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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80593完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李雅珍(Ya-Jane Lee) | |
| dc.contributor.author | Syu-Yin Lin | en |
| dc.contributor.author | 林煦茵 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:10:13Z | - |
| dc.date.available | 2022-04-28 | |
| dc.date.available | 2022-11-24T03:10:13Z | - |
| dc.date.copyright | 2021-11-19 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-25 | |
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Elevated FGF23 and disordered renal mineral handling with reduced bone mineralization in chronically erythropoietin over-expressing transgenic mice. Sci Rep 9:14989, 2019. 110. Chakrabarti S, Syme HM, Elliott J. Clinicopathological variables predicting progression of azotemia in cats with chronic kidney disease. J Vet Intern Med 26:275-81, 2012. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80593 | - |
| dc.description.abstract | "研究背景 隨著慢性腎臟病的病程進展，腎臟功能逐漸惡化會導致相關併發症如貧血、礦物質代謝與骨質異常，以及心血管疾病等。目前關於尿毒毒素、紅血球生成作用以及對於鈣磷平衡的重要因子（纖維母細胞生長因子－23）三者間的交互關係，已於細胞培養實驗、實驗鼠模型以及人類醫學中被闡述。 研究目的 由於在獸醫學領域仍缺乏相關實驗，故本實驗希望能對慢性腎病貓的血漿尿毒毒素（硫酸吲哚）、紅血球生成素以及纖維母細胞生長因子－23之交互關係進行探討，以及了解這些因子是否為貓腎臟疾病預後的指標。 研究對象 由於單次血漿檢體難以取得足量可同時檢測三者，故本實驗主要分成兩大組，分別進行硫酸吲哚－紅血球生成素（IS-EPO）組與紅血球生成素－纖維母細胞生長因子－23（EPO-FGF-23）組的檢測以了解二者的個別關連性。IS-EPO組中包含8隻健康貓與26隻慢性腎病貓，而慢性腎病貓中有3隻貧血，20隻為非貧血；另外亦區分出腎病惡化組（8隻）與非腎病惡化組（7隻）。EPO-FGF-23組中則包含7隻健康貓與15隻慢性腎病貓，而慢性腎病貓中有2隻貧血，9隻為非貧血；另外亦區分出低磷組（7隻）與高磷組（6隻）；腎病惡化組（3隻）與非腎病惡化組（6隻）。 實驗方法 以高效能液相層析儀（High Performance Liquid Chromatography）之螢光檢測法檢測貓血漿中硫酸吲哚之濃度，並以貓之商業化免疫分析套組分別檢測血漿中紅血球生成素與纖維母細胞生長因子－23之濃度。 實驗結果 與控制組相比，晚期慢性腎病貓有顯著較高的血漿硫酸吲哚的濃度（p=0.026），在腎病惡化組別也有較高濃度的趨勢（p=0.054），在經接收者操作特徵曲線（ROC）分析後顯示其具有預測腎病惡化之能力（AUC 0.804, p=0.049）。貓紅血球生成素的濃度在貓腎臟疾病組相對於控制組有上升的趨勢，但整體而言於控制組、早期腎病組與晚期腎病組間與高、低磷組間均無顯著差異，且在腎病惡化組與非腎病惡化組別間亦無達到顯著差異。而關於貓血漿中纖維母細胞生長因子－23的濃度，早期腎病組相較控制組有上升的趨勢，但整體而言於控制組、早期腎病組與晚期腎病組間與高、低磷組間均無顯著差異，且在腎病惡化組與非腎病惡化組別間亦無達到顯著差異，而以回歸分析血漿紅血球生成素與纖維母細胞生長因子－23後，於本實驗並未達到具有預測腎病惡化指標的能力。 另一方面，關於這三者與貓慢性腎病貧血的交互關係，血漿硫酸吲哚濃度於貧血與非貧血組別間並無顯著差異，然其與紅血球數之間呈現顯著負相關（p=0.040），亦與血紅素濃度（p=0.056）與血容比（p=0.083）之間具有負相關之趨勢。而在貓血漿紅血球生成素濃度的比較，雖然貧血組相較於非貧血組低，然未達顯著差異，其與紅血球相關參數之間的關係中，僅發現與平均紅血球容積具有顯著負相關（p=0.017）。最後，貓血漿纖維母細胞生長因子－23之濃度於貧血與非貧血組間未具有顯著差異，其與紅血球數成顯著正相關（Spearman: p=0.016, Linear: p=0.022），與平均紅血球容積具有顯著負相關（Spearman: p=0.011, Linear: p=0.004）。至於以這三者分別進行回歸分析預測貧血的發生之後，三者均未達到具有預測貓慢性腎病貧血的能力。 最後，關於慢性腎病貓此三者之間的相關性，本實驗結果顯示貓血漿硫酸吲哚與紅血球生成素濃度間並沒有顯著關聯性，然而在血漿紅血球生成素濃度與纖維母細胞生長因子－23之間則互相具有顯著正相關性（p=0.014）。 實驗結果與主要發現 本實驗為第一個使用專門偵測貓血漿紅血球生成素的免疫分析套組進行濃度檢測之研究。整體而言，於慢性腎病貓中，雖然未見血漿硫酸吲哚與紅血球生成素濃度的直接相關性，但顯示其與紅血球數及其他貧血相關指標（血紅素濃度、血容比）具有負相關性。此外，本實驗發現慢性腎病貓其血漿紅血球生成素與纖維母細胞生長因子－23間具有顯著正相關性。 關鍵字： 貓, 慢性腎病, 硫酸吲哚, 紅血球生成素, 纖維母細胞生長因子－23 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:10:13Z (GMT). No. of bitstreams: 1 U0001-2310202112170100.pdf: 3104195 bytes, checksum: 34e1271e00beb607f219553fa381ece8 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員審定 I 致謝 II 中文摘要 IV ABSTRACT VIII CHAPTER 1. INTRODUCTION 1 CHAPTER 2. LITERATURE REVIEW 3 2.1 Indoxyl sulfate and chronic kidney disease 3 2.1.1. Background of uremic toxins 3 2.1.2. Introduction of indoxyl sulfate 3 2.1.3. Pathophysiological roles of indoxyl sulfate in chronic kidney disease 3 2.2 Anemia of renal disease 5 2.2.1 Physiology of erythropoiesis 5 2.2.2 Pathophysiology of anemia in chronic kidney disease 7 2.2.3 Current management of renal anemia 8 2.2.4 Erythropoietin resistance (hyporesponsiveness) in CKD patients 9 2.2.5 Role of indoxyl sulfate in the regulation of erythropoiesis 10 2.3 Mineral homeostasis in chronic kidney disease 10 2.3.1 Normal physiology of mineral homeostasis 10 2.3.2 Introduction of fibroblast growth factor 23 (FGF23) and its cofactor 11 2.3.3 Regulation of fibroblast growth factor 23 in normal physiology 11 2.3.4 Pathophysiology of mineral homeostasis disorders and the role of FGF23 in chronic kidney disease 13 2.4 Association of erythropoietin and fibroblast growth factor 23 15 2.4.1. Regulation of erythropoietin to fibroblast growth factor 23 15 2.4.2. Regulation of fibroblast growth factor 23 to erythropoietin 16 CHAPTER 3. MATERIALS AND METHODS 17 3.1 Patients and Sample Collection 17 3.1.1. Samples and medical information collection 17 3.1.2 The enrollment and exclusion criteria of cases 17 3.2 Measurement of IS by HPLC-FLD method 22 3.2.1 Chemicals and reagents 22 3.2.2 Stock solutions and calibration standards 22 3.2.3 Sample preparation 22 3.2.4 Chromatographic system 23 3.2.5 Calibration curves and analytical method validation 23 3.3 Measurement of erythropoietin by commercial feline erythropoietin ELISA kit 24 3.4 Measurement of FGF23 by commercial feline FGF23 ELISA kit 25 3.5 Statistical analysis 26 CHAPTER 4. RESULTS 27 4.1 Validation of plasma IS, FGF23, and EPO measurement method 27 4.1.1 Validation of plasma IS measurement method by HPLC-FLD 27 4.1.2 Validation of plasma EPO and FGF23 measurement by commercial ELISA kits 31 4.2 Patients and samples collection 32 4.2.1 The IS-EPO group 32 4.2.2 The EPO-FGF23 group 33 4.3 Comparison of IS, EPO, and other clinical parameters among the control group and IRIS CKD stage 1~4 34 4.4 Comparison of IS, EPO, and other clinical parameters between anemia and non-anemia group in cats with CKD 39 4.5 Receiver operating curve (ROC) analysis between anemia and non-anemia in cats with CKD 41 4.6 Logistic regression analysis for different parameters associated with anemia in cats with CKD 41 4.7 Correlations between IS, EPO and other clinical parameters in cats with CKD 42 4.8 Comparison of IS, EPO and other clinical parameters between progression and non-progression group in cats with CKD 48 4.9 Receiver operating curve (ROC) analysis between progression and non-progression in cats with CKD 51 4.10 Logistic regression analysis for different parameters associated with progression in cats with CKD 52 4.11 Kaplan-Meier curve analysis for factors associate with 90-day progression in cats with CKD 53 4.12 Comparison of EPO, FGF23, and other clinical parameters among the control group and IRIS CKD stage 1~4 54 4.13 Comparison of plasma EPO, FGF23 and other clinical parameters between anemia and non-anemia group in cats with CKD 59 4.14 Receiver operating curve (ROC) analysis between anemia and non-anemia in cats with CKD 61 4.15 Comparison of plasma EPO, FGF23 and other clinical parameters between higher and lower phosphate group in cats with CKD 61 4.16 Correlations between EPO, FGF23 and other clinical parameters in cats with CKD 63 4.17 Comparison of EPO, FGF23 and other clinical parameters between progression and non-progression group in cats with CKD 68 4.18 Receiver operating curve (ROC) analysis between progression and non-progression in cats with CKD 70 4.19 Logistic regression analysis for different parameters associated with progression in cats with CKD 71 4.20 Kaplan-Meier curve analysis for factors associate with 90-day progression in cats with CKD 72 4.21.1 Comparison of plasma EPO other clinical parameters between anemia and non-anemia group in cats 73 4.21.2 Correlations between EPO and other clinical parameters in cats with CKD 74 4.21.3 Logistic regression analysis of plasma EPO for the progression in cats with CKD 77 CHAPTER 5. DISCUSSION 78 5.1 Plasma IS concentration in cats with CKD 78 5.1.1 Associations between plasma IS concentration and renal function 78 5.1.2 Associations between plasma IS concentration and anemia in cats with CKD 79 5.2 Plasma EPO concentration in cats with CKD 80 5.2.1 Comparison of plasma EPO concentration between healthy cats and cats with CKD 80 5.2.2 Comparison of plasma EPO concentration between anemic and non-anemic cats with CKD 81 5.2.3 The effects of ESAs on the plasma EPO concentration in cats with CKD 82 5.2.4 Associations between plasma EPO concentration and other clinical parameters in cats with CKD 83 5.3 Plasma FGF23 concentration in cats with CKD 84 5.3.1 Associations between plasma FGF23 concentration and anemia in cats with CKD 84 5.3.2 Associations between plasma FGF23 concentration and other clinical parameters in cats with CKD 85 5.4 Association between IS and EPO in cats with CKD 86 5.5 Association between EPO and FGF23 in cats with CKD 86 5.6 The capability of IS, EPO, or FGF23 to predict the development of anemia in cats with CKD 87 5.7 The association of between plasma IS, EPO, or FGF23 and the progression in cats with CKD 87 5.7.1 The association of between plasma IS and the progression in cats with CKD 87 5.7.2 The association of between plasma EPO and the progression in cats with CKD 88 5.7.3 The association of between FGF23 and the progression in cats with CKD 88 5.8 The limitations in this study 88 CHAPTER 6. CONCLUSIONS 90 REFERENCES 91" | |
| dc.language.iso | en | |
| dc.subject | 慢性腎病 | zh_TW |
| dc.subject | 硫酸吲哚 | zh_TW |
| dc.subject | 紅血球生成素 | zh_TW |
| dc.subject | 纖維母細胞生長因子－23 | zh_TW |
| dc.subject | 貓 | zh_TW |
| dc.subject | erythropoietin | en |
| dc.subject | indoxyl sulfate | en |
| dc.subject | chronic kidney disease | en |
| dc.subject | Cat | en |
| dc.subject | fibroblast growth factor 23 | en |
| dc.title | 紅血球生成素與硫酸吲哚及纖維母細胞生長因子－23在貓慢性腎病與病程進展之相關性 | zh_TW |
| dc.title | "The associations of plasma erythropoietin with indoxyl sulfate, fibroblast growth factor 23, and the progression in cats with chronic kidney disease" | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 周濟眾(Hsin-Tsai Liu),蔡沛學(Chih-Yang Tseng),吳允升 | |
| dc.subject.keyword | 貓,慢性腎病,硫酸吲哚,紅血球生成素,纖維母細胞生長因子－23, | zh_TW |
| dc.subject.keyword | Cat,chronic kidney disease,indoxyl sulfate,erythropoietin,fibroblast growth factor 23, | en |
| dc.relation.page | 98 | |
| dc.identifier.doi | 10.6342/NTU202104061 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-10-26 | |
| dc.contributor.author-college | 獸醫專業學院 | zh_TW |
| dc.contributor.author-dept | 臨床動物醫學研究所 | zh_TW |
| 顯示於系所單位： | 臨床動物醫學研究所 | |
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