Taniguchi Atsuo, Kamatani Naoyuki
Institute of Rneumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
Curr Opin Rheumatol. 2008 Mar;20(2):192-7. doi: 10.1097/BOR.0b013e3282f33f87.
Impaired renal uric acid excretion is the major mechanism of hyperuricemia in patients with primary gout. This review highlights recent advances in the knowledge of normal mechanisms of renal uric acid handling and derangement of these mechanisms in uric acid underexcretion.
The discovery of URAT1 has facilitated identification of other molecules potentially involved in uric acid transport in the renal tubules. Some of these molecules show gender differential expression in animal experiments. Sodium-dependent monocarboxylate cotransporters have been shown to transport lactate and butyrate, and may have roles in hyperuricemia associated with diabetic ketoacidosis and alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the development of hyperuricemia or gout, although confirmation is needed. Mechanisms of hyperuricemia associated with uric acid underexcretion in patients with familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal tubular salt wasting and compensatory upregulation of the resorption of sodium and uric acid in the proximal tubule may explain the hyperuricemia associated with this disorder.
Much progress has been made in understanding the mechanisms of renal uric acid handling. Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.
肾脏尿酸排泄受损是原发性痛风患者高尿酸血症的主要机制。本综述重点介绍了肾脏尿酸处理正常机制以及尿酸排泄减少时这些机制紊乱方面的最新研究进展。
URAT1的发现有助于识别肾小管中其他可能参与尿酸转运的分子。其中一些分子在动物实验中表现出性别差异表达。钠依赖性单羧酸共转运体已被证明可转运乳酸和丁酸，可能在与糖尿病酮症酸中毒和酒精摄入相关的高尿酸血症中起作用。SLC22A12中的某些多态性可能与高尿酸血症或痛风的发生有关，尽管仍需证实。家族性青少年高尿酸血症肾病患者中与尿酸排泄减少相关的高尿酸血症机制也有待阐明。远端肾小管盐耗竭以及近端肾小管钠和尿酸重吸收的代偿性上调可能解释了与该疾病相关的高尿酸血症。
在理解肾脏尿酸处理机制方面已取得很大进展。阐明家族性青少年高尿酸血症肾病患者高尿酸血症的机制将有助于了解尿调节蛋白的功能，其功能受损最终导致尿酸排泄减少。
