Decreased extra-renal urate excretion is a common cause of hyperuricemia.
Decreased extra-renal urate excretion is a common cause of hyperuricemia.
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DOI：
10.1038/ncomms1756
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发表时间：
2012-04-03
影响因子：
16.6
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中科院分区：
文献类型：
--
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ABCG2，也被称为BCRP，是一种高容量尿酸盐输出物，其功能障碍会增加痛风/高尿酸血症的风险。一般来说，高尿酸血症仅根据肾脏尿酸盐排泄情况分为尿酸盐“生产过剩类型”和/或“排泄不足类型”，没有考虑肾外途径。在这里，我们表明ABCG2功能障碍导致的肾外尿酸排泄减少是高尿酸血症的常见机制。对644例门诊男性高尿酸血症患者进行尿尿酸排泄量等临床参数检测。矛盾的是，ABCG2出口功能障碍显著增加了尿尿酸盐排泄和尿酸盐过剩的风险比。ABCG2基因敲除的小鼠表现出血清尿酸水平和肾尿酸排泄增加，而肠道尿酸排泄减少。再加上ABCG2在肾外组织中的高表达，我们的数据表明，目前高尿酸血症概念中的“生产过剩类型”应更名为“肾超负荷型”，它包括两个亚型--“肾外尿酸排泄不足”和真正的“尿酸盐分泌过剩”--为治疗高尿酸血症和痛风提供了一个新的概念。高尿酸血症，或痛风，被认为是由于尿酸盐产量过高或肾脏尿酸盐排泄减少引起的。Ichida等人。说明尿酸盐的肾外排泄在高尿酸血症的发病机制中也有一定的作用，并提出了高尿酸血症患者的新分类。
ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2-knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes—'extra-renal urate underexcretion' and genuine 'urate overproduction'—providing a new concept valuable for the treatment of hyperuricemia and gout. Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichida et al. show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.
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