徐毅芳 徐瑩
[摘要] 目的 觀察他克莫司聯(lián)合糖皮質(zhì)激素治療特發(fā)性膜性腎病的療效。 方法 選擇2012 年12月~2014年12月于我院住院治療的特發(fā)性膜性腎病患者120例,隨機(jī)分為觀察組和對照組,每組各60例,兩組均予常規(guī)治療和對癥治療。觀察組同時聯(lián)合他克莫司聯(lián)合糖皮質(zhì)激素治療,治療后比較兩組的臨床療效以及比較兩組患者尿蛋白、血清白蛋白、血肌酐水平治療前后的變化。 結(jié)果 觀察組治療后未緩解3例,對照組治療后未緩解18例。觀察組治療后的總緩解率(95.00%)顯著高于對照組(70.00%),組間療效比較有統(tǒng)計學(xué)差異(P<0.05)。兩組治療前尿蛋白、血清白蛋白、血肌酐水平比較無統(tǒng)計學(xué)差異(P>0.05);治療后兩組尿蛋白水平顯著降低,血清白蛋白顯著升高,差異有統(tǒng)計學(xué)意義(P<0.05);且觀察組患者治療后尿蛋白水平顯著低于對照組,血清白蛋白顯著高于對照組(P<0.05)。但兩組患者血肌酐水平治療前后以及組間比較未見明顯差異(P>0.05)。 結(jié)論 他克莫司聯(lián)合糖皮質(zhì)激素治療特發(fā)性膜性腎病療效顯著,可以顯著改善腎功能,值得推廣和應(yīng)用。
[關(guān)鍵詞] 特發(fā)性膜性腎?。凰四?;糖皮質(zhì)激素;血肌酐
[中圖分類號] R692 [文獻(xiàn)標(biāo)識碼] B [文章編號] 1673-9701(2017)12-0122-03
[Abstract] Objective To observe the efficacy of tacrolimus combined with glucocorticoid in the treatment of idiopathic membranous nephropathy. Methods 120 patients with idiopathic membranous nephropathy who were hospitalized in our hospital from December 2012 to December 2014 were selected. 120 cases of idiopathic membranous nephropathy were randomly divided into the observation group and the control group, with 60 cases in each group. Both groups were given routine treatment and symptomatic treatment. The observation group was treated with tacrolimus combined with glucocorticoid. After treatment, the clinical efficacy was compared between the two groups, and changes of urinary protein, serum albumin and serum creatinine were compared before and after the treatment. Results In the observation group, 3 cases were not remission after the treatment and 18 cases were not remission in the control group after treatment. The total remission rate(95.00%) in the observation group after the treatment was significantly higher than that in the control group(70.00%), and the difference in the efficacy between groups was statistically significant(P<0.05). There were no statistically significant differences in urinary protein, serum albumin and serum creatinine before the treatment between the two groups(P>0.05); after treatment, the levels of urine protein were significantly decreased, and serum albumin was significantly increased in both groups. The differences were statistically significant(P<0.05); and the level of urinary protein in the observation group was significantly lower than that in the control group after the treatment, and serum albumin was significantly higher than the control group. There was statistically significant difference between the two groups(P<0.05). However, there was no significant difference in serum creatinine level before and after treatment and between the two groups(P>0.05). Conclusion Tacrolimus combined with glucocorticoid in the treatment of idiopathic membranous nephropathy has a significant efficacy, which can significantly improve the renal function, and is worthy of promotion and application.
[Key words] Idiopathic membranous nephropathy; Tacrolimus; Glucocordicoid; Serum creatinine
特發(fā)性膜性腎病(idiopathic membranous nephropathy,IMN)約占膜性腎病(membranous nephropathy,MN)的 2/3,是中老年原發(fā)性腎病綜合征患者常見的病理類型,高峰年齡為50~60歲[1-2]。糖皮質(zhì)激素為治療IMN的常用藥物,但單用激素不能明顯降低尿蛋白,不推薦單獨應(yīng)用[3-5]。他克莫司(tacrolimus,TAC)是一種新型強(qiáng)效免疫抑制劑,其作用機(jī)制雖與環(huán)孢素類似,但免疫抑制作用是環(huán)孢素的數(shù)十倍甚至百倍[6]。本研究旨在探討他克莫司與糖皮質(zhì)激素聯(lián)合應(yīng)用治療特發(fā)性膜性腎病的療效,現(xiàn)報道如下。
1 資料與方法
1.1一般資料
選擇2012年12月~2014年12月于我院住院治療的特發(fā)性膜性腎病患者120例,患者治療前3個月內(nèi)未使用過糖皮質(zhì)激素或免疫抑制劑,均簽署知情同意書,排除嚴(yán)重的肝、腎功能不全,股骨頭壞死、活動性消化性潰瘍、藥物過敏者及妊娠或哺乳期女性。年齡20~70歲,平均(41.3±7.8)歲,平均病程(5.1±1.2)年,合并腎小球硬化13例。120例特發(fā)性膜性腎病患者隨機(jī)分為觀察組和對照組,每組各60例,兩組患者的一般資料比較,差異無統(tǒng)計學(xué)意義(P>0.05),具有可比性。
1.2 治療方法
兩組患者根據(jù)血壓、血脂情況針對性選用血管緊張素轉(zhuǎn)換酶抑制劑、血管緊張素II受體拮抗劑、羥甲基戊二酰輔酶 A 還原酶抑制劑等藥物。當(dāng)血清白蛋白低于20 g/L 時加用低分子肝素鈉抗凝,預(yù)防血栓形成。兩組均口服潑尼松片,起始劑量為 0.75 mg/(kg·d),口服8~12 w 后開始進(jìn)行減量,每2周減 5 mg,6 周后每月減 5 mg,3 個月后每月減 2.5 mg,減至 15 mg/維持治療不超過 3 個月,此后每月減 2.5 mg,減至10 mg維持治療。觀察組同時聯(lián)合他克莫司治療,每日予他克莫司30 mg,服用8周后每 2 周每日用量減少5 mg,維持劑量為每日 5~10 mg。每月檢測 1 次他克莫司的血藥濃度,要求6 個月內(nèi)將血藥濃度維持在 5~10 μg/L,根據(jù)血藥濃度調(diào)整用藥劑量,但不能超過 0.15 mg/(kg·d)治療。兩組總療程為12個月。
1.3 療效評價
完全緩解為水腫消失,24 h 尿蛋白定量<0.3 g,血清白蛋白>35 g/L,腎功能正常;部分緩解為水腫減輕,24 h尿蛋白定量下降>50%,血清白蛋白30~35 g/L,腎功能好轉(zhuǎn)或無變化;未緩解為水腫無改善,24 h尿蛋白定量下降<50%,血清白蛋白<30 g/L,腎功能惡化[7]。
1.4 統(tǒng)計學(xué)方法
數(shù)據(jù)分析采用SPSS20.0統(tǒng)計分析軟件,計量資料采用t檢驗,計數(shù)資料采用χ2檢驗,P<0.05表示差異具有統(tǒng)計學(xué)意義。
2 結(jié)果
2.1 兩組臨床療效比較
見表1,觀察組治療后未緩解3例,對照組治療后未緩解18例。觀察組治療后的總緩解率(95.00%)顯著高于對照組(70.00%),組間療效比較有統(tǒng)計學(xué)差異,差異具有統(tǒng)計學(xué)意義(P<0.05)。
2.2 兩組患者尿蛋白、血清白蛋白、血肌酐水平治療前后比較
見表2。兩組治療前尿蛋白、血清白蛋白、血肌酐水平比較無統(tǒng)計學(xué)差異(P>0.05);治療后兩組尿蛋白水平顯著降低,血清白蛋白顯著升高,差異有統(tǒng)計學(xué)意義(P<0.05);且觀察組患者治療后尿蛋白水平顯著低于對照組,血清白蛋白顯著高于對照組,兩組組間比較,差異有統(tǒng)計學(xué)意義(P<0.05),但兩組患者血肌酐水平治療前后以及組間比較未見明顯差異(P>0.05)。
2.3 不良反應(yīng)
兩組患者治療期間未見明顯不良反應(yīng)。
3 討論
特發(fā)性膜性腎病約占膜性腎病的 2/3,臨床上約 80%的特發(fā)性膜性腎病患者表現(xiàn)為腎病綜合征,超過40%的特發(fā)性膜性腎病患者可進(jìn)展至終末期腎病[8-15]。
目前國內(nèi)對存在大量蛋白尿的膜性腎病患者的傳統(tǒng)標(biāo)準(zhǔn)治療方案是糖皮質(zhì)激素聯(lián)合環(huán)磷酰胺(cyclophosphamide,CTX)沖擊治療,但 CTX副作用較多,嚴(yán)重影響患者疾病的預(yù)后。
糖皮質(zhì)激素為治療腎病綜合征的常用藥物,但研究顯示,無論是短期還是長期,單用激素均不能緩解特發(fā)性膜性腎病患者的尿蛋白水平,也不能降低患者進(jìn)入終末期腎病的風(fēng)險,故不推薦單獨應(yīng)用[16-23]。他克莫司為新型免疫抑制藥,可較好地調(diào)節(jié)患者的免疫功能,抑制 T 細(xì)胞激活、增殖及具有免疫放大效應(yīng)的作用,且不良反應(yīng)較少,目前廣泛應(yīng)用于器官移植和自身免疫性疾病的治療[24-26]。臨床許多研究也證實,他克莫司可減少蛋白尿,提升血漿白蛋白指數(shù),有效恢復(fù)患者實驗室指標(biāo),控制患者蛋白尿水平[27-28]。劉國建等[29]將53例經(jīng)腎穿刺活檢術(shù)后確診的特發(fā)性膜性腎病患者分為他克莫司組(A組)和環(huán)磷酰胺組(B組),治療后,他克莫司組與環(huán)磷酰胺組患者治療后血清白蛋白明顯上升,24 h尿蛋白定量明顯下降,但他克莫司組較環(huán)磷酰胺組變化更顯著,差異具有統(tǒng)計學(xué)意義(P<0.05),證實他克莫司聯(lián)合糖皮質(zhì)激素治療特發(fā)性膜性腎病療效好,且短期療效可能優(yōu)于環(huán)磷酰胺。本研究結(jié)果也證實了上述觀點,觀察組治療后的總緩解率(95.00%)顯著高于對照組的70.00%,差異具有統(tǒng)計學(xué)意義(P<0.05)。且觀察組患者治療后尿蛋白水平顯著低于對照組,血清白蛋白顯著高于對照組,差異具有統(tǒng)計學(xué)意義(P<0.05),與楊瑞衡等[30]報道的觀點是相符的,說明他克莫司聯(lián)合糖皮質(zhì)激素治療特發(fā)性膜性腎病療效顯著,可以顯著改善腎功能,值得推廣和應(yīng)用。
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(收稿日期:2016-11-06)