Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12893
標題: 以NGAL蛋白濃度評估犬隻急性腎損傷
Neutrophil gelatinase-associated lipocalin(NGAL) levels in dogs with acute kidney injury
作者: 胡譽嚴
Hu, Yu-Yen
關鍵字: 急性腎損傷
Neutophil gelatinase-associated lipocalin
分子標的
NGAL
acute kidney injury
Biomarker
出版社: 獸醫學系暨研究所
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摘要: 腎衰竭為動物常見的疾病之一。儘管醫療水準逐漸提昇,急性腎衰竭動物之發病率和死亡率依然居高不下。在人類的醫學研究中,已建立新的急性腎衰竭診斷標準,也積極研究早期預測急性腎損傷(Acute kidney injury, AKI)的生物標記(biomarkers)。Neutrophil gelatinase-associated lipocalin (NGAL),大小為25kDa的蛋白質,其特性為藉由參與細胞中鐵的轉換,來調控腎臟細胞再生、修復及凋亡。腎臟受損的幾個小時內,其NGAL蛋白即開始大量累積於血液和尿液中,相較血清肌酸酐(creatinine)而言,NGAL更可有效應用於早期診斷腎損傷。本研究目的分為兩個部份,第一部份為發展sandwich ELISA系統應用於犬隻NGAL的測定。首先製備anti-NGAL抗體,然後比較分析自製ELISA方法和市售ELISA kit的相關性,確定自製方法可作為臨床犬隻NGAL量的偵測。此外,進一步將此ELISA應用於評估手術病犬前後NGAL量的變化。此研究共收集56隻病犬術前、術後12小時內、24小時、48小時及72小時之新鮮樣本。統計學分析結果顯示,有13隻病犬術後72小時內有AKI之狀況(AKI, 定義為血清creatinine上升≧0.3 mg/dL),其尿液中NGAL濃度術前和術後24小時相比,從84.4 pg/mL [IQR= 65.53] 上升至193.65 pg/mL [IQR= 182.78];此外,AKI組病犬在術後24小時之尿液NGAL顯著高於29隻無AKI病犬 (193.65 pg/mL [IQR= 182.78] vs. 85.05 pg/mL [IQR= 164.65], p=0.015);ROC 分析結果,尿液NGAL比較creatinine具有較佳的area under the curve (AUC, 0.765 vs. 0.558) 以預測術後24小時之急性腎損傷;此時測得NGAL濃度的cut-off point為158.8 pg/mL,敏感度達73%及特異度達80%。除此之外,其中14隻因特殊疾病併發腎功能障礙執行手術病犬,尿液NGAL和血清BUN、creatinine呈現相似的變化趨勢,其測定平均值在腎功能障礙組相較於無AKI組明顯較高,經過手術治療後逐漸降低回復。由本研究可知,自製的ELISA方法將可作為適合偵測犬隻NGAL的診斷工具;另外犬隻NGAL可作為早期診斷腎損傷的biomarker,不只如此,對於腎病的疾病進展也可作為參考指標。
Renal failure is one of the most common diseases in dogs. Despite significant improvement in therapeutics, the mortality and morbidity associated with renal failure remain high. Medical research in human has established new diagnostic criteria for acute renal failure, and focused on searching the biomarkers for prediction of acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein, which regulates renal growth, repair and apoptosis through iron transport. NGAL starts to accumulate within a few hours in the blood and urine during acute kidney injury that is earlier than serum creatinine and might be applied in early diagnosis of kidney injury. The aim of this study was to develop a sandwich ELISA method for detection of canine NGAL. Antibodies against NGAL were firstly produced, the detection performance of in-house ELISA was correlated with a commercial ELISA kit, and then the NGAL level of clinic specimens was determined. The in-house NGAL ELISA was subsequently used in evaluation of NGAL levels in urine and serum samples collected from dogs with surgery. In total, samples of 56 dogs from the animal hospitals were collected prior to operation and at various time points (12, 24, 48, 72h) following surgery. Among the samples, 13 dogs (23%) developed AKI within the 72h follow-up (AKI, defined as creatinine rise ≧0.3 mg/dL), and urine NGAL rose from median of 84.4 pg/mL [IQR= 65.53] of baseline to 193.65 pg/mL [IQR= 182.78] at 24 h post operation. Simultaneously, AKI dogs had significantly higher urine NGAL levels than those without AKI (193.65 pg/mL [IQR= 182.78] vs. 85.05 pg/mL [IQR= 164.65], p=0.015). In ROC analysis, urine NGAL had greater AUC (0.765) than creatinine did (0.558) in predicting AKI at 24 h post operation; and the cut-off point of NGAL was 158.8 pg/mL, with sensitivity and specificity 80% and 73%. Moreover, in the 14 dogs performed surgery with renal dysfunction, the alterations of urine NGAL, serum BUN and serum creatinine concentrations shared a similar trend; The average value of these proteins measured in the renal dysfunction group were significantly higher than no AKI group, and then gradually decreased post operation. Taken together, the ELISA method we developed in this study is an appropriate tool for detecting canine urine and serum NGAL. Besides, NGAL not only can be an early marker for diagnosis of AKI, but also serves as evaluation criteria for progression of kidney disease.
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