Fractional clearance of urate: validation of measurement in spot-urine samples in healthy subjects and gouty patients

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

Rational pharmacotherapy (RPT) in goutology: Define the serum uric acid target & treat-to-target patient cohort and review on urate lowering therapy (ULT) applying synthetic drugs

“…2. Generally in gout patients the FCU is slightly diminished when compared with controls [16]. The Simkin Index (SI) is complex to interpret as it's value is associated with medication that is used.…”

Patients with gout differ from healthy subjects in renal response to changes in serum uric acid

“…Hyperuricemia is caused primarily (in 80%-90% of subjects) by inefficient renal uric acid excretion, with diet and overproduction of uric acid playing a major role in approximately 10%-20% of subjects [6]. It is possible for individuals to have both components of overproduction and inefficient renal excretion of uric acid mediating their disease [7].…”

Hyperuricaemia: contributions of urate transporter ABCG2 and the fractional renal clearance of urate

“…It has been widely accepted that in otherwise well individuals with normal glomerular filtration rates, the dominant cause of hyperuricaemia is inefficient clearance of urate via the kidneys, as quantified by a low fractional (renal) clearance of urate (FCU, a.k.a. fractional excretion of uric acid—FEua; renal urate clearance/creatinine clearance) relative to those with normal urate concentrations 3. However, there is considerable overlap in the distribution of FCU between normouricaemic and hyperuricaemic people, and factors other than FCU contribute to the risk of developing hyperuricaemia.…”