Urate-lowering Therapy In Patients Research Articles

Management of asymptomatic hyperuricaemia in patients with chronic kidney disease by Japanese nephrologists: A questionnaire survey

Hyperuricaemia is associated with chronic kidney disease (CKD) progression and cardiovascular events (CVE). In a US study, only 4% of rheumatologists initiated urate-lowering therapy in patients with asymptomatic hyperuricaemia (AHU). The present study aimed to clarify how Japanese board-certified nephrologists manage AHU in CKD patients. Questionnaires on management of AHU in CKD stage 3 or more were mailed to 1500 Japanese board-certified nephrologists, excluding paediatricians and urologists, randomly selected from the directory of the Japanese Society of Nephrology (n = 2976). Five hundred and ninety-five nephrologists (40%) responded. Most nephrologists (84-89%) recommended that AHU in patients in CKD stages 3-5 should be treated, but fewer nephrologists (63%) recommended that AHU in patients of CKD stage 5D should be treated. The serum urate level to start urate-lowering therapy and the target serum urate level to be achieved (mg/dL) were 8.2 ± 0.9 and 6.9 ± 0.9, 8.4 ± 0.9 and 7.0 ± 1.0, 8.6 ± 1.0 and 7.3 ± 1.1, and 9.1 ± 1.2 and 7.8 ± 1.3 at stages 3, 4, 5 and 5D, respectively. The most frequently used maximal dosage of allopurinol was 100 mg/day at each stage. Benzbromarone was used in 52% of patients at stage 3, but only in 29%, 13% and 5% of patients at stages 4, 5 and 5D, respectively. The most important reasons to treat AHU at CKD stages 3-5 were prevention of CKD progression (45%), CVE (33%), gout (18%) and urolithiasis (3%). Most Japanese nephrologists treat AHU in pre-dialysis CKD with an aim to prevent CKD progression or CVE mainly by allopurinol.

Febuxostat in Gout: Serum Urate Response in Uric Acid Overproducers and Underexcretors

Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors. Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28. Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers. Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.