Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial.
OBJECTIVE
Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders.


METHODS
Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest.


RESULTS
Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02).


CONCLUSIONS
In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.
Garg
Jay P
JP
Department of Medicine Research, University of California-San Francisco, UCSF Laurel Heights Suite 430, 3333 California Street, San Francisco, CA 94118-1211, USA.
Chasan-Taber
Scott
S
Blair
Andrew
A
Plone
Melissa
M
Bommer
Juergen
J
Raggi
Paolo
P
Chertow
Glenn M
GM
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002118:Calcium; D004852:Epoxy Compounds / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009994:Osmolar Concentration; D028044:Phosphate-Binding Proteins / Q000737:chemistry / Q000627:therapeutic use*; D011073:Polyamines; D011095:Polyethylenes / Q000627:therapeutic use*; D006435:Renal Dialysis; D000069603:Sevelamer; D014527:Uric Acid / Q000037:antagonists & inhibitors / Q000097:blood*
D015415:Biomarkers; D004852:Epoxy Compounds; D028044:Phosphate-Binding Proteins; D011073:Polyamines; D011095:Polyethylenes; D014527:Uric Acid; D000069603:Sevelamer; D002118:Calcium