Development of bio-artificial kidney

生物人工肾的研制

• 批准号: 16591270
• 负责人: FUJIMURA Akio
• 金额: $ 1.98万
• 依托单位: JICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591270/
• 关键词: chronic renal failure; blood purification; organic anion transporter-3; indoxylsulfate; uremic toxin; arteriosclerosis; 尿素症性物質; 血管平滑筋; 有機アニオン輸送体; ABCA8

Anionic middle molecule uremic toxins, which can not be removed by conventional hemodialysis, play major role for progress of arteriosclerosis in patients with chronic renal failure. Most of the toxins, such as indoxyl sulfate, is secreted via organic anion transporter-3 (OAT-3) in proximal tubule cells in healthy subjects. To develop a novel hybrid artificial kidney, where the proximal tubular cells over-expressing OAT-3 are cultured on hollow fibers, we performed following experiments.1) We established cultured proximal tubule cells over-expressing OAT-3. We confirmed higher transport of indoxyl sulfate in the cells and also higher expression of the protein by Western blot and immuno-histochemistry.2) We succeeded to seed the cells onto hollowfiber modules, which we previously reported.3) We found higher selective removal of indoxyl sulfate by the system in vitro. The clearance of indoxyl sulfate was 38 ml/min/m2, which was 8-times higher than that with control cells.4) We also applied this system to dogs with or without renal failure. We found high removal capacity of indoxyl sulfate from circulating blood of renal failure dog with a few adverse reactions.Thus, we succeeded to develop a novel hybrid artificial kidney with proximal tubular cells over-expressing OAT-3. This system may be useful to remove uremic toxins which can not be removed by conventional hemodialysis.

阴离子中分子尿毒症毒素无法通过常规血液透析清除，对慢性肾功能衰竭患者动脉硬化的进展起着重要作用。大多数毒素，例如硫酸吲哚酚，是通过健康受试者近曲小管细胞中的有机阴离子转运蛋白 3 (OAT-3) 分泌的。为了开发一种新型混合人工肾，其中在中空纤维上培养过表达 OAT-3 的近端肾小管细胞，我们进行了以下实验。1）我们建立了培养的过表达 OAT-3 的近端肾小管细胞。我们通过蛋白质印迹和免疫组织化学证实了硫酸吲哚酚在细胞中的更高转运以及该蛋白质的更高表达。2）我们成功地将细胞接种到我们之前报道过的中空纤维模块上。3）我们发现更高的选择性去除硫酸吲哚酚由体外制得。硫酸吲哚酚的清除率为38ml/min/m2，比对照细胞高8倍。4)我们还将该系统应用于有或没有肾衰竭的狗。我们发现肾衰竭犬循环血中硫酸吲哚酚的清除能力较高，且不良反应较少。因此，我们成功开发了一种近端肾小管细胞过表达OAT-3的新型混合人工肾。该系统可用于去除传统血液透析无法去除的尿毒症毒素。

项目成果

Adsorption of oxacalcitriol by polysulfone haemodialyzer in patients with secondary hyperparathyroidism.

继发性甲状旁腺功能亢进症患者聚砜血液透析器对奥沙骨化三醇的吸附。

• 发表时间: 2004
• 期刊: Br J Clin Pharmacol 58
• 作者: Tsuruoka S;Fujimura A (6番目) et al.
• 通讯作者: Fujimura A (6番目) et al.

β2-microglobulin adsorption column reduces digoxin trough level during hemodialysis : 3 case reports.

β2-微球蛋白吸附柱降低血液透析期间地高辛谷浓度：3 例报告。

• 发表时间: 2004
• 期刊: Ther.Drug Monit 26
• 作者: Tsuruoka S;et al.
• 通讯作者: et al.

A double-compartment cell culture apparatus : its construction and biochemical evaluation for bioartificial liver support system.

双室细胞培养装置：生物人工肝支持系统的构建和生化评价。

• 发表时间: 2006
• 期刊: Cell Transplant 15(10)
• 作者: Takahashi M;Tsuruoka S;et al.
• 通讯作者: et al.

細胞生物学講座 : ハイブリッド型人工腎臓。

细胞生物学课程：混合人工肾。

• 发表时间: 2004
• 期刊: 細胞 36(13)
• 作者: 鶴岡秀一;他
• 通讯作者: 他

Cyclosporin produces distal Renal Tubular Acidosis by blocking peptidyl cis-trans prolyl isomerase activity of cyclophilin.

环孢菌素通过阻断亲环蛋白的肽基顺反脯氨酰异构酶活性而产生远端肾小管酸中毒。

• 发表时间: 2005
• 期刊: Am J Physiol Renal Physiol 288(1)
• 作者: Watanabe S;Tsuruoka S;et al.
• 通讯作者: et al.