Managing Gout in CKD Patients Save

A current review article addressed the management of gout patients with chronic kidney disease (CKD).  This full read review addresses the epidemiology, challenges, treatment decisions and outcomes. 

The prevalence of gout rises with each stage of CKD; from 4%, 6% to 10%, 11% to 13%, and >30% in CKD stages 1, 2, 3, and 4, respectively, Treating gout can be challenging, but more so in the presence of CKD where options may be limited or the risk of adverse outcomes rises. 

Who Needs Urate-Lowering Therapy?

Recommendations include these:

• ACR: "...with≥1 subcutaneous tophi, radiographic gout, or≥2 gout flares annually. ULT is not recommended for patients who are experiencing their first gout flare except for those with moderate-to-severe CKD (CKD stage≥3), SU > 9mg/dL, or urolithiasis."
• EULAR: "...patients with recurrent gout flares, tophi, urate arthropathy, and/or urolithiasis. They additionally recommend ULT after diagnosis in patients younger than 40 years or in patients with very high SU levels (>8.0mg/dL)"
• Review points:
  • If serum uric acid (SUA) target (<6) cannot be reached (despite allopurinol maximum dose  of 800 mg), allopurinol should be switched to febuxostat or a uricosuric or should be combined with a uricosuric. 
  • Uricosurics are not recommended for patients with CKD. 
  • Indefinite treatment is recommended 
  • ~39% of patients experience recurrence of gout when ULT is withdrawn

Sad facts from a Veterans Administration study:

• After receiving new allopurinol prescriptions, only 46% were given continuous prescriptions, and only 20% reached target SUA
• 24% of patients had SUA levels checked within 6 months
• 61% had no SU checked at all during the study period
• Of 127 patients on ULT but not achieving SUA target, only 37% had adjustments in allopurinol doses

 

Start-Low-Go-Slow Approach

This is attractive and advantageous for all, including CKD patients, as it reduces flares, toxcity, allopurinol hypersensitivity syndrome (AHS), and noncompliance. As suggested by Stamp et al, the dosing should be based on eGFR as shown below.

HLA-B∗5801 Testing and Allopurinol Hypersensitivity Syndrome

The allele HLA-B∗5801 allele is highly associated with AHS, especially in certain Asian populations, where the odds ratio is 580, 348.3, and 65.6 in Han Chinese,Thai, and Japanese patients.  In the United States, the prevalence of HLA-B∗5801 is 0.7% in Whites and Hispanics, 3.8% among African Americans, and 7.5% among Asians.

 

Other Urate-Lowering Therapies

Aside from allopurinol, there are other options:

• Febuxostat: as allopurinol is excreted by the kidneys, febuxostat is not. Febuxostat is metabolized in the liver. In CKD, the starting dose for febuxostat is 20-40mg daily,titrated to achieve target SUA up to 120mg per day. It is effective for lowering SUA and decreasing the incidence of gout flares in patients with CKD. But there are warnings and concerns about cardiac adverse events in gout patients on FEB. 
• Uricosuric Agents: are not recommended by the ACR as first-line ULT for patients with moderate-to-severe CKD (stage≥3). Probenecid has reduced efficacy and limited safety data in patients with CKD and is not recommended over xanthine oxidase inhibitors.
• Pegloticase: Renal dosage adjustment is not needed with PEG. However, allergic or infusion reactions can be minimized with the use of immunomodulators (methotrexate, mycophenolate mofetil, leflunomide, azathioprine) and these (especially MTX) may not be appropriate in the setting of CKD 

 

Gout Flares iWith CKD

• NSAIDs are contraindicated in CKD, treatments are limited to colchicine, oral steroids, or arthrocentesis and steroid injections.

 

Prophylaxis for Gout With CKD

• EULAR guidelines recommend prophylaxis during the first 6 months of ULT with colchicine, renal dosed as needed.
• CKD dosing: colchicine 0.6mg once daily in CKD stage 3 (CL_cr 30-60mL/min), and once every 2 to 3 days or 0.3mg daily in CKD stage 4 (CL_cr<30mL/min). Colchicine should be avoided in patients with CL_cr<10mL/min
• Half-dose reduction has also been advised for patients≥70 years of age

 

In 2020, 55.8 million people globally had gout, and this burden is estimated to reach 95.8 million by 2050.