Lowering serum urate levels to less than 6 mg/dL in patients with gout and stage 3 chronic kidney disease (CKD) is not associated with an increased risk of severe kidney progression, according to a cohort study.

The study, published in JAMA Internal Medicine, evaluated 14,792 patients aged 40–89 years with gout and stage 3 CKD. The cohort had a mean age of 73.1 years, with 62.3% male participants. Baseline characteristics included a mean serum urate level of 8.9 mg/dL and an estimated glomerular filtration rate (eGFR) of 49.9 mL/min/1.73 m². Nearly all participants (98.8%) were prescribed allopurinol, while 1.2% received febuxostat.

After five years, the risk of severe or end-stage kidney disease was 10.32% for those achieving the serum urate target of <6 mg/dL compared to 12.73% for those above the threshold. The adjusted hazard ratio (HR) was 0.89 (95% CI, 0.80–0.98), with a predefined noninferiority margin of 1.2. Additionally, the study reported a reduced risk of end-stage kidney disease alone (HR 0.67; 95% CI, 0.46–0.97).

Only 31.8% of participants achieved the target serum urate level within a year, with a median treatment duration of 243.5 days compared to 206.4 days among non-achievers. The study used a cloning, censoring, and weighting approach to emulate a randomized controlled trial, reducing potential bias.

Chronic kidney disease affects 20%-30% of patients with gout. This study provides evidence that lowering serum urate to recommended targets does not increase the risk of CKD progression. The findings are consistent with the treat-to-target approach endorsed by rheumatology societies.

The authors discuss potential biological mechanisms, including reduced glomerular pressure, anti-inflammatory effects, and preservation of endothelial function, as explanations for the observed outcomes. Further research could explore these mechanisms and assess long-term impacts on kidney function.

Conflict of interest disclosures can be found in the study.