worse CKD, and patients of Han Chinese and Thai descent, with a moderate level of evidence supporting this recommendation 1, 2

Azathioprine/mercaptopurine dose should be reduced by 65-75% when co-administered with allopurinol, due to increased risk of toxicity, with a high level of evidence supporting this recommendation 5
Thiazide diuretics may enhance allopurinol toxicity, and anticoagulants like dicumarol may have their half-life prolonged by allopurinol, with a moderate level of evidence supporting these recommendations 5

Febuxostat can be considered as an alternative to allopurinol, starting at 40 mg daily, with a moderate level of evidence supporting its use in CKD patients, although long-term comparative studies with allopurinol are limited 1, 2, 3
Uricosuric agents like probenecid may be used in patients with normal renal function, although their use in CKD patients is not well established, with a low level of evidence supporting this recommendation 1, 2, 6
Benzbromarone can be used in patients with moderate renal impairment, but is not recommended for use in patients with eGFR <30 mL/min 2
Pegloticase is reserved for severe, refractory cases after failure of properly dosed oral medications, as per the ACR 2, 4

Avoid rapid dose escalation, as it increases the risk of hypersensitivity reactions, with a high level of evidence supporting this recommendation, based on studies of allopurinol use in CKD patients 1, 2
Consider colchicine or low-dose prednisone when initiating therapy to prevent acute gout flares, with a moderate level of evidence supporting this recommendation, based on expert opinion and clinical experience 1, 2, 4
The American College of Rheumatology (ACR) recommends adjusting allopurinol dosing based on renal function to minimize the risk of severe cutaneous adverse reactions (SCARs), which have a high mortality rate (25-30%) 2, 1
Gout management in patients with chronic kidney disease (CKD) involves the use of urate-lowering therapy (ULT), with allopurinol being the preferred first-line treatment, as recommended by the ACR with a high strength of evidence 3, 1

The ACR and European League Against Rheumatism (EULAR) guidelines strongly recommend colchicine as a first-line option for acute gout flare management, with a low-dose regimen of 1.2 mg initially, followed by 0.6 mg one hour later, and continued with 0.6 mg once or twice daily until flare resolves 2
The ACR and EULAR guidelines also recommend NSAIDs with proton pump inhibitor if appropriate, and corticosteroids, either oral (30-35 mg/day of prednisolone for 3-5 days) or intra-articular injection, as first-line options for acute gout flare management 2, 4
Intra-articular corticosteroids are a good alternative for patients with contraindications to colchicine, as stated by the American College of Physicians 7

Dietary modifications, such as limiting alcohol, meats, and high-fructose corn syrup intake, are recommended for CKD patients with gout, according to the American Journal of Kidney Diseases 8
Adequate hydration (2.5-3 L fluid intake per day) should accompany allopurinol therapy to optimize uric acid clearance, as suggested by the Annals of Oncology 9

Allopurinol can be safely used to treat gout in patients with Chronic Lymphocytic Leukemia (CLL) and is recommended for these patients, particularly when they are at risk for tumor lysis syndrome or hyperuricemia, as per the Journal of Clinical Oncology and Annals of Oncology 5, 9
Oxipurinol, the active metabolite of allopurinol, accumulates in renal failure, which may enhance efficacy at lower doses, although this requires careful monitoring and dose adjustment 4