I‐Wen Ting

Background: Direct comparisons of the effectiveness of allopurinol with that of other urate-lowering agents in chronic kidney disease (CKD) populations, as well as guideline recommendations for clinical practice, are lacking. Methods: We constructed a pharmacoepidemiology cohort study by including patients from Taiwan's long-term integrated CKD care program to compare the effectiveness among allopurinol, febuxostat and benzbromarone in reducing the risk of progression to dialysis. A total of 874 patients with hyperuricemia who were newly treated with allopurinol, febuxostat or benzbromarone were included. The primary and secondary outcomes were incident end-stage renal disease (ESRD) and the serum uric acid (SUA) changes from baseline, respectively. The results were analyzed using multiple Cox proportional models adjusted for multinomial propensity scores. For subgroup analyses, we further stratified patients according to whether their latest SUA level reached the therapeutic target. Results: Compared with allopurinol, benzbromarone therapy was associated with a reduced risk of progression to dialysis, the adjusted hazard ratio was 0.50 (95% confidence interval, 0.25-0.99). Patients who received allopurinol or febuxostat exhibited a comparable risk of ESRD [adjusted hazard ratio, 0.99 (0.40-2.44)]. Febuxostat was significantly more potent than allopurinol or benzbromarone in lowering SUA levels in the fully adjusted model. Among patients who reached the therapeutic target, those with febuxostat and benzbromarone initiation had a significantly lower risk of ESRD. Conclusions: In conclusion, compared with conventional allopurinol, febuxostat and benzbromarone may be more effective in reducing the risk of progression to dialysis and in lowering SUA levels in CKD populations.

BACKGROUND: This study examined the progression of chronic kidney disease (CKD) by using average annual decline in estimated GFR (eGFR) and its risk factors in a 10-year follow-up CKD cohort. METHODS: A prospective, observational cohort study, 4600 individuals fulfilled the definition of CKD, with or without proteinuria, were followed for 10 years. The eGFR was estimated by the MDRD equation. Linear regression was used to estimate participants' annual decline rate in eGFR. We defined subjects with annual eGFR decline rate <1 ml/min/1.73 m2 as non-progression and the decline rate over 3 ml/min/1.73 m2 as rapid progression. RESULTS: During the follow-up period, 2870 (62.4%) individuals had annual eGFR decline rate greater than 1 ml/min/1.73 m2. The eGFR decline rate was slower in individuals with CKD diagnosed over the age of 60 years than those with onset at a younger age. Comparing to subjects with decline rate <1 ml/min/1.73 m2/year, the odds ratio (OR) of developing rapid CKD progression for diabetes, proteinuria and late onset of CKD was 1.72 (95% CI: 1.48-2.00), 1.89(1.63-2.20) and 0.68 (0.56-0.81), respectively. When the model was adjusted for the latest CKD stage, comparing to those with CKD stage 1, patients with stage 4 and stage 5 have significantly higher risks for rapid progression (OR, 5.17 (2.60-10.25), 19.83 (10.05-39.10), respectively). However, such risk was not observed among patients with the latest CKD stage 2 and 3. The risk for incident ESRD was 17% higher for each 1 ml/min/1.73 m2 increasing in annual decline rate. CONCLUSIONS: Not everyone with CKD develops ESRD after a 10-year follow-up. Absolute annual eGFR decline rate can help clinicians to better predict the progression of CKD. Individuals with renal function decline rate over 3 ml/min/1.73 m2/year require intensive CKD care.