Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
J Pharm Sci. 2011 Sep;100(9):3696-707. doi: 10.1002/jps.22641. Epub 2011 Jun 7.
Uremic toxins accumulate in patients with chronic kidney diseases (CKDs) and cause further progression of renal damage and cardiovascular diseases. Recently, it was reported that some of the organic anion transporting polypeptides (OATPs) and the organic anion transporters (OATs) are involved in the renal elimination of uremic toxins. SLCO4C1 is the only OATP expressed at the basolateral side of proximal tubular cells in human kidney, and it mediates the excretion of uremic toxins. The overexpression of human SLCO4C1 in rat kidney promotes the renal excretion of uremic toxins and reduces hypertension, cardiomegaly, and renal inflammation in renal failure. Statins induce SLCO4C1 expression thorough transcriptional factor Aryl hydrocarbon receptor through binding of the xenobiotic responsive element at its promoter region. The administration of statin in a rat renal failure model facilitated the elimination of uremic toxins and mitigated organ damage. In addition, metabolomic analysis of rat renal failure models and patients with CKD by capillary electrophoresis-mass spectrometry is a useful method for identifying new uremic solutes and explores surrogate biomarkers for detecting the progression of early stage CKD.
尿毒症毒素在慢性肾脏病（CKD）患者体内蓄积，导致肾脏损害和心血管疾病进一步加重。最近有报道称，一些有机阴离子转运多肽（OATPs）和有机阴离子转运体（OATs）参与尿毒症毒素的肾排泄。SLCO4C1 是人类肾脏近端肾小管细胞基底外侧唯一表达的 OATP，介导尿毒症毒素的排泄。人 SLCO4C1 在大鼠肾脏中的过表达促进了尿毒症毒素的肾排泄，减轻了肾衰竭引起的高血压、心脏肥大和肾脏炎症。他汀类药物通过结合其启动子区域的外源响应元件，通过转录因子芳香烃受体诱导 SLCO4C1 表达。在肾衰竭大鼠模型中给予他汀类药物可促进尿毒症毒素的清除，并减轻器官损伤。此外，通过毛细管电泳-质谱对大鼠肾衰竭模型和 CKD 患者进行代谢组学分析是一种识别新尿毒症溶质和探索用于检测早期 CKD 进展的替代生物标志物的有用方法。
