Abstract
IntroductionHyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient clearance of urate. The aim of the present studies was to validate the measurement of FCU by using spot-urine samples as a reliable indicator of the efficiency of the kidney to remove urate and to explore its distribution in healthy subjects and gouty patients.MethodsTimed (spot, 2-hour, 4-hour, 6-hour, 12-hour, and 24-hour) urine collections were used to derive FCU in 12 healthy subjects. FCUs from spot-urine samples were then determined in 13 healthy subjects twice a day, repeated on 3 nonconsecutive days. The effect of allopurinol, probenecid, and the combination on FCU was explored in 11 healthy subjects. FCU was determined in 36 patients with gout being treated with allopurinol. The distribution of FCU was examined in 118 healthy subjects and compared with that from the 36 patients with gout.ResultsNo substantive or statistically significant differences were observed between the FCUs derived from spot and 24-hour urine collections. Coefficients of variation (CVs) were both 28%. No significant variation in the spot FCU was obtained either within or between days, with mean intrasubject CV of 16.4%. FCU increased with probenecid (P < 0.05), whereas allopurinol did not change the FCU in healthy or gouty subjects. FCUs of patients with gout were lower than the FCUs of healthy subjects (4.8% versus 6.9%; P < 0.0001).ConclusionsThe present studies indicate that the spot-FCU is a convenient, valid, and reliable indicator of the efficiency of the kidney in removing urate from the blood and thus from tissues. Spot-FCU determinations may provide useful correlates in studies investigating molecular mechanisms underpinning the observed range of efficiencies of the kidneys in clearing urate from the blood.Trial RegistrationACTRN12611000743965
Highlights
Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate
It is generally believed that most hyperuricemia in subjects with normal glomerular filtration rates results from a significant inefficiency of the kidneys to clear urate [6,7]
Part 1: Validation Study 1A: Comparison of spot fractional clearance of urate (FCU) with timed FCUs over 24 hours The mean FCU collected from spot morning urine and plasma samples was similar (7.4%) to the FCUs determined from 24-hour collections (6.9%) (Table 1)
Summary
Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. Gout is the most prevalent inflammatory arthritis in men, and its incidence is increasing globally [1] It is caused by deposition of monosodium urate monohydrate (MSU) crystals in and around joints after longstanding hyperuricemia. Overproduction of urate, as a result of high dietary intake of urate precursors or abnormal enzymatic synthesis, accounts for hyperuricemia in approximately 10% of patients [4]. It is generally believed that most hyperuricemia in subjects with normal glomerular filtration rates results from a significant inefficiency of the kidneys to clear urate [6,7]. The inefficiency of renal clearance in those with normal glomerular filtration rates is considered likely to be the result of impaired tubular secretion, increased tubular resorption, or a combination of both
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