目的 包囊性腹膜硬化症在慢性腹膜透析病患中為罕見狀況，但若發生則會帶來嚴重之併發症及高死亡率。包囊性腹膜硬化症中，因有微小血管病變、發炎以及嚴重腹膜硬化，進而造成腸子包覆及阻塞的情形。考量其高死亡率及高併發症，早期診斷包囊性腹膜硬化症並介入且預防併發症的發生尤為重要。於本研究中，藉由已知包囊性腹膜硬化症的致病機轉，探討腹膜透析液之生物標記於未來新產生包囊性腹膜硬化症或腹膜功能變化之相關性，並同時探討於包囊性腹膜硬化患者中，腹水生物標記對於預後之相關性。

方法 於第一部分，共收入16位於2016至2020年間在成大醫院因包囊性腹膜硬化症之嚴重症狀需要開刀的病患，收集手術前或術中腹水並測量TGF-?、VEGF、MMP2及PAI-1的濃度，同時收集腹膜病理報告及電腦斷層影像之報告，預後定義為持續追蹤病患至2020年底是否有死亡或術後併發症。研究中比較腹水生物標記、影像及病理報告與病患預後之相關性。於第二部分，共收入132位於2016至2020年間在成大醫院持續透析之腹膜透析患者，於每年定期施作之腹膜平衡試驗中收集腹膜透析液並測量TGF-?、VEGF、MMP2及PAI-1的表現量，並比較生物標記於相關未來預後包含有症狀之包囊性腹膜硬化症、透析技術性失敗或腹膜功能失能之關聯性。同時亦於2020年中收集第二次之腹膜透析液並檢驗生物標記及評估其隨時間之變化趨勢及穩定性。最後利用邏輯斯回歸分析挑選適當生物標記及臨床變項建立列線圖。

結果 於開刀且產生併發症病患，有較高之C-反應蛋白數值。此外亦發現腹水中VEGF濃度及血管增生之病理表現有增加之趨勢。另一部分，透析液中PAI-1的表現量與未來有症狀之包囊性腹膜硬化症之發生有關聯性，此外，於未來腹膜功能失能，透析液中PAI-1及MMP2的表現量有著高關聯性。並且亦提出預測包囊性腹膜硬化症以及腹膜功能失能之列線圖。

結論 透析液PAI-1的表現量於預測３年後有症狀之包囊性腹膜硬化症之發生及腹膜功能失能有其角色。此外，透析液MMP2的表現量可找出３年後腹膜功能失能之風險族群。

PURPOSE. Encapsulated peritoneal sclerosis (EPS) is a rare disease in chronic peritoneal dialysis (PD) patients but carries devastating complication and high mortality. EPS is characterized by microangiopathy, inflammation and extreme peritoneal sclerosis resulting in intestinal encapsulation and obstruction. Concerning about high mortality and morbidity, early EPS detection is important for intervention and avoid further complication. We hypothesize that dialysate effluent biomarker, based on known EPS mechanism, would be correlated with future EPS incidence or peritoneum function change. We would also investigate ascites biomarker role with mortality and morbidity in EPS patients.

METHODS. In the first part, 16 EPS patients with operation for EPS symptoms relief in National Cheng Kung University between year of 2016 to 2020 were included. Ascites obtained before or during operation were collected. Ascites TGF-?, VEGF, MMP2 and PAI-1 levels were measured. Peritoneum pathologic findings and computed tomography (CT) radiologic findings were reviewed. Outcome of mortality or peri-operative morbidity were followed till December 2020. We compared ascites biomarkers, radiologic and pathologic finding with outcomes. In the second part, we enrolled 132 PD patients in our hospital since 2016. Clinical characteristics, PD settings and associated parameters, peritonitis history and serial laboratory data were prospectively collected. Dialysate TGF-?, VEGF, MMP2 and PAI-1 levels were measured in peritoneal dialysate effluent obtained during yearly peritoneal equilibration test (PET). We followed our patients till end of 2020. We assessed the relationship between biomarker appearance rate and the development of outcomes of symptomatic EPS, technique failure or peritoneal membrane dysfunction. Meanwhile, we longitudinally repeated effluent biomarkers appearance rate in 2020 and evaluate presentation trend and stability. We would also build nomogram for risk prediction based on logistic regression analysis results.

RESULTS. Elevated CRP level trend was associated with peri-operative morbidity. Increased ascites VEGF level and angiogenesis in pathologic finding were observed in surgical EPS patients with morbidity. Besides, higher dialysate PAI-1 appearance rate was associated with symptomatic EPS incidence. In outcome of peritoneal membrane dysfunction, significant effluent PAI-1 and MMP2 appearance rate correlation were found. We also proposed nomogram for risk prediction in symptomatic EPS and peritoneal membrane dysfunction.

CONCLUSION. Dialysate PAI-1 had role in predict symptomatic EPS incidence and peritoneal membrane dysfunction 3 years later. Dialysate MMP2, in the other hand, identified risk population of peritoneal membrane dysfunction 3 years later.

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