慢性腎臟病定義為單側或雙側的腎臟出現結構上或功能上進行性且不可逆性地慢性病程變化(Bartges, 2012)，逐漸損害病患生理恆定機能，並可能進一步造成腎臟的損傷與加速病程的進展，因此對於慢性腎臟疾病的早期發現與監控十分重要。在人類醫學的研究中，已指出在慢性腎臟疾病的病患可藉由非侵入性的超音波掃描檢查，測量腎臟皮質厚度作為早期偵測腎臟功能損傷的指標(Beland, et al., 2010; Takata, et al., 2016; Yamashita, et al., 2015)；然而就作者所知目前在獸醫領域還尚未有相關研究報告被提出。在本研究中，回溯收集中興大學教學醫院2012年1月至2016年12月所有被診斷為慢性腎臟疾病貓隻病例及其超音波檢查影像，並與健康貓隻超音波影像比較其腎臟尺度的變化。針對健康控制組的年齡、體重、性別進行多重線性回歸，結果僅有左腎長度與年齡(左腎: p = 0.0213, r = – 0.9895)負向線性相關，雌性因素則與雙側腎臟長度皆呈負向的線性相關性(左腎: p = 0.0408, r = – 2.7988; 右腎: p = 0.0256, r = – 2.8312)。比較控制組與疾病組的腎臟尺度指數可見皮質厚度、皮質/髓質厚度比值與腎臟長度隨病程的嚴重程度增加而有減少的趨勢，進行腎臟尺度與血清肌酐酸濃度之倒數的線性回歸分析，可見腎臟皮質具有顯著且強烈的線性相關(左腎: p < 0.0001、r = 0.6128、r2 = 36.23%；右腎: p < 0.0001, r = 0.5929, r2 = 35.15%)。進行ROC曲線分析腎臟尺度鑑別健康貓與慢性腎臟病貓之能力，腎臟皮質厚度具有良好的診斷能力(左腎: AUROC = 0.95；右腎: AUROC = 0.93)，將左腎皮質厚度的分界值訂為0.466公分具有90.0%的敏感度與94.7%的特異度，將右腎皮質厚度分界值訂為0.45公分具有83.3%的敏感度與94.7%的特異度。雖然皮質/髓質厚度比值亦有良好的診斷能力，但其數值的測量在在不同觀測者間相對不穩定固非穩定評估的指標。根據以上結果，所有腎臟尺度中對於反應慢性腎臟病貓隻腎臟損傷程度以腎臟皮質厚度最佳，而在健康成年貓隻中，體重、年齡、性別皆未對腎臟皮質厚度有顯著影響，因此，在慢性腎臟疾病貓隻測量腎臟皮質厚度相對於傳統使用的腎臟長度能更好的去評估腎臟功能損傷。

Chronic kidney disease (CKD) is a progressive and irreversible loss of renal function over a period of months to years.(Bartges, 2012) In clinical practice, bipolar renal lengths measured by ultrasound is a useful index to initially evaluate the severity of renal atrophy in CKD patients in veterinary medicine. It has been reported in human medicine that measurement of left renal cortical thickness could evaluate the loss of renal function in patients with CKD.(Beland, et al., 2010; Takata, et al., 2016; Yamashita, et al., 2015) To the best of the author’s knowledge, literatures have not described the correlation between renal cortical thickness and renal function in CKD cats. Therefore, the main purpose of this study is to clarify the relationship between renal dimensional indices and the severity of chronic kidney disease in cats. Nineteen clinically healthy cats were recruited as control group. The medical record database of veterinary medical teaching hospital of National Chung Hsing university from January 2012 to December 2016 with the clinical diagnosis of CKD cats were reviewed. Totally, thirty CKD cats met the inclusion criteria of disease group. Measurement of the renal length, cortical thickness, medullary thickness, and corticomedullary ratio (C/M ratio) of each kidney of all of the cats were recorded. The result of multiple linear regression in control group including age, body weight, and gender showed the left renal length had significantly negative correlation with age (p = 0.0213, r = – 0.9895) and female gender (p = 0.0478, r = –2.7995). The right renal length only had significantly negative correlation with female gender (p = 0.0031, r = – 3.8707). Both the renal cortical thickness and C/M ratio did not exist significant correlation with age, body weight and female gender. Furthermore, comparing control group and disease groups, the results showed negative correlations in cortical thickness, C/M ratio, and renal length with the decrease of renal function. The cortical thickness presented the highest linear correlation with reciprocal value of serum creatinine concentration (left: p<0.0001, r2 = 36.23%; right: p<0.0001, r2 =35.15%). According to ROC curve analysis between the control group and disease groups, the cut–off value of cortical thickness was set as 0.466 cm with 90.0% sensitivity and 94.7% specificity in left kidney and 0.45 cm with 83.3% sensitivity and 94.74% specificity in right kidney. Although the CM ratio also presented excellent diagnosis performance, the inconsistent measurement between observers revealed that C/M ratio was unstable for evaluation. In conclusion, measurement of renal cortical thickness could detect loss of renal function earlier and have lesser confounding factors than the renal length that was used traditionally in CKD cats.

中文摘要 i
Abstract iii
Contents v
Table contents vii
Figure contents viii
List of abbreviations ix
Chapter 1 Introduction 1
Chapter 2 Literature Reviews 3
2.1. Chronic kidney disease in cat 3
2.1.1. Epidemiology 3
2.1.2. Pathophysiology 3
2.1.3. Clinical syndrome presentation and clinicopathologic findings 6
2.1.4. IRIS CKD staging system 9
2.2. Diagnostic imaging examination for CKD 11
2.2.1. Radiography for CKD 11
2.2.2. Ultrasonography for CKD 13
Chapter 3 Material and Methods 19
3.1. Control group 19
3.1.1. Selection criteria 19
3.1.2. Ultrasound examination and ultrasound–guided cystocentesis 20
3.1.3. Ultrasonographic renal indices measurement and evaluation 20
3.2. Disease group 21
3.2.1. Selection criteria 21
3.2.2. CKD disease grouping criteria 21
3.2.3 Ultrasonographic renal indices measurement and evaluation 22
3.3. Statistical analysis 22
Chapter 4 Results 26
4.1. Signalment 26
4.1.1. Control group 27
4.1.2. Disease group one 27
4.1.3. Disease group two 28
4.2. Abnormal Ultrasound finding (table 4–4) 28
4.2.1. Disease group one 28
4.2.2. Disease group two 28
4.3. Renal dimension indices of control group 28
4.3.1. Intra–observer variability 29
4.3.2. Inter–observer agreement 29
4.3.3. The correlation of renal dimensional indices with age, body weight, and gender in control group. 29
4.4. Renal dimension indices of disease group 30
4.4.1. The relationship of renal dimensional indices between groups 30
4.4.2. The linear relationship between renal dimensional indices and clinical pathologic indices 31
4.4.3. The diagnostic performance of renal dimensional indices 31
Chapter 5 Discussion 42
5.1. The signalment, clinical presentation and ultrasound image findings 42
5.2. The performance of the renal ultrasound examination 44
5.3. The value of renal dimensional indices 45
5.3.1. The normal distribution of renal dimensional indices and the influence of confounding factors 45
5.3.2. The relationship of renal dimensional indices between different CKD stage. 49
5.3.3. The diagnosis performance of renal dimensional indices in CKD cats. 50
5.4. Limitations 50
5.5. Conclusion 51
Reference 52
Appendix 62

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