血液透析用從透析液供應鐵劑之調製方法

Method for Iron Delivery from Dialysate in Hemodialysis

葉日兆(Jih-Chao Yeh)

指導教授 ： 張炎林

中原大學/工學院/醫學工程研究所/碩士(2006年)

https://doi.org/10.6840/cycu200600484

摘要

接受血液透析治療的末期腎病患者的貧血改善，目前皆使用紅血球生成素，但是需要補充鐵劑方能畢其功。洗腎患者口服投予鐵劑的方式，已證實會產生不順應性與腸胃道副作用，而且有時不能如預期提升血球比容與血紅素濃度。另外，以靜脈注射葡聚醣鐵、蔗糖酸鐵或葡萄糖酸鐵等鐵劑已有多年歷史，也是目前最常使用的投予方式，在臨床上已證實偶而伴有嚴重副作用包括低血壓與不能引發抗體的過敏反應。所以，不論以口服或是靜脈投予鐵劑皆有風險及副作用。三價鐵離子可以強烈與焦磷酸結合形成複合物；焦磷酸是體內觸動鐵質離開轉鐵蛋白，使鐵質在轉鐵蛋白分子之間進行鐵的轉移交換；鐵焦磷酸鹽分子量745.2道爾頓，可溶於水且可穿過透析器薄膜，這些性質強烈顯示鐵焦磷酸鹽適合添加在透析液中，對於長期洗腎患者，透析治療時鐵劑可經由透析液穿過透析薄膜進入血液以補充患者體內鐵質。因此，本研究從透析液補充鐵劑(鐵焦磷酸鹽)成為新的嘗試方式。研究包括1.含預定FePyP含量之透析液的調製方式；2.FePyP在重碳酸鹽濃縮液，典型透析液與酸性濃縮液中的溶解度試驗；3.模擬臨床血液透析的體外回流系統試驗；4.含FrPyP透析液的氧化壓力評估。將鐵焦磷酸鹽分別加入NaHCO3濃縮液及典型透析液中，以TEXTRON U-240 PLUS檢測溶液鐵質濃度，在37℃下，得到在NaHCO3濃縮液中鐵劑的最大溶解度為6.96 mg/dl及在透析液中為4.29mg/dl。在體外回流實驗中，將37℃豬血漿1.0 liter回流透析，典型透析液含Fe 15ug /dl,透析器採用Fresenius HdF100S，血漿流量300 ml/min，透析液流量500 ml/min，透析2小時。過程中檢驗血漿鐵與轉鐵蛋白飽和度，並檢測氧化壓力。結果顯示，Fe的傳送速率平均為23.84 ug/dl，而且沒有明顯的氧化壓力上升情形。本體外研究證明經過適當調製FePyP透析液，鐵劑可以有效經由透析器傳送到血漿中，並與轉鐵蛋白結合，而且無氧化壓力的影響；初步證明含FePyP透析液在血流透析改善臨床上同樣補充鐵劑的可行性。

關鍵字

氧化壓力 ； 質傳模式 ； 血液透析 ； 透析液 ； 鐵焦磷酸鹽

並列摘要

Anemia of chronic renal failure is primary caused by a relative deficiency of erythropoietin. Erythropoientin therapy rapidly leads to iron deficiency and needs oral or intravenous iron supplement to maintain optimal iron balance. Oral iron supplements have failed primarily because of noncompliance in addition to gastrointestinal advance effect. Oral iron supplements shows no hematologic benefit over on iron therapy or over placebo in hemodialysis patients. As an alternative to the oral route, iron has been administered intravenously for more than 100 years. The colloidal iron compounds currently used for intravenous administration such as iron dextran, iron saccharate , or iron gluconate are also associated with serious side-effect, including hypotension and anaphylactoid reaction. However, neither the oral nor intravenous iron therapy route is ideal and have risks and disadvantages. Ferric iron is strongly completed by pyrophosphate; pyrophosphate is known to trigger iron removal from transferring enhance iron transfer from transferring to ferritin, and promote iron exchange between transferring molecules; ferric pyrophosphate(MW of 745.2D) is soluble in water and permeable through dialyzer membrane; these properties suggest that ferric pyrophosphate may be suitable for parenteral administration via dialysate. In this study, a new method was developed for iron administration via dialysate to maintain hemodialysis patients. The study includes the following: (1) the methods of preparing the bicarbonate concentrates with a defined iron concentration achieved by addition of FePyP; (2) in vitro studies on the solubilities of FePyP in bicarbonate concentrate, typical dialysate and acid concentrate; (3) in vitro recycle system to simulate extracorporeal hemodialysis as a signal pool model; and (4) oxidative effect of FePyP during the recycle experiment.
We added ferric pyrophosphate in NaHCO3 concentrate and dialysate. The concentration of each sample was tested using Beckman array protein system. At 37℃, the maximum solubility was 6.96 mg/dl in NaHCO3 concentrate, and 4.29 mg/dl in dialysate. In addition, a series of theoretical equatons were proposed. In the in vitro recycle study, a volume of 1.0 liter porcine plasma at 37℃ was dialyzed against dialysate with 15 ug/dl of Fe for two hours. A Fresenius HdF 100s dialyzer was used at a plasma flow rate of 300 ml/min and dialysate flow rate of 500 ml/min. The increasement in serum iron and transferring saturation was measured. The oxidative stress was also detected.
A Fe transfer rate of 23.84 ug/min was achieved and no significant oxidative effect of FePyP in plasma was observed. It is demonstrated that the FePyP is soluble in hemodialysis solutions in adequate concentrations, efficiently transfers from the dialysate to the blood compartment, and binds to the transferrin in the plasma.

並列關鍵字

Hemodialysis ； Ferric pyrophosphate ； Anemia ； Dialysate ； Oxidative stress ； Mass transfer model

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