Hyperuricemia and Gout in Chronic Kidney Disease

Background

• Hyperuricemia (serum urate concentration ≥ 7 mg/dL [420 mcmol/L]) and gout (inflammatory arthritis resulting from deposition of monosodium urate crystals in joint fluid and other tissues) are common comorbidities in patients with chronic kidney disease (CKD).
• CKD can result in hyperuricemia. Since two-thirds of urate excretion occurs through the kidneys, impaired renal function is associated with hyperuricemia and increased risk of gout.
• Additionally, hyperuricemia may also be associated with progression of kidney disease.
• Prevalence of CKD and gout is higher in males and in older age. Postmenopausal females have uric acid levels close to age-matched males
• Isolated asymptomatic hyperuricemia is not clinically significant on its own, but when serum urate level is > 7 mg/dL (420 mcmol/L) there is increased likelihood of crystal deposition which may result in gout.

Evaluation

• Acute gout usually presents as sudden onset of joint tenderness, erythema, warmth, and swelling accompanied by extreme pain. It is often monoarticular and frequently involves the first metatarsophalangeal joint (podagra).
• Advanced gout is characterized by subcutaneous nodules in soft tissues (tophi) and/or persistently stiff or swollen joints and typically presents in the setting of years of recurrent gouty attacks.
• Diagnosis is often based on presentation and physical exam. Testing may include serum uric acid level (although it may be lower during an attack), synovial fluid analysis, and imaging such as x-ray, ultrasound, or computed tomography (CT) scan; consider joint fluid aspiration with culture and blood culture if there is suspicion of septic arthritis.
• The presence of a normal serum urate level does not exclude the possibility of acute gouty arthritis. Demonstration of urate crystals in synovial fluid analysis or in a tophus by polarized light microscopy confirms the diagnosis of gout (Strong recommendation).
• If identification of crystals is not possible, the diagnosis of gout can be supported by classical clinical features such as podagra, tophi, rapid response to colchicine, and/or characteristic imaging findings (Weak recommendation).

Management

• The overall goals for treating gout in patients with chronic kidney disease (CKD) are similar to those in patients with normal renal function but have important differences in specific management:
  • treat acute attack
  • prevent recurrent attacks with urate-lowering therapy (ULT)
  • prevent or reverse complications resulting from deposition of monosodium urate crystals in joints, kidneys, or other sites
• Pharmacological treatment of asymptomatic hyperuricemia is not recommended to prevent gouty arthritis, renal disease, or cardiovascular events (Weak recommendation).
• Presence of CKD influences management of gout:
  • CKD in a patient with gout is an indication for ULT.
  • Choice and dosage of medications for acute flares and urate lowering depend on renal function.
  • In patients on dialysis, use most drug classes at modified doses (uricosuric agents are contraindicated).
• Management of acute gout flares:
  • Consider treating acute flares with pharmacologic therapy (Strong recommendation).
  • Treatment options include:
    • colchicine
      • as first-line therapy in patients with normal renal function (Strong recommendation)
      • consider dose reduction in patients with moderate kidney disease
      • avoid in patients with severe kidney disease (Strong recommendation)
    • nonsteroidal anti-inflammatory drugs (NSAIDs)
      • alternative first-line therapy in patients with normal renal function (Strong recommendation)
      • avoid in patients with moderate or severe renal impairment (Strong recommendation)
    • corticosteroids
      • oral corticosteroids can be used as first-line therapy in patients with acute gout flares (Strong recommendation)
      • first line of therapy in patients with CKD (Strong recommendation)
      • dose adjustment not required in patients with CKD or on dialysis
    • interleukin-1 (IL-1) inhibitors in patients with frequent flares who have contraindications or are refractory to other first-line therapy
      • canakinumab (Strong recommendation), no dose reduction needed in patients with CKD
      • anakinra (Weak recommendation) with dose reduction in patients with creatinine clearance < 30 mL/minute
  • Initiate treatment as early as possible (Strong recommendation).
  • Medications should be initiated at high dose and tapered gradually.
  • Treat for 7-14 days until flare resolves.
  • Consider nonpharmacologic treatments in addition to medication, including rest, ice packs, and elevation of affected joints (Weak recommendation).
  • Educate patients about pathophysiology of the disease, available treatment, and treatment objectives (Strong recommendation).
• ULT (such as allopurinol) is indicated in patients with recurrent flares, tophi, urate arthropathy, and/or renal stones (Strong recommendation).
  • Hyperuricemia associated with increased risk of all-cause and cardiovascular disease-related mortality in patients with CKD.
  • ULT can be used in patients with CKD and normal dosing is considered safe.
  • Initiate ULT close to first diagnosis of hyperuricemia in patients with CKD (Strong recommendation).
  • Use low-dose ULT initially and titrate dose to achieve target serum urate levels (Weak recommendation).
  • Continue ULT indefinitely to maintain serum uric acid level < 6 mg/dL (360 mcmol/L) (Weak recommendation).
  • Discuss benefits, harms, costs, patient preference, and concomitant prophylaxis against flare before initiation of ULT in patients with recurrent gout attacks (Strong recommendation).
  • ULT may not affect mortality or progression to end-stage renal disease in patients with CKD
• Prophylaxis for prevention of acute gout flares is suggested during initiation ULT (Strong recommendation).
  • Initiate concomitant prophylaxis in patients starting ULT (Strong recommendation).
  • Suggested anti-inflammatory prophylaxis regimens include the same medications used to treat acute gout flares, including:
    • low-dose colchicine as first-line therapy (Strong recommendation)
    • low-dose NSAIDs with gastroprotection if needed as alternative first-line therapy (Weak recommendation); avoid in patients with CKD (estimated GFR < 60 mL/minute/1.73 m²)
    • low-dose corticosteroids in patients with intolerance or resistance to colchicine and NSAIDs (Weak recommendation)
  • Continue prophylaxis for:
    • first 6 months of ULT (Weak recommendation)
    • 3-6 months after target serum urate levels are reached in patients who develop gout, depending on the nature of gout signs and symptoms during ULT (Strong Recommendation)
• Advise diet and lifestyle modifications (Weak recommendation).
• Consultation with a nephrologist and a rheumatologist maybe helpful for optimal management of gouty arthritis in patients with CKD.