- 期刊
以動力學模式之定量化透析策略應用於血液透析治療
Quantitative Controlling Strategies for Kinetic Models of Hemodialysis Therapy
摘要
Beta-2-microglobulin(β2-M)被認爲可作爲中分子量蛋白質毒素之代表，累積在慢性患者體內，逐漸聚合形成澱粉樣蛋白，引起澱粉樣變性病。但是由於β2-M的聚合反應的動力學機轉仍然未明，臨床上至今亦未能訂出透析治療時的適當透析劑量。因此本文根據文獻資料，提出較完整的動力學模式，進行理論模擬與臨床實驗評估。首先藉此模式針對慢性腎衰竭病人個體的差異性與臨床透析操作條件的不同，討論病人參數（間質液與血漿間之質傳速率係數Kc、透析前血漿濃度Cp1、透析前體重BW1、非透析期間新陳代謝產生速率Gc）及透析操作參數（超過濾速率Qf與透析器出清率CL）對定量化透析的影響。接著藉此模式進行臨床實驗評估，依據八位慢性腎衰竭病人的臨床資料，探討不同透析膜材除去β2-M的性能，結果顯示PS與PMMA透析膜材分別可使血漿中β2-M之濃度在透析結束後降低42.6±6.3%與40.0±8.9%。此外，根據PMMA透析膜材治療病人的臨床數據，求算出病人在透析期間免疫系統刺激產生速率(Gi)，其值大約介於0.03~0.16mg/min，由此Gi值可瞭解透析膜材對病人免疫系統補體活化程度，進一步評估透析膜材的生物適應性。最後自透析治療實例中求取病人體內間質液與血漿的質傳速率係數(Kc)，其值大約介於100~300ml/min，此參數配合動力學模式未來可用於分析與模擬病人血漿中β2-M濃度長時間的變化。希望透過本動力學模式的建立與分析，提供醫療人員在臨床上決定病人治療處方的參考，將來有助於指引臨床透析治療，以訂出β2-M適當透析劑量，提高治療品質。
並列摘要
Beta-2-microglobulin (β2-M) is recognized as a major medium-molecular-weight protein toxin in patients experiencing chronic renal failure. The toxicity of β2-M results from polymerization of an intact molecule to form amyloids, the accumulation of which causes amyloidosis. Currently, the mechanism of β2-M polymerization is unknown; therefore, an adequate clinical method for removal of β2-M has yet to be discovered. In this study, a tentative kinetic model of β2-M polymerization for theoretical simulation and clinical evaluation is proposed. Due to individual differences between patients and dialysis conditions, patient-specific parameters (vascular mass-transfer coefficient, predialytic plasma concentration, predialytic body weight, and cellular catabolism production rate) and the parameters for quantitatively controlling dialysis (ultrafiltration rate and dialyzer clearance) were measured for comparison. The clinical data used in the study were obtained from eight stable end-stage renally diseased patients. The results were used to investigate the effects of a dialysis membrane on β2-M removal. The results also indicated that treatment with Polysulfone (PS) and Polymethylmethacrylate (PMMA) reduced the plasma concentration of β2-M to 42.6 ± 6.3% and 40.0 ± 8.9%, respectively. Kinetic simulation of PMMA treatment yielded immunological response rates (Gi) between 0.03 and 0.16 mg/min, thereby suggesting that the Gi value may be considered a useful indicator of membrane biocompatibility. Moreover, the vascular mass-transfer coefficients of individual patients were determined from the clinical data. The kinetic model of β2-M polymerization proposed in this study may be a valuable guide for developing an effective dialysis method for the removal of β2-M. Furthermore, the clinical results obtained and the analyses thereof may be useful for developing future therapies for treating renal failure.