急性腎損傷於密西西比紅耳龜臨床病理及組織病理之連續性評估

Abstract

腎臟疾病在龜類為常見的疾病，目前在臨床實驗診斷方面尚未發展出可靠的診斷工具可以早期偵測腎臟損傷，因而往往在診斷出腎臟疾病時，已錯失讓腎臟功能再恢復的最佳時機，最終造成龜類的死亡，故如何能夠早期且有效偵測到腎損傷，進行早期治療，免於錯失腎臟能夠早期恢復功能，降低因腎臟疾病等致死的問題為本研究之主要目的。本實驗以慶大黴素(gentamicin)誘發密西西比紅耳龜的腎臟產生退行性病變，造成龜類急性腎損傷後，連續監測其血液生化指數及尿液中酵素的變化，同時與其腎臟組織病理作比較，以期找到早期偵測的方式並確立此模式。結果顯示，投藥組與對照組在腎臟組織病變的平均分級上明顯不同，表示gentamicin確實可誘發投藥組腎臟的退行性變化；進一步分析不同組織病理分級下各檢驗值的結果顯示，血中AST、ALKP、CK以及ALT濃度在不同的分級下有顯著差異；針對對照組及投藥組進行各項檢驗值的統計分析，結果指出，血液生化指數與尿液中酵素的變化相較於全血球計數可以更早反映出急性腎損傷，並且在血中尿酸值上升之前，可觀察到血中的AST、ALT、LDH與CK值在腎損傷發生後，濃度上升的趨勢會更早出現，而尿液中AST與phosphorus值也有相同的趨勢。因此，未來在臨床診療上，即使病患血中尿酸濃度並未升高，但若見到血中AST、ALT、LDH以及CK值同時有上升趨勢時，可合理懷疑已發生腎損傷的狀況，並立即進行治療或校正其環境因素。值得注意的是，由於血中酵素來源器官範圍廣，敏感性高但特異性偏低，因此在判讀上仍要小心區分其他臟器的問題，未來仍可以此模式進行相關研究，發掘出特異性更高的生物標記，以利診斷；在臨床診療上也期待可以收集更多病例，來印證本次研究的分級方式，作出更準確的參考依據。

Renal disease is one of the most common problems in chelonian patients. So far, there isn’t any reliable index in clinical laboratory medicine to diagnose early renal injury in chelonian. As a result it was often too late to intervene when renal disease is diagnosed, with the patient end up dead. Therefore, the aim of this study is to find a way to detect renal injury earlier and effectively, to treat if necessary, to let the kidneys recover in early stage, and to decrease the mortality caused by renal diseases. In this study, acute kidney injury (AKI) in red-eared slider (Trachemys scripta) was induced via injection of gentamicin, which would cause degeneration of proximal renal tubules. In order to find a way to early detect acute kidney injury and establish an AKI model in red-eared slides, serial monitoring of blood biochemistry and urine enzyme were performed, and comparison between them and renal histology was made. Results revealed that renal histopathology grading between control group and treatment group was significantly different, which proved that gentamicin could induce renal injury in the treatment group. Concentration of plasma AST, ALKP, CK and ALT were different significantly between different histopathologic grades (p < 0.05). Between the control group and treatment group, the statistic results revealed that plasma biochemistry indices and urine enzymes response earlier than complete cell count in renal injury. Moreover, before plasma uric acid was elevated, the rising trend of plasma AST, ALT, LDH, CK and urine AST and phosphorus could be observed. According to this study, as long as plasma concentration of AST, ALT, LDH and CK of patients are elevated simultaneously, even without the elevation of plasma uric acid, renal injury could still be considered as an underlying problem. And under such situation, treatment or improvement of husbandry should be implemented immediately. However, the sources of these blood enzymes are variable with high sensitivity but low specificity. It is very important to differentiate other visceral problems from renal disease. This study was a preliminary study of AKI in turtles, and the AKI model could be further used to investigate for more specific biomarkers. Hopefully by collecting more cases, the accuracy of the grading system used in this study can be confirmed to actually apply the system in practice.