隨著醫療科技的發達，對先天性阻塞性腎病變的病理機制雖有長足的研究與進展，但卻仍是各年齡層末期腎病變的主要因素之一。尤其是幼兒的腎臟影響更劇，此可由文獻中阻塞性腎病變約佔嬰兒和兒童末期腎衰竭之20﹪而得知，其中尤以先天性腎盂輸尿管阻塞所佔之比例最高。目前在產前超音波的廣泛施行下，先天性腎盂輸尿管阻塞的患童常可被早期發現，但何時是最好的手術介入治療時機以保留最佳的殘餘腎功能則仍未有定論。於此論文第一個計畫中，我們試由經皮腎臟造口術之方法收集阻塞側腎臟所過濾的尿液與相對側腎臟所過濾出之尿液相互比較分析阻塞後腎功能之差異，其中涵蓋過濾分率、腎小管功能、尿液中所表現的細胞激素、生長激素濃度與細胞凋亡之指標；此外並與術前及術後之核醫腎功能（DTPA）評估以分析其相關預後因素。由此實驗證明，腎功能會因阻塞而下降，且吾人建議阻塞側腎臟之核醫腎功能介於35-40％時則應建議接受手術即可達最大的腎功能保留程度；若近端腎功能受影響時也代表著預後不佳。尿液中所表現的細胞激素、生長激素濃度與細胞凋亡之指標則代表著阻塞後腎臟器官之反應，其程度之高低並不一定與預後相關。
　　另一方面，於臨床的觀察中我們也注意到腎盂輸尿管處的移行性上皮細胞可見到增生或伴隨單核性發炎細胞的浸潤現像；其中部份患童組織中的發炎細胞可伴隨大量的嗜伊紅性白血球。吾人也推測移行性上皮細胞的生長異常可能代表者局部發炎免疫過程之表徵，此現像也可解釋先天性腎盂輸尿管狹窄程度於臨床上惡化的可能性。依此論點將可說明部分患者其臨床表現會由非阻塞性水腎發展成阻塞性水腎的事實。於本論文的第二個計畫則是研究探討先天性腎盂輸尿管狹窄中狹窄處移行性上皮細胞的病理特徵，並藉由免疫組織染色方法、原位雜交染色與尿液細胞激素、生長激素濃度之分析以探討上皮細胞之免疫反應。在此研究中，吾人發現先天性腎盂輸尿管狹窄處皆會表現程度不一的發炎細胞浸潤與嗜伊紅性白血球的存在；移行性上皮細胞也可分泌表現出間白素5（interleukin 5）與相關之細胞激素（如eotaxin）。此外於狹窄處之基質與平滑肌內也可見到顯著被活化的肥大細胞存在。依此結果，吾人也證明了移行性上皮細胞於先天性腎盂輸尿管狹窄疾病的免疫角色。因此我們認為釐清未曾被人注意之『移行性上皮細胞之異常』於先天性腎盂輸尿管阻塞病變的角色是重要且必需的。我們也希望藉此研究為基石，希望未來更能探討瞭解致病機制並進一步研究訊息傳送之基礎；同時也希望於另一方面未來也可提供探討此疾病內科藥物治療的可行性。

　Ureteropelvic junction obstruction (UPJ-O) is defined as a functional or anatomic obstruction to urine flow from the renal pelvis to the ureter that may result in symptoms or renal damage. It is the most common fetal urinary tract anomaly identified in prenatal screening of pregnant women and the neonatal kidney is more susceptible to injury than the adult kidney. Although obstructive nephropathy is a major cause of renal insufficiency at all ages, the functional consequences of relief of obstruction on the developing kidney are poorly understood. In first part of this thesis, we evaluated with 99m technetium-labeled diethylenetriaminepentaacetic acid furosemide renal scans (DTPA) to determine the correlation of split tubular function tests, growth factors and renal function under the hypothesis that functional changes in the obstructed kidney before pyeloplasty could be used to predict of its subsequent function after pyeloplasty. In our results, impaired renal function of creatinine clearance, tubular function, cellular apoptosis, excretion of cytokines and growth factors were changed significantly in obstructed side kidney. Proximal tubular dysfunction, such as increased percent fractional excretion of sodium and chloride, and initial DTPA =<35%, suggested a high possibility of poorly preserved renal outcome. Besides, a high urinary level of epidermal growth factor might be a potential indicator of preservation of renal growth.
　The main histologic abnormalities in UPJ-O showed fibrosis of the mucosa and fibromuscularis tunicae along with changes in the number, distribution, and size of the smooth muscle cells in the ureteral wall. However, we observed that both mononuclear cell infiltration and eosinophil infiltration were also frequently found in UPJ-O segments and were combined with urothelium aberration or hyperplasia. We, therefore, hypothesized that urothelial reaction in UPJ-O might be caused by an immunoregulatory reaction and this would exacerbate the degree of obstruction. We investigated the immunopathological characteristics of and cytokine production by urothelium in children with congenital UPJ-O by immunohistochemical (IHC) study, in situ hybridization (ISH) and urinary enzyme-linked immunosorbent assay (ELISA). Results showed that variable degrees of inflammatory cell and eosinophil infiltration were in UPJ-O, which were combined with overexpressed Ki67 in urothelium. Besides, augmented expression of interleukin 5 (IL-5) and eotaxin detected by IHC and ISH and enhanced degranulation of tissue mast cells were observed in the urothelium of UPJ-O segments. Significantly higher levels of urinary IL-5, IFN-gamma, and eotaxin were also detected in urine collected from the obstructed kidney. Finally, we demonstrated that urothelium, like intestinal and respiratory epithelia, would play an active role in the immunoregulatory process, and possibly contribute to the exacerbation of the pathogenesis of congenital UPJ-O. The result of our second study suggested that when insult or stimulation occurs in urothelium, which will further initiate the in situ urothelium immune response and then trigger infiltration of inflammatory cells consequently. Further more, after the interaction between inflammatory cells with mesenchymal cells, this can finally result or exacerbate the lamina collagen fibrosis or muscular hypertrophy.

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