透過尿蛋白與尿肌酸酐比值檢測評估Rituximab（莫須瘤）治療對於紅斑性狼瘡腎炎患者的腎臟保護效果，單一醫學中心經驗

The Renal Protective Efficacy of Rituximab (RTX) in Systemic Lupus Erythematosus (SLE) Patients, evaluated via Urine Protein to Creatinine Ratio (UPCR), a Single Center Experience

Objective: The primary objective of this retrospective study is to evaluate the renal protective efficacy ofRituximab in patients with systemic lupus erythematosus (SLE) via their urine protein to creatinine ratio(UPCR) in a single medical center in Taiwan. For the purposes of this study, a slight elevation of UPCR istaken as one of the early manifestations of lupus nephritis (LN).Methods: Patients (N=18) diagnosed with SLE according to the Systemic Lupus InternationalCollaborating Clinics (SLICC) 2012 criteria received Rituximab therapy (500 mg on weeks 0, 2, 24, and26) between January 2013 and May 2018. Primary end point is renal response at week 48.Results: Complete renal response (CRR, inactive urinary sediment and UPCR< 0.5 mg/mg withoutsignificant deterioration of renal function (≧50% reduction in the eGFR from baseline)) after Rituximabtherapy was observed in seventy-two percent of the patients (N=13/18). The overall improvement of allindicators was significant. The mean baseline UPCR value was 1.32 ±1.96 mg/mg and 0.32±0.38 mg/mg at week 48 (p=0.0043) (Wilcoxon signed-rank test). The mean baseline value for C3 complementwas 72.49 ±30.63 mg/dL and 89.88±24.77mg/dL at week 48 (p=0.002). The mean baseline of antidsDNAantibody titer was 216.68±227.13 WHO units/mL and 116.04±104.93 WHO units/mL at week 48(p=0.0071). Glucocorticoid-sparing effect was also observed (baseline prednisolone equivalent dose: 15.69±9.65 mg/day; week 48 mean: 9.16±5.56 mg/day, p=0.0046).Conclusion: Renal protective efficacy could be seen in patients who receive Rituximab therapy during theearly stages of possible LN. 目的：採回朔性研究法研究台灣單一醫學中心族群中接受Rituximab（莫須瘤）治療的紅斑性狼瘡病人是否有達到腎臟保護的效用，腎臟功能評估採用尿蛋白與尿肌酸酐比值。方法：從2013年一月至2018年五月，共18位病人依照SLICC 2012標準診斷紅斑性狼瘡診斷，收案條件包含：尿蛋白與尿肌酸酐比值≥0.15毫克比毫克，或尿液試紙分析≥1＋的尿蛋白或尿液沉澱分析有≥5紅血球／高倍視野或含有任何紅血球圓柱體，且須排除其他可能原因（如腎結石，泌尿道發炎…等）；類固醇使用劑量必須小於每日每公斤0.5毫克普利多寧等效劑量（最高只能至每日30毫克普利多寧等效劑量）；48周的追蹤期間不能使用癌德星（cyclophosphamide），其接受Rituximab治療流程為第0、2、24及26週給予500mg點滴注射，主要試驗指標為第48週的腎臟治療後反應。結果：完全腎臟反應系指並沒有活化的尿液沉積，尿蛋白與尿肌酸酐比值小於0.5mg／mg，沒有明顯的腎臟功能惡化。我們的研究族群有13位病人（72%）達到此標準，治療前後UPCR平均值（第0週1.32±1.96毫克比毫克；第48週：0.32±0.38毫克比毫克，p＝0.0043（魏克生等級和檢定）有達到統計學上顯著下降。血清體C3數值（第0週72.49±30.63 mg／dL；第48週：89.88±24.77mg／dL）也有達到統計學顯著上升，抗DNA抗體下降值同樣達到統計學顯著差異（第0週：216.68±227.13；第48週：116.04±104.93 WHO units／mL，p＝0.0071）。同樣地，類固醇減量效果也達到統計學上顯著差異（培尼皮質醇等效劑量平均值第0週15.69±9.65 mg／day；第48週：9.16±5.56，p＝0.0046）。結論：Rituximab在可能為早期狼瘡性腎炎的病人治療上似乎可以達到保護腎臟的功效。