Should I prescribe Urate-Lowering Therapy (ULT) for all patients with Chronic Kidney Disease (CKD) and hyperuricemia, regardless of gout history?

ULT for CKD Patients with Hyperuricemia Without Gout

ULT is conditionally recommended against for patients with asymptomatic hyperuricemia (serum urate >6.8 mg/dl) and CKD without gout, except in specific circumstances. 1

Evidence-Based Recommendations

• For patients with asymptomatic hyperuricemia (serum urate >6.8 mg/dl) without prior gout flares or subcutaneous tophi, the American College of Rheumatology (ACR) conditionally recommends against initiating ULT, regardless of CKD status 1

• However, there are specific exceptions where ULT may be considered in CKD patients with hyperuricemia:

  • Patients experiencing their first gout flare with CKD stage ≥3 1
  • Patients with serum urate >9 mg/dl 1
  • Patients with urolithiasis 1

Treatment Algorithm for CKD Patients with Hyperuricemia

1. For CKD patients with hyperuricemia WITHOUT gout history:

   • Monitor serum urate levels regularly 1
   • Do not initiate ULT unless specific risk factors are present (CKD stage ≥3 with first gout flare, SU >9 mg/dl, or urolithiasis) 1

2. For CKD patients with hyperuricemia WITH gout history:

   • Strongly recommend ULT if any of the following are present:
     • Frequent gout flares (≥2/year) 1
     • One or more subcutaneous tophi 1
     • Radiographic damage attributable to gout 1
   • Conditionally recommend ULT if:
     • Patient has experienced >1 flare but has infrequent flares (<2/year) 1
     • First flare with CKD stage ≥3 1

Medication Selection When ULT is Indicated

• Allopurinol is strongly recommended as the preferred first-line agent for all patients, including those with CKD stage >3 1
• Start at a low dose with subsequent dose titration to target (e.g., <100 mg/day and lower in patients with CKD for allopurinol) 1, 2
• A xanthine oxidase inhibitor (allopurinol or febuxostat) is strongly recommended over probenecid for those with CKD stage >3 1
• Always initiate concomitant anti-inflammatory prophylaxis therapy (colchicine, NSAIDs, or prednisone/prednisolone) when starting ULT 1

Important Caveats and Pitfalls

• Despite the association between hyperuricemia and CKD progression, current evidence from meta-analyses does not consistently support renoprotective effects of ULT in CKD patients with asymptomatic hyperuricemia 3, 4
• Febuxostat may be more effective than allopurinol at lowering urate levels in CKD patients (MD: -1.547; 95% CrI: -2.473 to -0.626) 3, but this alone is not an indication for treatment
• When initiating ULT in CKD patients, be aware of potential drug interactions and the need for dose adjustments 2
• Patients with G6PD deficiency should not receive pegloticase due to risk of hemolysis and methemoglobinemia 5
• Monitor for adverse effects of ULT, particularly during initiation and dose titration phases 1

Despite some evidence suggesting potential renoprotective effects of ULT in CKD patients with hyperuricemia 6, 7, the current ACR guidelines do not support initiating ULT solely for asymptomatic hyperuricemia in CKD patients without a history of gout 1.