Urinary organic anion transporter protein profiles in AKI
Urinary organic anion transporter protein profiles in AKI
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DOI：
10.1093/ndt/gfr541
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发表时间：
2012-04-01
影响因子：
6.1
通讯作者：
Dinour, Dganit
中科院分区：
文献类型：
--
作者：
Kunin, Margarita;Holtzman, Eli J.;Dinour, Dganit
背景。有机阴离子转运蛋白（OAT）位于近曲小管细胞的基底外侧或顶膜上，介导各种药物和内源性代谢物的吸收和分泌。研究表明，急性肾损伤（AKI）中的细胞损伤涉及三种形式的损伤：导致细胞极性丧失的亚致死损伤、通过凋亡和坏死导致的细胞死亡。我们假设 AKI 中 OAT 蛋白的细胞定位错误将改变尿液中 OAT 蛋白的分布。方法。该研究纳入了 30 名 AKI 患者。 AKI 的定义是临床病程、每日尿量、补液反应、尿沉渣、钠排泄分数 (FeNa) 和尿渗透压。通过对 AKI 患者和对照受试者的尿膜部分样本（外泌体）进行半定量免疫印迹测量尿液中 OAT1、OAT3 和 OAT4 蛋白丰度。结果。尽管根据血清肌酐测量，所有研究的患者都达到了相似的肾衰竭严重程度，但其中一些患者仅通过支持性护理即可从 AKI 中恢复，而另一些患者则需要肾脏替代治疗 (RRT)。 OAT1 和 OAT3 通常位于近曲小管细胞的基底外侧膜中，在对照受试者的尿液中检测到水平较低，并且在所有 AKI 患者中显着增加。 OAT4 蛋白通常位于近曲小管细胞的管腔膜中，但在对照受试者的尿液中却大量存在。有趣的是，在最终康复的 AKI 患者中，尿中 OAT4 显着低于对照组，而在需要 RRT 的患者中，则高于对照组。结论。我们已经证明 OAT 在 AKI 中的作用是错误的。尿 OAT 蛋白谱可以帮助我们了解该疾病的病理生理学，并且可能是 AKI 严重程度的标志。早期可逆性近端肾小管损伤的 AKI 患者尿中 OAT1 和 OAT3 较高，OAT4 较低，而严重 AKI 患者尿中 OAT1、OAT3 和 OAT4 较高。
Background. Organic anion transporters (OATs) are located on either the basolateral or the apical membrane of the proximal tubule cell and mediate the absorption and secretion of various drugs and endogenous metabolites. It has been shown that cellular damage in acute kidney injury (AKI) involves three forms of injury: sublethal damage resulting in loss of cell polarity, cell death through apoptosis and necrosis. We hypothesize that cellular mistargeting of OAT proteins in AKI will change the profile of OAT proteins in urine.Methods. Thirty AKI patients were included in the study. AKI was defined by clinical course, daily urine output, response to fluid repletion, urinary sediment, fractional excretion of sodium (FeNa) and urine osmolality. Urinary OAT1, OAT3 and OAT4 protein abundance was measured from semiquantitative immunoblots of urine membrane fraction samples (exosome) collected from patients with AKI and from control subjects.Results. Although all patients studied reached a similar severity of renal failure measured by serum creatinine, some of them recovered from AKI with supportive care only, while others required renal replacement therapy (RRT). OAT1 and OAT3, which are normally localized in the basolateral membrane of the proximal tubule cell, were detected at low levels in urine from control subjects and were increased significantly in all patients with AKI. OAT4 protein, which is normally localized in the luminal membrane of proximal tubule cells, was present in abundance in urine of control subjects. Interestingly, in patients with AKI who eventually recovered, urinary OAT4 was found to be significantly lower than in controls, while in patients who needed RRT, it was higher than in controls.Conclusions. We have shown that OATs are mistargeted in AKI. The urinary OAT protein profile can help us to learn about the pathophysiology of the disease and might be a marker of AKI severity. AKI patients with early reversible proximal tubular damage will have high urine OAT1 and OAT3 and low OAT4, while patients with severe AKI will have high urine OAT1, OAT3 and OAT4.