What are the next steps in managing an 85-year-old Nepalese American male with a history of Hypertension (HTN), Type 2 Diabetes Mellitus (DM2), Heart Failure with preserved Ejection Fraction (HFpEF), Pulmonary Hypertension (pHTN), Chronic Kidney Disease stage 3a (CKD 3a) with microalbuminuria and impaired renal function, and gout, who has been started on Allopurinol (allopurinol) 50mg every other day, with a decrease in uric acid levels from hyperuricemia to 7.9, and what is the maximum dose of Allopurinol (allopurinol) in the setting of his Chronic Kidney Disease (CKD)?

From the Guidelines

The next step in gout management for this 85-year-old Nepalese American male with CKD 3a and an eGFR of 20 would be to continue titrating allopurinol with the goal of reaching a serum uric acid level below 6 mg/dL, starting with a dose increase to 50 mg daily, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. The patient's uric acid level has only decreased from 8.4 to 7.9 mg/dL on allopurinol 50 mg every other day, indicating the need for dose escalation.

• The dose should be increased gradually to 50 mg daily, then to 100 mg daily as tolerated, with monthly monitoring of uric acid levels and renal function.
• In the setting of his CKD with eGFR of 20, the maximum recommended allopurinol dose would be 200 mg daily, as lower doses are recommended in patients with CKD stage ≥3, according to the 2020 American College of Rheumatology guideline 1.
• Dose adjustments should be made slowly (every 2-4 weeks) to minimize the risk of allopurinol hypersensitivity syndrome, which is more common in patients with renal impairment.
• Regular monitoring of complete blood count, liver function, and renal function is essential during dose titration, as recommended by the 2012 American College of Rheumatology guidelines for management of gout 1.
• Adequate hydration should be encouraged, and concurrent medications that might affect uric acid levels or interact with allopurinol should be reviewed.
• If the target uric acid level cannot be achieved with allopurinol alone or if the patient experiences adverse effects, febuxostat could be considered as an alternative, though it requires careful monitoring in patients with severe renal impairment.

From the FDA Drug Label

The dose of allopurinol tablets recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent Since allopurinol tablets and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol tablets should consequently be reduced With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable. When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg.

The patient's eGFR is 20, which corresponds to a creatinine clearance of 10 to 20 mL/min.

• The max dose of allopurinol in this setting is 200 mg daily 2.
• The patient is currently taking 50mg every other day, which is lower than the recommended dose.
• The next step in management would be to increase the dose to achieve a serum uric acid level of 6 mg/dL or less, without exceeding the maximal recommended dosage of 200 mg daily in this patient with CKD.
• The dose can be increased by 50-100 mg every week, as tolerated, and as guided by serum uric acid levels.

From the Research

Management of Hyperuricemia in CKD

• The patient has a history of gout and is currently being treated with allopurinol 50mg every other day, with a uric acid level decrease from 8.4 to 7.9 3, 4.
• The maximum dose of allopurinol in the setting of CKD is not strictly defined, but studies suggest that increasing the dose above the proposed creatinine clearance-based dose can be effective and safe in patients with chronic gout, including those with renal impairment 4.
• However, the starting dose of allopurinol is a risk factor for allopurinol hypersensitivity syndrome, and a proposed safe starting dose is 1.5 mg per unit of estimated GFR 5.

Alternative Treatment Options

• Febuxostat is a novel xanthine oxidase inhibitor that has been shown to be effective in reducing serum uric acid levels and slowing the progression of renal disease in patients with CKD 3, 6.
• Febuxostat may be a suitable alternative for patients who are refractory to allopurinol or experience adverse effects 7.
• The long-term use of febuxostat may exert a protective effect on the kidneys, and it is generally well-tolerated by patients with CKD and hyperuricemia 6, 7.

Dosing Considerations

• The dose of allopurinol can be gradually increased to achieve the target serum urate level, but the risk of hypersensitivity syndrome should be carefully monitored 5.
• Febuxostat can be initiated at a dose of 40mg, and its effectiveness in reducing serum uric acid levels has been demonstrated in patients with CKD 6, 7.
• The choice of treatment and dosing strategy should be individualized based on the patient's renal function, medical history, and response to treatment 3, 4, 6, 7.