李朝軍 李 凡 秦 燕 張 茜 高 峰 杜聯(lián)芳 羅向紅△

(1上海交通大學(xué)附屬第一人民醫(yī)院超聲科,2泌尿科,3心超室 上海 200080)

腎移植后頸總動(dòng)脈形態(tài)及其衰老進(jìn)程

李朝軍1李 凡1秦 燕2張 茜3高 峰1杜聯(lián)芳1羅向紅3△

(1上海交通大學(xué)附屬第一人民醫(yī)院超聲科,2泌尿科,3心超室 上海 200080)

目的 分析腎移植患者頸總動(dòng)脈形態(tài)學(xué)參數(shù)隨年齡變化的斜率,探討其衰老進(jìn)程。方法 31例腎移植患者(kidney transplant recipient,KTR),31例維持性血透的終末期腎病(end-stage renal disease,ESRD)患者,84例年齡、性別匹配的對(duì)照接受頸動(dòng)脈超聲檢查。測(cè)量右頸總動(dòng)脈內(nèi)-中膜厚度(carotid intima-media thickness,CIMT)和右頸總動(dòng)脈管徑(common carotid artery diameter,CCAD)。CIMT和CCAD隨年齡變化的斜率采用線性回歸分析。結(jié)果 ESRD組患者與KTR組和對(duì)照組比較,CIMT增厚,CCAD增寬(P<0.05)。KTR組和對(duì)照組之間CIMT和CCAD差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。CIMT與年齡呈正相關(guān)(P<0.05)。CIMT隨年齡變化的斜率(回歸系數(shù)b):對(duì)照組大于KTR組和ESRD組(Z=1.417,P=0.006;Z=2.223,P<0.001),KTR組和ESRD組之間的差異無統(tǒng)計(jì)學(xué)意義(Z=1.038,P=0.723)。CCAD與年齡呈正相關(guān)(P<0.05)。CCAD隨年齡變化的斜率:ESRD組小于對(duì)照組(Z=1.677,P=0.002)。結(jié)論 腎移植患者頸總動(dòng)脈形態(tài)學(xué)部分改善,血管衰老逐步恢復(fù)自然進(jìn)程。

腎移植; 終末期腎病; 頸總動(dòng)脈; 形態(tài)學(xué); 衰老; 超聲

維持性血透的終末期腎病(end-stage renal disease,ESRD)患者中急性冠脈綜合征和心血管致死事件的發(fā)生率都很高[1]。同種異體腎移植可降低血液透析患者心血管事件的發(fā)生率[2]。新近發(fā)現(xiàn),同種異體腎移植的ESRD患者頸總動(dòng)脈內(nèi)膜和中膜厚度(carotid intima-media thickness,CIMT)變薄,動(dòng)脈僵硬度部分恢復(fù)[3]。動(dòng)脈結(jié)構(gòu)和功能不僅與年齡密切相關(guān),而且與年齡的線性回歸系數(shù)可反映動(dòng)脈的衰老進(jìn)程[4]。觀察維持性血透的ESRD患者,在腎移植前后動(dòng)脈結(jié)構(gòu)和衰老進(jìn)程的變化,可提高對(duì)腎移植(kidney transplant recipient,KTR)患者心血管變化的認(rèn)識(shí),也可預(yù)警心血管事件的發(fā)生。本研究運(yùn)用精度達(dá)微米級(jí)的超聲射頻技術(shù)檢測(cè)腎移植患者頸總動(dòng)脈結(jié)構(gòu)參數(shù),評(píng)估動(dòng)脈形態(tài)學(xué)變化以及衰老進(jìn)程。

資 料 和 方 法

研究對(duì)象 選擇2014年3月至2015年12月于上海交通大學(xué)附屬第一人民醫(yī)院泌尿外科接受KTR的成年患者55例及每周2～3次維持透析的ESRD患者63例。依據(jù)研究目的,排除標(biāo)準(zhǔn):糖尿病、腹膜透析、未治療的心臟疾病或高脂血癥、腦梗死、惡性腫瘤、慢性肝炎和活動(dòng)性感染等。最終入選腎移植組31例和血液透析組31例。移植組患者,男20例,女11例,年齡25～70歲,平均(47.9±14.3)歲。所有腎移植患者均接受常規(guī)免疫抑制治療。腎移植患者術(shù)前血液透析累積時(shí)間3～65個(gè)月,術(shù)后隨訪1～22個(gè)月。血液透析組患者,男22例,女9例,年齡27～68歲,平均(50.3±17.9)歲,維持性血透的ESRD患者與腎移植患者術(shù)前累積血液透析持續(xù)時(shí)間匹配。按年齡、性別以1∶2或1∶3進(jìn)行匹配,篩選84例受試者為對(duì)照組,男55例,女29例,年齡22～74 歲,平均(43.1±19.9)歲。受試者尿常規(guī)、腎功能正常,無心腦血管事件,無肝病及結(jié)締組織病活動(dòng)期。所有研究對(duì)象檢查當(dāng)天停服降壓藥,24 h內(nèi)禁止吸煙、飲酒或咖啡等。研究經(jīng)本院倫理委員會(huì)同意,所有受試者均簽署知情同意書。

儀器和方法 采用百勝M(fèi)ylab Twice彩色多普勒超聲診斷儀,探頭LA523,頻率4～13 MHz。內(nèi)置超聲射頻技術(shù)(quality intima-media thickness,QIMT)分析軟件。頸總動(dòng)脈結(jié)構(gòu)及血流動(dòng)力學(xué)檢查:依據(jù)我們前期研究的結(jié)果和方法[5],分別獲取CIMT和右頸總動(dòng)脈管徑(common carotid arterial diameter,CCAD)。

收集患者一般資料及病史信息。高血壓診斷依據(jù)《高血壓防治指南2005年修訂版》;糖尿病診斷依據(jù)1999年WHO診斷標(biāo)準(zhǔn):任意血糖≥11.1μmol/L或空腹血糖≥7.0μmol/L。受檢者均在清晨空腹?fàn)顟B(tài)下靜脈采血,檢測(cè)空腹血糖(fasting plasma glucose,FPG)、三酰甘油(triglyceride,TG)、總膽固醇(total cholesterol,TC)、低密度脂蛋白膽固醇(low-density lipoprotein cholesterol,LDL)、血鈣(calcium,Ca)、血磷(phosphorus,P)。平靜狀態(tài)下測(cè)量左側(cè)肱動(dòng)脈收縮壓(systolic blood pressure,SBP)和舒張壓(diastolic blood pressure,DBP),3次取平均值。

結(jié) 果

一般資料比較 年齡和身高在3組間差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。ESRD組和KTR組患者SBP和DBP均高于對(duì)照組(P<0.05)。SBP和DBP在ESRD組和KTR組間差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。KTR組患者BMI和身高均低于ESRD組和對(duì)照組(P<0.05)。TC、TG、LDL和FPG在3組間差異無統(tǒng)計(jì)學(xué)意義(P>0.05)。ESRD組患者血磷高于KTR組和對(duì)照(P<0.05)(表1)。

頸總動(dòng)脈結(jié)構(gòu)參數(shù)比較ESRD組患者CIMT較KTR組和對(duì)照組厚(P<0.05)。KTR組與對(duì)照組之間CIMT的差異無統(tǒng)計(jì)學(xué)意義。ESRD組患者頸總動(dòng)脈內(nèi)徑較對(duì)照組和KTR組增寬(P<0.05)。頸總動(dòng)脈內(nèi)徑在KTR組和對(duì)照組之間CCAD的差異無統(tǒng)計(jì)學(xué)意義(表1)。

表1 一般資料和頸總動(dòng)脈結(jié)構(gòu)參數(shù)比較

vs.Control,(1)P<0.05,(2)P<0.01;vs. ESRD,(3)P<0.05,(4)P<0.01.BMI:Body mass index;FPG:Fasting plasma glucose;TC:Total cholesterol;TG:Triglycerides;HDL:High-density lipoprotein;LDL:Low-density lipoprotein;SBP:Systolic blood pressure;DBP:Diastolic blood pressure;CIMT:Carotid intima-media thickness;CCAD:Common carotid arterial diameter.1 mm Hg =0.133 kPa.

CIMT和CCAD的相關(guān)影響因子分析 年齡、體重、BMI和SBP與CIMT呈正相關(guān)(r=0.544、0.272、0.312和0.212,P均<0.05)。年齡、體重、BMI和SBP與CCAD呈正相關(guān)(r=0.678、0.275、0.315和0.274,P均<0.05)。CIMT隨年齡變化的斜率(回歸系數(shù)b)在對(duì)照組、KTR組和ESRD組呈下降趨勢(shì)(表2)。對(duì)照組斜率大于KTR組和ESRD組(Z=1.417,P=0.006;Z=2.223,P<0.001),但KTR組和CKD組之間差異無統(tǒng)計(jì)學(xué)意義(Z=1.038,P=0.723)(圖1)。ESRD組CCAD隨年齡變化的斜率較對(duì)照組小(Z=1.677,P=0.002)。KTR組CCAD隨年齡變化的斜率介于對(duì)照組和ESRD組之間,差異無統(tǒng)計(jì)學(xué)意義(Z=1.693,P=0.911;Z=0.372,P=0.416)(表3,圖2)。

討 論

血管衰老(或稱動(dòng)脈生理性硬化)概念尚不明確,一般認(rèn)為是指隨著年齡增加,血管管腔擴(kuò)大、迂曲延長(zhǎng)、CIMT等[6]。與以局限性內(nèi)膜改變?yōu)樘卣鞯牟±硇詣?dòng)脈粥樣硬化不同,動(dòng)脈衰老不僅內(nèi)膜改變,而且更主要的是中層彌漫性的增厚退化、管壁硬化及管腔擴(kuò)大[7]。因此,通過觀察血管管徑和IMT隨年齡變化的斜率可反映血管衰老的進(jìn)程。本研究發(fā)現(xiàn),CIMT隨年齡變化的斜率在對(duì)照組、KTR組和ESRD組呈下降趨勢(shì);而CCAD隨年齡變化的斜率在腎移植組最大,在ESRD組最小。提示維持血透的ESRD患者在腎移植后,血管衰老進(jìn)程減緩或恢復(fù)正常生理進(jìn)程。

表2 CIMT與年齡線性回歸分析結(jié)果

表3 CCAD與年齡線性回歸分析結(jié)果

Control groupvs. ESRD group,Z=2.223,P<0.001;ESRD groupvs. KTR group,Z=1.038,P=0.723;KTR groupvs.Control group,Z=1.417,P=0.006.

圖1 CIMT與年齡線性回歸分析

Fig 1 Linear regression analysis of CIMT with age

CIMT>1.1 mm即定義為斑塊,故CIMT的極值為1.1 mm[8]。因此,CIMT隨年齡變化的斜率越小,提示年齡越小CIMT增厚的越明顯,血管衰老進(jìn)程越早。本研究發(fā)現(xiàn),維持性血透ESRD患者CIMT增厚,KTR患者術(shù)后CIMT逐漸變薄。de Lima等[9]隨訪22例成人腎移植患者3年,發(fā)現(xiàn)CIMT變薄,其結(jié)果與本研究相似。Suwelack等[10]的研究也支持該結(jié)果,CIMT與血壓降低密切相關(guān)。維持血透的ESRD患者常伴有鈣磷紊亂、營(yíng)養(yǎng)不良、脂質(zhì)代謝異常、炎性反應(yīng)等血管危險(xiǎn)因素。同種異體腎移植后可有效改善患者部分危險(xiǎn)因素使血管結(jié)構(gòu)部分恢復(fù)。CIMT和CCAD是動(dòng)脈結(jié)構(gòu)重構(gòu)、硬化程度和衰老的重要指標(biāo),是公認(rèn)的預(yù)測(cè)心血管事件和死亡率的強(qiáng)的、獨(dú)立的指標(biāo)。鑒于血管衰老是一種自然進(jìn)程,因此腎移植后患者CIMT和CCAD不會(huì)持續(xù)變薄和減小。為證明該假設(shè),本研究采用CIMT和CCAD與年齡線性回歸斜率評(píng)價(jià)血管衰老進(jìn)程。結(jié)果發(fā)現(xiàn),持續(xù)性血透患者血管衰老進(jìn)程加快,而腎移植后患者血管衰老進(jìn)程逐步恢復(fù)至自然進(jìn)程。有研究發(fā)現(xiàn),維持性血透患者5年死亡率較高,其中半數(shù)死于心血管疾病[11]。最新流行病學(xué)研究顯示[12],維持血透患者存在一種“逆流行病學(xué)(reverse epidemiology)”現(xiàn)象,主要表現(xiàn)為高血壓、高膽固醇血癥、高體質(zhì)指數(shù)等,反而具有更高生存優(yōu)勢(shì)。分析原因:一方面,與血透初期殘腎功能下降過快、鈣磷脂質(zhì)代謝紊亂、慢性炎性反應(yīng)等因素有關(guān)[13];另一方面,動(dòng)靜脈“透析瘺管”的存在改變了心血管系統(tǒng)的血流動(dòng)力學(xué),加重循環(huán)系統(tǒng)負(fù)荷,導(dǎo)致動(dòng)脈僵硬度增加,心臟后負(fù)荷加重。另外,維持血透患者營(yíng)養(yǎng)不良、貧血致心肌缺血、動(dòng)脈硬化、鈣磷脂質(zhì)代謝紊亂,進(jìn)一步加速動(dòng)脈硬化、加重心肌負(fù)荷,最終導(dǎo)致心血管事件的發(fā)生[14]。因此,同種異體腎臟移植成功后不僅改善了血透患者的生活質(zhì)量,而且通過抑制炎癥、恢復(fù)鈣磷代謝、改善營(yíng)養(yǎng)、消除腎衰源性等多個(gè)途徑,降低了患者發(fā)生心血管事件的危險(xiǎn)因素,部分改善和恢復(fù)了患者的大動(dòng)脈形態(tài)學(xué)結(jié)構(gòu)。

Control groupvs. ESRD group,Z=1.677,P=0.002;ESRD groupvs. KTR group,Z=1.693,P=0.911;KTR groupvs. Control group,Z=0.372,P=0.416.

圖2 CCAD與年齡線性回歸分析

Fig 2 Linear regression analysis of CIMT with age

對(duì)于腎移植患者CIMT如何變化還存在一定的爭(zhēng)議。Nafar等[15]連續(xù)隨訪26例腎移植患者6個(gè)月,發(fā)現(xiàn)腎移植患者CIMT增厚。Mitsnefes等[16]觀察332例腎移植兒童患者,隨訪時(shí)間小于1年,發(fā)現(xiàn)CIMT較移植前更厚,且與SBP密切相關(guān)。分析原因:一方面可能跟腎移植后隨訪時(shí)間較短,CIMT的增厚存在一定“慣性”;另一方面可能和IMT檢測(cè)技術(shù)的精度有關(guān)。為盡可能消除干擾因素,降低腎移植患者術(shù)前維持性血透對(duì)結(jié)果的影響,本研究篩選ESRD組患者的累積透析時(shí)間與KTR組相匹配。為減小CIMT測(cè)量誤差,提高檢測(cè)精度,本研究采用一種較新的的方法——超聲射頻技術(shù)。該技術(shù)是基于超聲射頻信號(hào)分析,檢測(cè)一段(1～1.5 cm)頸總動(dòng)脈上30～50個(gè)取樣點(diǎn)的CIMT,隨后獲得其平均值記為1次CIMT,連續(xù)測(cè)量6次再取平均值來確定最終的CIMT厚度。該方法不僅測(cè)量精度可達(dá)微米,而且重復(fù)性更高[17]。結(jié)果發(fā)現(xiàn)ESRD患者CIMT增厚,CCAD增寬;KTR患者CIMT減低,CCAD縮小。提示KTR患者頸總動(dòng)脈形態(tài)學(xué)結(jié)構(gòu)可部分恢復(fù),這與de Lima等[9]和Suwelack等[10]的研究結(jié)果一致。進(jìn)一步分析發(fā)現(xiàn),年齡、體重、BMI、血壓及部分血流動(dòng)力學(xué)參數(shù)是CIMT和CCAD的獨(dú)立危險(xiǎn)因素。提示腎移植較持續(xù)性血透更有利于ESRD患者降低心血管危險(xiǎn)因素,減少心血管事件的發(fā)生。

本研究的局限性在于:樣本量較小;實(shí)驗(yàn)室設(shè)計(jì)未采取腎移植前后進(jìn)行對(duì)照或移植后長(zhǎng)期隨訪研究,使本研究的論證強(qiáng)度受到一定的影響;CIMT和CCAD相關(guān)的影響因素較多,與原發(fā)病、藥物的應(yīng)用、透析患者透析齡等均相關(guān)。本研究通過CIMT和CCAD與年齡的線性關(guān)系的變化,反證腎移植后患者除年齡以外血管危險(xiǎn)因素對(duì)頸動(dòng)脈衰老進(jìn)程影響總權(quán)重的變化,尚不能完全解釋腎移植后患者動(dòng)脈衰老是如何恢復(fù)自然進(jìn)程,有待于進(jìn)一步分層分析深入研究。另外,自然人群中雙側(cè)頸總動(dòng)脈結(jié)構(gòu)和功能存在差異,且動(dòng)脈功能學(xué)參數(shù)較形態(tài)學(xué)參數(shù)變化更早[18]。這些關(guān)系在腎移植前后是否存在或如何變化都有待于進(jìn)一步研究。

綜上所述,維持性血透的ESRD患者CIMT增厚、CCAD增寬。腎移植后,受者CIMT變薄,CCAD縮窄。這一發(fā)現(xiàn)對(duì)于持續(xù)性血液透析的ESRD患者具有重要的臨床意義,提示腎移植成功后,不僅可以改善受者的生活質(zhì)量,而且可部分改善甚至逆轉(zhuǎn)患者受損的動(dòng)脈,并逐步恢復(fù)其血管衰老的自然進(jìn)程。本研究結(jié)果也支持對(duì)腎移植患者術(shù)后行CIMT和CCAD常規(guī)隨訪、檢測(cè)和評(píng)估,對(duì)于CIMT和CCAD改善不明顯的腎移植患者需要進(jìn)行心血管危險(xiǎn)因素的再評(píng)估,明確是否存在新增的危險(xiǎn)因素,以防止腎移植患者心腦血管事件的發(fā)生。

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Morphologic properties and aging process of common carotid artery after kidney transplantation

LI Zhao-jun1, LI Fan1, QIN Yan2, ZHANG Qian3, GAO Feng1, DU Lian-fang1, LUO Xiang-hong3△

(1DepartmentofUltrasound,2DepartmentofUrology,3DepartmentofEchocardiography,ShanghaiGeneralHospital,ShanghaiJiaoTongUniversity,Shanghai200080,China)

Objective To study the change rules with age in morphologic properties of common carotid artery,and to discuss its aging process after kidney transplantation. Methods Thirty-one patients with end-stage renal disease (ESRD) supported by hemodialysis,31 kidney transplant recipients (KTR) and 84 control subjects were offered an ultrasound of carotid artery.The carotid intima-media thickness (CIMT) and common carotid artery diameter (CCAD) of right carotid arteries were measured by ultrasonic frequency tracking.The tends for slope of CIMT and CCAD with age were analyzed by linear regression analysis. Results Compared with KTR group and control group,ESRD group had significantly thicker CIMT and wider CCAD,but there was no significant difference between KTR group and control group.The linear regression showed the development of CIMT were positively associated with age (P<0.05).Compared with KTR group and ESRD group respectively,the slope of

CIMT with age (unstandardized coefficients b) in control group was greater (Z=1.417,P=0.006;Z=2.223,P<0.001).There was no significant difference between KTR group and ESRD group (Z=1.038,P=0.723).The development of CCAD were also positively associated with age (P<0.05).Compared with control group,the slope of CCAD with age in ESRD group was less (Z=1.677,P=0.002). Conclusions After successful kidney transplantation,some morphologic properties of carotid artery are improved and resume the normal aging process.

kidney transplantation; end-stage renal disease; common carotid artery; morphology; aging; ultrasound

R445.1，R692.5

A

10.3969/j.issn.1672-8467.2017.03.002

2016-06-29;編輯:段佳)

上海市科學(xué)技術(shù)委員會(huì)醫(yī)學(xué)引導(dǎo)類科技項(xiàng)目(15411969100,16411969300);上海市衛(wèi)生和計(jì)劃生育委員會(huì)基金(201440290,201640043);上海交通大學(xué)醫(yī)工交叉研究基金(YG2015MS28)

△Corresponding author E-mail:lxh_20050703@sina.com

*This work was supported by the Medical Induction Project from Science and Technology of Shanghai Municipality (15411969100,16411969300),the Fund from Shanghai Municipal Commission of Health and Family Planning (201440290,201640043) and the Interdisciplinary Project of Medicine and Engineering from Shanghai Jiao Tong University (YG2015MS28).