Should a 73-year-old patient with Chronic Kidney Disease (CKD) and impaired renal function, currently on allopurinol (300mg), taper their dose?

Allopurinol Dosing in CKD 4 with eGFR 20

Yes, the 73-year-old patient with CKD 4 (eGFR 20) should have their allopurinol dose adjusted, but not necessarily tapered if they are tolerating the current dose without adverse effects.

Assessment of Current Situation

The patient is currently on allopurinol 300 mg daily with no reported adverse effects, which is important to note. However, according to current guidelines, allopurinol dosing should be adjusted based on renal function:

• In patients with renal impairment, allopurinol's active metabolite (oxipurinol) accumulates due to decreased clearance 1
• This accumulation can increase the risk of severe cutaneous adverse reactions (SCARs), which have a high mortality rate (25-30%) 2
• The FDA label specifically states that "patients with decreased renal function require lower doses of allopurinol tablets than those with normal renal function" 3

Recommended Approach

1. Dose adjustment rather than complete discontinuation:

   • Since the patient is tolerating the medication without ill effects, abrupt discontinuation is not necessary
   • However, the dose should be adjusted according to creatinine clearance 2
   • For patients with eGFR 20, a reduced dose is appropriate to minimize risk while maintaining efficacy

2. Recommended dosing strategy:

   • Start with a lower dose (50-100 mg daily) 1, 3
   • Monitor serum uric acid levels and renal function
   • Titrate dose upward as needed to achieve target serum urate level <6 mg/dL 2
   • The maximum dose should be adjusted according to creatinine clearance 2

3. Monitoring parameters:

   • Serum uric acid levels every 2-4 weeks during dose adjustment
   • Renal function (BUN, creatinine)
   • Signs of hypersensitivity reactions (rash, fever, eosinophilia)
   • Liver function tests

Alternative Options

If target uric acid levels cannot be achieved with the adjusted allopurinol dose:

1. Consider febuxostat:

   • Febuxostat has been found more effective in patients with CKD than allopurinol given at doses adjusted to creatinine clearance 2, 4
   • Start at 40 mg daily 1
   • A 2020 study showed that febuxostat may have a protective effect on kidney function in CKD patients 4

2. Consider benzbromarone:

   • Can be used in patients with moderate renal impairment 2
   • Not recommended for use in patients with eGFR <30 mL/min 2

Potential Benefits of Continuing Treatment

Despite the need for dose adjustment, there are potential benefits to maintaining the patient on appropriate urate-lowering therapy:

• Some studies suggest allopurinol may slow the progression of CKD 5, 6, 7
• Allopurinol treatment has been associated with reduced cardiovascular risk in CKD patients 6, 7

However, it's important to note that a more recent randomized controlled trial (CKD-FIX) found that allopurinol did not slow the decline in eGFR compared to placebo in patients with CKD at high risk of progression 8.

Conclusion

For this 73-year-old patient with CKD 4 (eGFR 20) who is currently on allopurinol 300 mg with no ill effects:

• Reduce the dose based on creatinine clearance rather than completely tapering off
• Monitor serum uric acid levels and renal function regularly
• If target uric acid levels cannot be achieved with adjusted allopurinol dosing, consider switching to febuxostat