Urate-lowering drugs (ULDs) may be associated with the progression and recovery of chronic kidney disease (CKD) in patients with gout, according to study results published in Arthritis Research & Therapy.
To examine the risk for CKD in gout with ULDs, the study researchers included data from 5860 eligible patients with gout aged ≥18 years who had at least 1 prescription for a ULD from any of the Chang Gung Memorial Hospitals in Taiwan between 2012 and 2015.
Patient classification was based on the American Rheumatism Association classification criteria for acute gout. Patients were categorized according to their first ULD prescription as febuxostat users, allopurinol users, or uricosuric agent users. Exclusion criteria included patients prescribed 2 or more ULDs, patients with CKD stage 5 at the index date or with CKD stage progression to stage 5 between registration date and index date, and patients without data on serum creatinine levels.
Researchers assessed CKD progression and recovery using Cox proportional hazards models.
Mean age of patients at index date was 61.09±15.29 years (78.52% men). Chronic kidney disease stage 1 was reported in 1329 patients with gout (22.68%), CKD stage 2 in 1936 (33.04%), CKD stage 3 in 2018 (34.44%), and CKD stage 4 in 577 patients (9.85%).
Across 434,176 person-days of follow-up, CKD progression occurred in 741 patients, with an overall incidence rate of 1.70 per 1000 person-days. The incidence rates for CKD progression in allopurinol, febuxostat, and uricosuric agent users were 1.98, 1.88, and 1.64 per 1000 person-days, respectively.
Of the 741 patients with CKD progression who were followed for an additional 158,861 person-days, 571 (77.06%) had CKD recovery, with an overall incidence rate of 3.59 per 1000 person-days. The incidence rates for CKD recovery in allopurinol, febuxostat, and uricosuric agent users were 1.33, 6.21, and 3.53 per 1000 person-days, respectively.
Risk for CKD progression was 1.77 (95% CI, 0.85-1.76) in febuxostat and 1.37 (95% CI, 0.71-1.37) in uricosuric agent users compared with allopurinol users. Risk for CKD improvement was 1.43 in febuxostat users (95% CI, 1.26-1.62) and 1.00 in uricosuric agent users (95% CI, 0.88-1.14). Using Cox proportional hazard models, researchers indicated that compared with allopurinol users, the adjusted hazard ratio for CKD progression was 1.14 (95% CI, 0.80-1.66) in febuxostat users and 0.92 (0.67-1.31) in uricosuric agent users compared with allopurinol users.
Risk for CKD recovery was 2.17 (95% CI, 1.40-3.47) for febuxostat and 1.80 (1.20-2.83) for uricosuric agent exposure compared with allopurinol exposure. From the stratified analysis, it was indicated that compared with allopurinol users, febuxostat and uricosuric agent users were more likely to recover by a CKD stage in patients with CKD stages 3 and 4.
Overall, compared with allopurinol, febuxostat, and uricosuric agents were associated with a similar risk for CKD progression; CKD progression was not as common in patients exposed to febuxostat and uricosuric agents compared with patients who were exposed to allopurinol. In addition, compared with patients with gout receiving allopurinol, patients receiving febuxostat and uricosuric agents were 2-fold more likely to recover from CKD.
Study limitations included potential misclassification of patients with gout because of physician-based diagnoses, the existence of residual confounding, and the consideration of ULD prescriptions instead of patient consumption of the drugs.
“CKD progression in [patients with gout] was not an infrequent observation after the initiation of ULDs and renal function recovery was observed in three-quarters of those who had CKD progression,” the researchers concluded. “To the best of our knowledge, this is the first study to examine the risk of CKD progression and recovery in patients with gout after exposure to different classes of ULDs.”