Kannangara Diluk R W, Ramasamy Sheena N, Indraratna Praveen L, Stocker Sophie L, Graham Garry G, Jones Graham, Portek Ian, Williams Kenneth M, Day Richard O
Arthritis Res Ther. 2012 Aug 17;14(4):R189. doi: 10.1186/ar4020.
Hyperuricemia 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.
Timed (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.
No 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).
The 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.
ACTRN12611000743965.
高尿酸血症是痛风的最大危险因素,由尿酸生成过多和/或肾脏对尿酸清除效率低下所致。尿酸的肾脏清除分数(FCU,尿酸清除率/肌酐清除率)已被提议作为一种工具,用于识别尿酸清除效率低下的个体。本研究的目的是验证使用随机尿样测量FCU作为评估肾脏清除尿酸效率的可靠指标,并探讨其在健康受试者和痛风患者中的分布情况。
采用定时(随机、2小时、4小时、6小时、12小时和24小时)尿液收集法,在12名健康受试者中得出FCU。然后,在13名健康受试者中,每天两次测定随机尿样的FCU,在3个非连续日重复进行。在11名健康受试者中探讨了别嘌醇、丙磺舒及其联合用药对FCU的影响。对36例接受别嘌醇治疗的痛风患者测定FCU。检测118名健康受试者的FCU分布,并与36例痛风患者的FCU分布进行比较。
随机尿样和24小时尿样得出的FCU之间未观察到实质性或统计学上的显著差异。变异系数(CV)均为28%。随机FCU在日内或日间均未出现显著变化,受试者内平均CV为16.4%。丙磺舒使FCU升高(P<0.05),而别嘌醇在健康或痛风受试者中均未改变FCU。痛风患者的FCU低于健康受试者(4.8%对6.9%;P<0.0001)。
本研究表明,随机FCU是评估肾脏从血液进而从组织中清除尿酸效率的一种方便、有效且可靠的指标。随机FCU测定可能为研究肾脏从血液中清除尿酸的不同效率背后的分子机制提供有用的关联信息。
ACTRN12611000743965。