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Abstract
Background Serum uric Acid (sUA) concentration is a function of uric acid production and both renal and extra-renal clearance. Decreased renal clearance is well understood as a contributing factor in gout. Extra-renal clearance, however, has not been as well characterized. Estimating extra-renal clearance would allow the classification of patients with gout as having high or low extra-renal clearance. Additionally, since production must equal the sum of urinary excretion and extra-renal elimination, determining the amount of extra-renal elimination would allow estimation of the rate of uric acid production. With this information, subjects could be characterized by all three parameters that determine sUA levels.
Objectives To estimate the extra-renal uric acid clearance of patients with gout.
Methods sUA and 24-hour urinary uric acid excretion (24hrUUE) were measured in 30 patients with gout in the absence and presence of a specific URAT1 inhibitor that lowers uric acid by increasing renal uric acid excretion. In these patients, at least a 1 mg/dl decrease in sUA was achieved with the URAT1 inhibitor at steady state. Extra-renal clearance was calculated by dividing the drug-induced increase in 24hrUUE by the drug-induced decrease in sUA and adjusting units to yield ml/min. This calculation was performed twice for each patient as two sets of measurements for each patient were taken. The two calculated clearance values were then averaged.
Results The average estimated extra-renal clearance of the 30 patients with gout was 4.4 ml/min. Maximum extra-renal clearance was 16 ml/min, while some patients apparently had no measurable extra-renal elimination (Figure).
Conclusions Estimated extra-renal elimination varies greatly among patients with gout. Some patients have very low estimated extra-renal clearance which likely contributes to high sUA concentration.
Acknowledgement Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca.
Disclosure of Interest D. Hyndman Employee of: Ardea Biosciences, Inc., S. Liu Employee of: Ardea Biosciences, Inc., J. Hall Employee of: Ardea Biosciences, Inc., J. Miner Employee of: Ardea Biosciences, Inc.