Study: CKD Not Worsened With Gout Treatment

Worries that urate-lowering therapy (ULT) could speed renal failure in patients with gout and chronic kidney disease (CKD) are unfounded, data from Great Britain indicated.

In a so-called “target trial emulation” analysis of nearly 15,000 Britons, the 5-year likelihood of CKD progressing to severe or end-stage renal disease (ESRD) was estimated to be 10.32% for patients achieving the standard serum urate target of

That yielded a hazard ratio of 0.89 (95% CI 0.80-0.98) for CKD progression with successful ULT, easily meeting prespecified noninferiority criteria and suggesting an actual renal benefit, the researchers reported in JAMA Internal Medicine.

“These findings support optimizing ULT to achieve target serum urate levels when treating patients with gout and impaired kidney function,” Wei and colleagues concluded.

Some 20% to 30% of gout patients also have CKD, the researchers said, which is not surprising since they share many risk factors (age, obesity, hypertension, heavy drinking). Thus the question of whether treatment for one may worsen the other is highly pertinent.

Scientific evidence regarding ULT’s safety in patients with comorbid CKD has generally found no problem, the group observed. Nevertheless, “some clinicians opt to withhold, reduce, or even discontinue ULT when a patient with gout experiences a decline in kidney function, complicating gout management.”

“This practice, often reported anecdotally by rheumatologists who note that ‘nephrologists keep lowering my patient’s allopurinol for no reason,’ contributes to public health concerns regarding the potential risks of ULT, including the rare but serious risk of allopurinol hypersensitivity syndrome,” Wei and colleagues continued. “Addressing this issue is crucial for the timely and effective management of CKD progression and gout.”

For the current study, the investigators drew on the IQVIA Medical Research Database, which collects patients’ general practice records in the U.K. Their search identified 14,792 patients with both gout and moderate CKD (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m²) treated from 2000 to 2023, who had at least 1 year of management.

Rather than simply examine renal outcomes in these patients according to their serum urate trajectories, the researchers used the data to perform a simulated randomized trial. As Wei and colleagues explained, it involved “cloning, censoring, and weighting” the data, such that one patient’s records could be used in different analytical iterations.

Mean patient age in the sample was about 73, and men comprised 62%. Baseline serum urate averaged 8.9 mg/dL (SD 1.6). Besides CKD, other comorbidities such as hypertension, diabetes, and atrial fibrillation were common; and as a consequence, many patients were taking medications other than those for gout and CKD. Nearly 99% of patients on ULT were using allopurinol, while the remainder were taking febuxostat (Uloric). Mean follow-up was just over 3 years.

Progression to severe CKD or ESRD was defined as any of the following:

• Two eGFR measurements below 30 mL/min/1.73 m² at least 90 days apart within 1 year
• Codes for CKD stage 4 or 5
• Commencing hemodialysis or peritoneal dialysis
• Kidney transplant

When the researchers looked at ESRD alone (CKD stage 5, dialysis, or transplant) as the outcome of interest, the analysis showed risks of 1.10% for patients achieving the target urate level versus 1.73% for those with urate above 6 mg/dL, for a hazard ratio of 0.67 (95% CI 0.46-0.97).

Limitations to the study included that it was basically a modeling study, albeit with real-world patient data. Also, the potential for unmeasured confounders to influence the results cannot be ruled out. Wei and colleagues noted that patients achieving their urate goal “may have received better healthcare” overall, with greater adherence to ULT and all their medications, and therefore could have enjoyed superior renal outcomes as a result.