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題名 | Low-Dose Mycophenolate Mofetil Therapy for Taiwanese with Refractory Glomerulonephritis--Emphasize the Effect on Membranous Nephropathy=頑固性腎絲球腎炎的MMF治療 |
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作者 | 林婉婷; 高雅惠; 郭士禛; 宋俊明; 陳芬芬; 黃建鐘; | 書刊名 | 臺灣腎臟醫學會雜誌 |
卷期 | 20:2 民95.06 |
頁次 | 頁90-97+150 |
分類號 | 415.812 |
關鍵詞 | 腎絲球腎炎; 糖質類固醇; 劑量; 膜性腎病變; 尿蛋白; Glomerulonephritis; Steroids; Mycophenolate mofetil; MMF; Dosage; Membranous nephropathy; Proteinuria; |
語文 | 英文(English) |
中文摘要 | 在台灣,腎絲球腎炎(Glomerulonephritis, GN)是造成末期腎病(end-stage renal disease, ESRD)的最主要原因之一,治療腎絲球腎炎藥物,類固醇是第一線用藥;若失敗或復發時,可併用其他免疫抑制劑(immunosuppressants),但因具有細胞毒性,會引發各種副作用。Mycophenolate mofetil(MMF),首先應用於腎移植,也用來治療器官移植以外疾病(如:腎絲球腎炎和自體免疫疾病),但其適當的劑量未明。我們嘗試以回溯性研究方式,從2002年10月至2003年4月,分析本院十七位GN患者對MMF治療之反應,其中七位為膜性腎病變(MN),五位為微細病變(MCD),以及其他組五位,包括:甲型免疫球蛋白腎病變(IgAN)一位,局部節段性腎絲球硬化(FSGS)兩位和狼瘡性腎炎(lupus nephritis, LN)兩位。男九位,女八位,平均年齡為40.9±14.3歲。他們皆曾接受三個月以上MMF之治療且對類固醇有依賴性(十位)和抗性(兩位),或曾使用其他免疫抑制劑,但反應不佳或復發(五位)。MMF治療預後的變數,包括:每日尿蛋白流失量(daily protein loss, DPL),血清白蛋白、膽固醇、血清肌酸酐(serum creatinine, SCr)和肌酸酐廓清率(CCr);並以多變異分析法找出有意義的DPL預測因子。主要是評估患者接受MMF治療前後的DPL和SCr之變化,以中位數(範圍)表示:也評估患者在MMF治療前後的CCr、血清白蛋白和膽固醇濃度之變化,並觀察MMF的副作用以及類固醇和其他藥物(ACEIs、ARBs或statins)的併用情形。 MMF治療劑量與療程,以每天0.75(0.5-1)克和治療14(3-49)個月,GN患者的DPL,由治療前4.8(1.7-15)克,降為2.3(0.3-14.1)克(p=0.009);治療前後的SCr沒有差異(1.0 vs. 1.0 mg/dL,p>0.05),且CCr、血清白蛋白和膽固醇濃度也沒差異。其中MN患者對MMF治療的反應最好,DPL由治療前的4.8(1.8-8.6)克降至0.4(0.3-2.3)克(p=0.018),血清白蛋白由3.3mg/dL增至3.8mg/dL(p=0.042),膽固醇由290mg/dL降至213mg/dL(p=0.028)。MCD患者在MMF治療前後的DPL,SCr,CCr,血清白蛋白和膽固醇濃度,都不具顯著差異(p>0.05)。其他組治療後,DPL由4.8克降至3.4克(p=0.043)。安全方面,MMF的耐受性良好,未出現嚴重胃腸或白血球降低的副作用。單變項分析發現MN者接受MMF治療容易降低DPL;多變項分析中,併用ACEIs或ARBs、未使用過免疫抑制劑和MN患者,以MMF治療容易降低其DPL。因此,MMF對類固醇或其他免疫抑制劑反應不佳的GN患者,可有效降低DPL,且穩定其腎功能。而MN患者,除降低DPL外,會改善血中白蛋白和膽固醇值;但MN患者若對MMF未有明顯反應,可考慮提高MMF的治療劑量或以其他免疫抑制劑(如:環孢靈)治療。未來可增加病人數或作前瞻性研究,以評估MMF對GN的確切療效。 |
英文摘要 | Background: Glomerulonephritis (GN) is a major cause of end-stage renal disease in Taiwan. Mycophenolate mofetil (MMF), has demonstrated some efficacy in the treatment of glomerular diseases. However, the adequate dose was not well defined. In this study, we evaluate the efficacy of low-dose MMF therapy for refractory GN in Taiwanese. Methods: Seventeen Taiwanese with biopsy-proven GN, who had received low-dose MMF therapy (0.5-1 g/day) for at least three months because of poor response or relapsing after steroids (dependence in 10 cases and resistance in 2), cyclosporin A (CsA) and/or cytotoxic therapy (in 5), were eligibly enrolled into this retrospective study. Therapeutic outcome variables were determined by daily protein loss (DPL), serum albumin, cholesterol, serum creatinine, and creatinine clearance before and after MMF therapy. Multivariate analysis was used to identify significant predictors of DPL reduction. Results: The majority (15 of 17, 88.2%) of patients had primary GNs, including: membranous nephropathy (MN, n=7), minimal change disease (n=5), focal and segmental glomerulosclerosis (n=2), and IgA nephropathy (n=1). The median (range) dose and duration of MMF therapy in these patients were 0.75 (0.5-1.0) g/day and 14 (3.0-49.0) months. Overall, the DPL decreased by a median of 65.0% (from 4.8 to 2.3 g/day) (P=0.009), but there was no significant change in other outcome variables. Furthermore, MN patients had significant improvement in DPL (from 4.8 to 0.4 g, P=0.018), serum albumin (from 3.3 to 3.8 g/dl, P=0.042) and cholesterol (from 290 to 213 mg/dl, P=0.028) after low-dose MMF therapy. Generally, side effects of low-dose MMF were uncommon and mild. Significant predictors of DPL reduction included concomitant use of angiotensin-converting enzyme inhibitor/angiotensin Ⅱ receptor antagonist, no previous treatment of CsA/cytotoxic drugs, and MN patients. Conclusions: Low-dose MMF therapy can modestly improve DPL and preserve renal function without notable side effects in Taiwanese with refractory GN, especially in MN. This study also suggests that effective doses of MMF may be lower in MN than other GNs. |
本系統之摘要資訊系依該期刊論文摘要之資訊為主。