范佳妮 林明增 陳璐
[摘要] 目的 探討西那卡塞聯(lián)合骨化三醇對(duì)血液透析繼發(fā)性甲狀旁腺功能亢進(jìn)患者的療效。 方法 選取2017年1月~2019年1月在我院行血液透析繼發(fā)性甲狀旁腺功能亢進(jìn)患者64例,隨機(jī)分為觀察組與對(duì)照組各32例。兩組患者繼續(xù)予以維持性透析治療,對(duì)照組予以骨化三醇治療,觀察組在此治療基礎(chǔ)上加西那卡塞治療。兩組均連用3個(gè)月,檢測兩組治療前后血清鈣、血清磷、全段甲狀旁腺激素水平及甲狀旁腺體積,并評(píng)估其臨床療效及不良反應(yīng)。 結(jié)果 治療3個(gè)月后兩組血清磷與全段甲狀旁腺激素水平均較前明顯下降,血清鈣水平均較前明顯升高(P<0.05或P<0.01),且觀察組變化幅度較對(duì)照組更顯著(P<0.05);兩組甲狀旁腺長、寬、厚及體積均較前明顯下降(P<0.05或P<0.01),且觀察組下降幅度較對(duì)照組更顯著(P<0.05)。觀察組臨床治療總有效率明顯高于對(duì)照組(χ2=4.272,P<0.05)。觀察組和對(duì)照組不良反應(yīng)發(fā)生率分別為12.50%(4/32)和6.25%(2/32),癥狀均較輕,兩組比較差異無統(tǒng)計(jì)學(xué)意義(χ2=0.180,P>0.05)。 結(jié)論 西那卡塞聯(lián)合骨化三醇治療血液透析繼發(fā)性甲狀旁腺功能亢進(jìn)患者的臨床效果確切,安全性較好,能明顯降低甲狀旁腺激素水平及甲狀旁腺體積,改善鈣磷代謝紊亂。
[關(guān)鍵詞] 血液透析患者繼發(fā)性甲狀旁腺功能亢進(jìn);骨化三醇;西那卡塞;全段甲狀旁腺激素
[中圖分類號(hào)] R459.5 ? ? ? ? ?[文獻(xiàn)標(biāo)識(shí)碼] B ? ? ? ? ?[文章編號(hào)] 1673-9701(2020)24-0116-04
[Abstract] Objective To explore the efficacy of cinacalcet combined with calcitriol on patients with secondary hyperparathyroidism during hemodialysis. Methods 64 patients with secondary hyperparathyroidism who underwent hemodialysis in our hospital from January 2017 to January 2019 were randomly divided into the observation group and the control group, with 32 cases in each group. Both groups continued to undergo maintenance dialysis, while the control group was treated with calcitriol, and the observation group was treated with cinacalcet on the basis of this treatment. Both groups were treated continuously for 3 months. Serum calcium, serum phosphorus, whole parathyroid hormone levels and parathyroid volume were measured before and after treatment in both groups, and their clinical efficacy and adverse reactions were evaluated. Results After 3 months of treatment, the levels of serum phosphorus and whole parathyroid hormone in the two groups were significantly lower than those before treatment. Serum calcium level was significantly higher than that before treatment(P<0.05 or P<0.01), and the change in the observation group was more significant than that in the control group(P<0.05); the length, width, thickness and volume of parathyroid glands in the two groups were significantly lower than those before treatment(P<0.05 or P<0.01), and the decline in the observation group was more significant than that in the control group(P<0.05). The total effective rate of clinical treatment in the observation group was significantly higher than that in the control group(χ2=4.272, P<0.05). The incidences of adverse reactions in the observation group and the control group were 12.50%(4/32) and 6.25% (2/32), respectively, and the symptoms were both mild, and the differences were not statistically significant(χ2=0.180, P>0.05). Conclusion The clinical effect of cinacalcet combined with calcitriol in the treatment of patients with secondary hyperparathyroidism during hemodialysis is definite and safe. It can significantly reduce parathyroid hormone levels and parathyroid volume, and improve calcium and phosphorus metabolism disorders.
[Key words] Secondary hyperparathyroidism in hemodialysis patients; Calcitriol; Cinacalcet; Full-parathyroid hormone
血液透析是治療慢性腎臟疾病終末期的首選治療方案,但長期透析可能導(dǎo)致出現(xiàn)一系列并發(fā)癥,其中繼發(fā)性甲狀旁腺功能亢進(jìn)較常見[1-3]。繼發(fā)性甲狀旁腺功能亢進(jìn)一旦出現(xiàn),如不及時(shí)干預(yù)治療,會(huì)增加患者的心血管風(fēng)險(xiǎn),死亡率較高[4]。西那卡塞是一種鈣受體激動(dòng)劑,可以抑制甲狀旁腺的增生,減少全段甲狀旁腺激素的分泌,改善血清鈣及血清磷的水平,達(dá)到“可逆性化學(xué)切除甲狀旁腺”的目的[5]。骨化三醇是活性最強(qiáng)的1,25-二羥代謝物,能促進(jìn)腸道鈣的吸收和形成新的成骨細(xì)胞,從而促使骨的吸收,但骨化三醇與西那卡塞聯(lián)合用于血液透析患者繼發(fā)性甲狀旁腺功能亢進(jìn)國內(nèi)報(bào)道較少[6]。本研究觀察了西那卡塞聯(lián)合骨化三醇對(duì)血液透析患者繼發(fā)性甲狀旁腺功能亢進(jìn)的療效,現(xiàn)報(bào)道如下。
1 資料與方法
1.1 一般資料
選取2017年1月~2019年1月在我院就診的血液透析繼發(fā)性甲狀旁腺功能亢進(jìn)患者共64例。納入標(biāo)準(zhǔn)[7]:(1)透析齡>6個(gè)月,透析頻率3次/周;(2)全段甲狀旁腺激素水平>7.3 pmol/L,且經(jīng)超聲檢查發(fā)現(xiàn)甲狀旁腺無結(jié)節(jié)形成,符合中華醫(yī)學(xué)會(huì)腎臟病學(xué)分會(huì)制定的繼發(fā)性甲狀旁腺功能亢進(jìn)的診斷標(biāo)準(zhǔn)[8]。排除標(biāo)準(zhǔn)[9]:(1)2周內(nèi)未使用維生素D制劑或影響骨代謝的藥物;(2)預(yù)期壽命<6個(gè)月;(3)伴有嚴(yán)重的心腦血管并發(fā)癥。采用隨機(jī)數(shù)字表法分為觀察組和對(duì)照組各32例,兩組性別、年齡、透析時(shí)間、原發(fā)病類型等比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05),具有可比性。見表1。
1.2 方法
兩組患者繼續(xù)予以維持性透析治療(采用德國費(fèi)森尤斯透析機(jī),聚砜膜透析器,面積1.5 m2,透析液Ca2+濃度為1.5 mmol/L,血流量200~260 mL/min,應(yīng)用低分子肝素抗凝,超濾量設(shè)定為5%,透析3次/周,單次時(shí)間4 h)。對(duì)照組予以骨化三醇注射液(Abbott Laboratories Limited,規(guī)格:1 mL/1 μg)(0.5~1)μg/次,全段甲狀旁腺激素水平600~1000 pg/mL時(shí),骨化三醇注射液1 μg/次,全段甲狀旁腺激素水平>1000 pg/mL時(shí),骨化三醇注射液(1~1.5)μg/次。觀察組在此治療的基礎(chǔ)上加用鹽酸西那卡塞片(協(xié)和發(fā)酵麒麟制藥有限公司,規(guī)格:25 mg),初始劑量25 mg/d,根據(jù)血鈣水平調(diào)節(jié)用量,血鈣>2.1 mmol/L,增加藥物劑量25 mg/d;血鈣1.9~2.1 mmol/L,維持原藥物劑量;血鈣<1.9 mmol/L,停藥補(bǔ)鈣至2.1 mmol/L再給藥,最大劑量75 mg/d。兩組均連用3個(gè)月,檢測兩組治療前后血清鈣、血清磷、全段甲狀旁腺激素水平及甲狀旁腺體積,并評(píng)估其臨床療效及不良反應(yīng)。
1.3 觀察指標(biāo)
1.3.1 血清鈣、磷及全段甲狀旁腺激素水平檢測 ?取空腹靜脈血約3~5 mL,3000 r/min離心10 min取血清。采用酶聯(lián)免疫吸附法(ELISA)檢測血清鈣、血清磷及全段甲狀旁腺激素水平,試劑盒由北京榮志海達(dá)生物科技有限公司提供。
1.3.2 甲狀旁腺體積測量 ?彩色多普勒超聲儀器使用Vivid9超聲診斷儀器(美國GE公司),檢測甲狀旁腺厚度、寬度和長度,計(jì)算其體積。
1.3.3 療效評(píng)價(jià)[10] ?顯效:治療后甲狀旁腺激素水平下降≥75%;有效:治療后甲狀腺旁腺激素水平下降≥25%且<75%;無效:治療后甲狀旁腺激素水平下降<25%或出現(xiàn)升高。總有效包括顯效和有效。
1.3.4 不良反應(yīng) ?觀察患者治療期間出現(xiàn)的與藥物有關(guān)的不良事件,包括胃腸道反應(yīng)、肌肉疼痛和血壓升高等。
1.4 統(tǒng)計(jì)學(xué)處理
應(yīng)用SPSS19.0統(tǒng)計(jì)學(xué)軟件進(jìn)行分析,計(jì)量資料以(x±s)表示,采用t檢驗(yàn);計(jì)數(shù)資料以[n(%)]表示,采用χ2檢驗(yàn),P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 兩組治療前后血清鈣、血清磷及全段甲狀旁腺激素水平比較
治療前兩組血清鈣、血清磷及全段甲狀旁腺激素水平比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。治療3個(gè)月后兩組血清磷與全段甲狀旁腺激素水平均較前明顯下降,血清鈣水平均較前明顯升高(P<0.05或P<0.01),且觀察組變化幅度較對(duì)照組更顯著(P<0.05)。見表2。
2.2 兩組治療前后甲狀旁腺體積比較
治療前兩組甲狀旁腺長、寬、厚及體積比較,差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。治療3個(gè)月后兩組甲狀旁腺長、寬、厚及體積均較前明顯下降(P<0.05或P<0.01),且觀察組下降幅度較對(duì)照組更顯著(P<0.05)。見表3。
2.3 兩組治療后療效比較
治療3個(gè)月后觀察組臨床治療總有效率明顯高于對(duì)照組(χ2=4.272,P<0.05)。見表4。
2.4 兩組不良反應(yīng)比較
治療期間觀察組不良反應(yīng)發(fā)生率為12.50%(4/32),其中胃腸道反應(yīng)2例、肌肉疼痛和血壓升高各1例;對(duì)照組發(fā)生率為6.25%(2/32),其中胃腸道反應(yīng)和肌肉疼痛各1例。上述癥狀均較輕,未影響患者繼續(xù)用藥。兩組不良反應(yīng)發(fā)生率比較,差異無統(tǒng)計(jì)學(xué)意義(χ2=0.180,P>0.05)。
3 討論
近年來,隨著糖尿病和高血壓等基礎(chǔ)疾病發(fā)病率的增加,慢性腎病患者逐年增多,慢性腎病終末期常需要透析治療[10]。繼發(fā)性甲狀旁腺功能亢進(jìn)是維持性血液透析最常見的并發(fā)癥之一,有研究顯示約70%的慢性腎病晚期患者會(huì)出現(xiàn)繼發(fā)性的甲狀旁腺功能亢進(jìn)[11]。這是由于維持性血液透析患者常處于高磷、低鈣、低維生素D活性的狀態(tài),而此類患者鈣磷代謝的紊亂和甲狀旁腺激素抵抗的增加會(huì)刺激甲狀旁腺亢進(jìn)、增生,導(dǎo)致繼發(fā)性甲狀旁腺功能亢進(jìn)的發(fā)生。患者一旦出現(xiàn)甲狀旁腺功能亢進(jìn)會(huì)造成體內(nèi)電解質(zhì)紊亂、骨骼損害及心腦血管鈣化等多系統(tǒng)損害疾病,患者會(huì)出現(xiàn)貧血、皮膚瘙癢和神經(jīng)系統(tǒng)損害等臨床癥狀,嚴(yán)重者會(huì)危及患者生命[12-14]。
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(收稿日期:2019-09-24)