Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachiouji, Tokyo 192-0392, Japan.
Nat Commun. 2012 Apr 3;3:764. doi: 10.1038/ncomms1756.
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.
ABCG2，也称为 BCRP，是一种高容量的尿酸外排蛋白，其功能障碍会增加痛风/高尿酸血症的风险。通常，高尿酸血症仅根据肾脏尿酸排泄被分为尿酸“产生过多型”和/或“排泄不足型”，而不考虑肾脏外途径。在这里，我们表明 ABCG2 功能障碍导致的肾脏外尿酸排泄减少是高尿酸血症的常见机制。在 644 名男性高尿酸血症门诊患者中检查了临床参数，包括尿尿酸排泄。矛盾的是，ABCG2 外排功能障碍显著增加了尿尿酸排泄和尿酸产生过多的风险比。Abcg2 敲除小鼠表现出血清尿酸水平升高和肾脏尿酸排泄增加，以及肠道尿酸排泄减少。结合肾脏外组织中高 ABCG2 表达，我们的数据表明，当前高尿酸血症概念中的“产生过多型”应更名为“肾脏过载型”，其包括两个亚型——“肾脏外尿酸排泄不足”和真正的“尿酸产生过多”——为高尿酸血症和痛风的治疗提供了一个有价值的新概念。
