Effect of fenofibrate on uric acid metabolism and urate transporter 1.

OBJECTIVE: To examine the effects of fenofibrate, an antilipotropic drug, on uric acid metabolism in healthy male subjects and on urate transporter 1 (URAT1). METHODS: Fenofibrate was administered to nine male volunteers at a dose of 300 mg (corresponding to 200 mg of micronized fenofibrate), and the metabolic parameters of uric acid were investigated for more than 12 hours. In addition, the effect of fenofibrate on URAT1-expressing cells was examined. RESULTS: After the administration of fenofibrate, the concentration of serum uric acid had significantly decreased from 5.8+/-0.4 mg/dL to 4.3+/-0.3 mg/dL at 10 h. Uric acid clearance and the fractional excretion of uric acid increased. Fenofibric acid, a fenofibrate metabolite, inhibited URAT1 to an extent similar to that observed with benzbromarone and losartan. CONCLUSION: Fenofibrate decreased serum uric acid levels by increasing its urinary excretion, most likely through the inhibition of URAT1 by fenofibric acid, its major metabolite.

Sevelamer decreases serum uric acid concentration through adsorption of uric acid in maintenance hemodialysis patients.

BACKGROUND: Sevelamer, a nonabsorbed hydrogel that binds phosphate, is reported to reduce the serum urate concentration in maintenance hemodialysis patients, however the urate-lowering mechanism remains obscure. In this study we verify the urate-lowering effect of sevelamer in Japan in which the hemodialysis environment is different from that of western countries, and we also clarify the urate-lowering mechanism of sevelamer. METHODS: A total of 127 Japanese patients undergoing maintenance hemodialysis were investigated. These patients consisted of 93 males and 34 females, and their mean age was 58.4+/-12.4 years (range, 25-88 years). The mean duration of hemodialysis was 8.7+/-6.1 years (range, 0.5-27.5 years). Sevelamer was added to each patient's former prescription for the treatment of hyperphosphatemia, and the changes in laboratory data before and after administration of sevelamer were compared. In order to clarify the mechanism of urate-lowering effect by sevelamer, a urate adsorption experiment was carried out in vitro. RESULTS: Sevelamer significantly decreased serum phosphate value three and six months after administration. Sevelamer showed a significant reduction in serum urate values in maintenance hemodialysis patients with hyperuricemia, but not in patients with normouricemia. The change rate of serum urate correlated with the change rate of serum phosphate and the change rate of serum calcium x phosphate product, but did not correlate with that of serum calcium. Sevelamer hydrochloride adsorbed urate in vitro. CONCLUSION: Sevelamer decreases serum urate possibly by adsorbing urate in hemodialysis patients.

[Usefulness of combination treatment using allopurinol and benzbromarone for gout and hyperuricemia accompanying renal dysfunction: kinetic analysis of oxypurinol].

A study was conducted to determine whether combination treatment using allopurinol and benzbromarone was more useful than single allopurinol treatment for the gout and hyperuricemia accompanying renal dysfunction. The subjects were 45 male patients who received urate-lowering treatment and showed a stable serum urate level. The patients were divided into four groups according to the urate-lowering treatment and creatinine clearance (Ccr) (A group: single treatment, normofunction, B group: single treatment, hypofunction, C group: combined treatment, normofunction, D group: combined treatment, hypofunction). There were no differences in serum urate levels among the four groups. Urate clearance (CUA)and daily urinary urate excretion (UUAV) showed significantly high values in the C group, but no difference was seen in the fractional excretion of urate (FEUA) among the four groups. The dosage of allopurinol in the D group was significantly lower than in the A and B groups. Serum oxypurinol concentration in the C group was lower than that in the B group. Oxypurinol clearance (C oxypurinol) in the C group was significantly high compared with the B and D groups. There was a close correlation between C oxypurinol, Ccr, and CUA, with an especially strong correlation between C oxypurinol and CUA. There were no differences in the serum concentration and clearance of xanthine and hypoxanthine among the four groups. Results of the study suggested that combination treatment using allopurinol and benzbromarone for the gout and hyperuricemia accompanying renal dysfunction is more useful, because a lower dose of allopurinol can be used and the serum oxypurinol concentration is reduced compared with single allopurinol treatment.

Frequency of gouty arthritis in patients with end-stage renal disease in Japan.

OBJECTIVE: The purpose of this study was to investigate gouty arthritis in Japanese patients with end-stage renal disease (ESRD). METHODS: Questionnaires plus patient interviews and reviews of medical records were used to investigate gouty arthritis in 493 Japanese patients with ESRD receiving maintenance dialysis. RESULTS: The frequency of gouty arthritis was 4.1% for female patients and 15.4% for male patients greater than 2 years before the start of dialysis, and 0.6% for female patients and 7.7% for male patients less than 2 years before the start of dialysis. After the start of dialysis the frequency was 3.4% for the first 2 years and 1.2% thereafter in male patients, but no gouty arthritis appeared in female patients. Although the annual number of gouty attacks was 2.0+/-4.2 greater than 2 years before the start of dialysis, and 1.9+/-6.6 less than 2 years before the start of dialysis, the annual number of attacks decreased significantly after the start of dialysis to 0.2+/-0.7 in the first 2 years and 0.1+/-0.6 thereafter. CONCLUSIONS: The frequency of gouty arthritis in Japanese patients with ESRD is similar to that of patients with hyperuricemia in the general population and it is decreased slightly before dialysis; however, the frequency decreases markedly after dialysis.

[Molecular mechanism of vascular calcification in renal failure].

Vascular calcification is the most frequent cause of death in chronic renal failure. In recent studies molecular mechanism for regulation of vascular calcification is becoming to clear. An important regulator of vascular calcification is the extracellular levels of inorganic phosphate. Also, various bone matrix proteins and factors regulates vascular calcification in ESRD patients.