Urate-Lowering Therapy Remains Tolerable in Patients with Gout, CKD

Jie Wei, PhD

Credit: ResearchGate

Targeting urate-lowering therapy (ULT) to achieve serum urate levels ≤6 mg/dL did not elevate the risk of severe or end-stage kidney disease progression in patients with gout and chronic kidney disease (CKD) stage 3, according to a new cohort study in JAMA Internal Medicine.¹

“Our study contributes to the limited literature on therapeutic strategies for patients with gout and impaired kidney function,” wrote the investigative team, led by Jie Wei, PhD and Guangua Lei, MD, PhD, department of orthopedics, Xiangya Hospital, Central South University. “Our findings suggest that lowering serum urate levels to ≤6 mg/dL is generally well tolerated and may even slow CKD progression in these individuals.”

Flares of gout are linked to severe pain, poor quality of life, and a transient increase in major cardiovascular and venous thrombotic events.² Hyperuricemia is a relevant causal risk for gout, with experts proposing optimal ULT administration as a standard-of-care option for long-term gout management.³

Achieving a target serum urate level (TSUL) of ≤6 mg/dL successfully reduced long-term gout flares and improved overall outcomes in recent trial-based evidence, with rheumatological societies, including the American College of Rheumatology (ACR), endorsing the treat-to-target approach.⁴

However, clinicians have remained cautious with ULT, with fewer than 30% of patients achieving TSUL in clinical general practice where most patients with gout are treated.⁵ In particular, with the frequent presence of CKD in gout, clinicians are concerned about the risk of progression to severe or end-stage kidney disease despite the lack of clear evidence.

In this study, Wei and colleagues examined the link between achievement of TSUL with ULT and the risk of severe or end-stage kidney disease progression in patients with impaired kidney function who developed gout.¹ This study, built on a target trial emulation approach, collected data from the IQVIA Medical Research Database between 2000 and 2023.

Investigators included participants aged 40 to 89 years with gout and CKD stage 3, who had ≥1 year of continuous general practice enrollment before entering the analysis. Overall, 34,458 eligible individuals met the inclusion criteria and initiated ULT during the study period.

Primary outcomes for the analysis included severe or end-stage kidney disease, defined by an estimated glomerular filtrate rate (eGFR) of <30 mL/min/1.73 m2 on ≥2 occasions more than 90 days apart within 1 year, or ≥1 code for CKD stages 4 or 5, hemodialysis, peritoneal dialysis, or kidney transplant. Based on evidence from previous randomized controlled trials (RCTs), the noninferiority margin of the hazard ratio (HR) was set at 1.2 comparing individuals who lowered their serum urate levels to 6 mg/dL versus those who did not.

Among those who met the inclusion criteria, the primary analysis included 14,792 participants (mean age, 73.1 years; 9215 men [62.3%] and 5577 women [37.7%]) with gout and CKD stage 3. Of those who initiated ULT, 4706 (31.8%) achieved TSUL within 1 year of the index date.

Upon analysis, the 5-year risk of severe or end-stage kidney disease was 10.32% for those who achieved the target serum urate level and 12.73% for those who did not meet the goal. In comparison with those who did not achieve target levels, the adjusted 5-year risk difference and HR of severe or end-stage kidney disease for patients achieving TSUL was –2.41% (95% CI, –4.61 to –0.21) and 0.89 (95% CI, 0.80 to 0.98), respectively.

In their summary, Wei and colleagues indicated if future analyses corroborate these findings, a reassessment of the risk-benefit ratio for ULT in patients with gout and CKD may be necessary.

“Initiatives to optimize the use and adherence to ULT could benefit clinicians and patients,” Wei and colleagues wrote. “Furthermore, our study raises an important question about whether the risk-benefit assessment of a treat-to-target approach with ULT should be reevaluated for patients with gout and CKD in light of this evidence.”

References

1. _{Wang Y, Dalbeth N, Terkeltaub R, et al. Target Serum Urate Achievement and Chronic Kidney Disease Progression in Patients With Gout and Kidney Disease. JAMA Intern Med. Published online November 25, 2024. doi:10.1001/jamainternmed.2024.6212}
2. _{Cipolletta E, Tata LJ, Nakafero G, Avery AJ, Mamas MA, Abhishek A. Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA. 2022 Aug 2;328(5):440-450. doi: 10.1001/jama.2022.11390. PMID: 35916846; PMCID: PMC9346550.}
3. _{Doherty M, Jenkins W, Richardson H, Sarmanova A, Abhishek A, Ashton D, Barclay C, Doherty S, Duley L, Hatton R, Rees F, Stevenson M, Zhang W. Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet. 2018 Oct 20;392(10156):1403-1412. doi: 10.1016/S0140-6736(18)32158-5. PMID: 30343856; PMCID: PMC6196879.}
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5. _{Terkeltaub R. Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review. Drugs. 2023 Nov;83(16):1501-1521. doi: 10.1007/s40265-023-01944-y. Epub 2023 Oct 11. PMID: 37819612.}