本文選題：糖尿病腎病 + 腎功能　； 參考：《第三軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：背景與目的:根據(jù)國際糖尿病聯(lián)盟(international diabetes federation,IDF)最新數(shù)據(jù),糖尿病(diabetes mellitus,DM)已經(jīng)發(fā)展成為全球性的慢性疾病,2015年全球DM患者達(dá)到4.15億,其中中國患病人數(shù)達(dá)到1.09億。由于腎臟是DM的重要靶點器官,40%的患者將發(fā)展為糖尿病腎病(diabetic kidney disease,DKD),DKD是糖尿病常見的并發(fā)癥之一,是目前引起終末期腎病(end-stage renal disease,ESRD)的首要原因。既往的病理生理學(xué)研究發(fā)現(xiàn),糖尿病病情演變過程中,腎臟功能受損主要集中于灌注及氧合水平、水分子彌散運動三個方面。糖尿病早期主要是腎臟皮質(zhì)灌注受累,高血糖作用于腎臟微小血管,激活腎臟代償機制,使得腎臟的血流供應(yīng)和腎功能增強,直至代償消失。同時腎臟氧合水平也呈現(xiàn)出先升高再降低的變化,這與血流灌注基本一直。當(dāng)病情進(jìn)展至皮、髓質(zhì)結(jié)構(gòu)增生甚至纖維化時,集合系統(tǒng)內(nèi)水分子彌散運動也將受到限制,如不進(jìn)行及時的治療,最終進(jìn)展為ESRD。因腎臟具有強大的代償能力,糖尿病早期腎臟各項指標(biāo)仍在正常范圍內(nèi),導(dǎo)致患者就診時多已進(jìn)展至DKD晚期,錯過了最佳治療時間,因此需要我們盡量早期發(fā)現(xiàn)、早期診斷。目前臨床使用的常規(guī)檢查多有創(chuàng)或需要使用外源性對比劑,且不能夠早期發(fā)現(xiàn)異常改變,并且既往對DKD研究多局限于灌注或氧合水平某一方面的改變,缺乏對腎臟功能進(jìn)行整體、全面的分析。只有充分了解病情演變過程的前提下,才能夠?qū)KD有新的認(rèn)識,做到早期發(fā)現(xiàn)、早期診斷。因此迫切一種需要簡單易行的方式,能夠從灌注到氧合水平和水分子運動變化的角度,觀察糖尿病狀態(tài)下腎臟的變化過程,并對腎臟功能進(jìn)行全面的評估。隨著影像學(xué)技術(shù)的進(jìn)步,出現(xiàn)了很多新的技術(shù)方法,如動脈自旋標(biāo)記(arterial spin labeling,ASL)、血氧水平依賴(blood oxygenation level dependent,BOLD)、彌散張量成像(diffusion tensor imaging,DTI)等功能磁共振(functional magnetic resonance imaging,fMRI)技術(shù),給我們解決上述臨床遇到的困境,提供了可靠、無創(chuàng)的技術(shù)手段。本研究以這些技術(shù)為抓手,根據(jù)病情發(fā)展演變規(guī)律,對比、觀察腎臟灌注、氧合水平、水分子彌散運動三個方面的改變,并對腎功能進(jìn)行影像學(xué)評價,尋找他們之間的聯(lián)系,探討DKD發(fā)展的病理生理機制,為早期發(fā)現(xiàn)DKD提供理論支持。材料與方法:1、動脈自旋標(biāo)記MRI評估糖尿病腎皮質(zhì)灌注水平的研究納入50名Ⅱ型糖尿病患者,根據(jù)美國腎臟病基金會K/DOQI專家組提出的慢性腎臟病分期建議及糖尿病腎病診斷標(biāo)準(zhǔn),由我院高年資內(nèi)分泌醫(yī)師將50例Ⅱ型糖尿病患者分為三個亞組,分組依據(jù):(1)DKD輕度組(11例):確診的2型糖尿病患者,伴有大量白蛋白尿[隨機晨尿微量白蛋白/肌酐比值(albumin creatinine ratio,ACR)300]和(或)糖尿病視網(wǎng)膜病變伴慢性腎病,估算腎小球率過濾(estimate glomerular filtration rate,eGFR)≥60 ml/min·1.73m~2;(2)DKD中重度組(14例):確診的2型糖尿病患者,伴有大量白蛋白尿(隨機晨尿ACR300)和(或)糖尿病視網(wǎng)膜病變伴慢性腎病,eGFR60 ml/min·1.73m~2;(3)單純糖尿病(simple diabetes,SD)組(25例):確診的2型糖尿病患者,尿蛋白檢查陰性(隨機晨尿ACR30),排除糖尿病視網(wǎng)膜病變及其他慢性腎病。另外招募25性別、年齡相匹配的健康自愿者作為對照。采用德國8通道體部相控陣線圈的Siemens Magnetom Trio 3.0 T超導(dǎo)MRI儀進(jìn)行MRI掃描,行雙腎常規(guī)MRI及ASL MRI掃描,使用Matlab R2013a與Image J軟件對ASL圖像進(jìn)行后處理得到腎皮質(zhì)血流值(cortex of renal blood flow,cRBF)。統(tǒng)計分析采用SPSS18.0軟件,采用組內(nèi)相關(guān)性(Interclass Correlation Coefficient,ICC)對2名醫(yī)師測量的cRBF值進(jìn)行一致性分析,采用單因素方差分析比較各組間cRBF值差異,并采用LSD法進(jìn)行兩兩比較,最后利用Pearson相關(guān)分析cRBF值與eGFR的相關(guān)性。以P0.01有統(tǒng)計學(xué)意義。2、BOLD、DTI MRI評估糖尿病腎臟氧合、水分子彌散水平的研究納入25名單純糖尿病患者(SD)、20名糖尿病腎病患者(DKD)和26名健康志愿者(NC),三組間性別、年齡、BMI相匹配。于磁共振檢查當(dāng)日早晨收集隨機晨尿、靜脈血進(jìn)行生化檢驗,而后根據(jù)MDRD方程計算eGFR值。采用3.0T MR掃描儀行常規(guī)T1、T2排除器質(zhì)性疾病,并采用m GRE序列的BOLD和平面回波(echo-planar imaging,EPI)序列的DTI掃描,獲取的圖像在Siemens工作站進(jìn)行后處理,通過劃取ROI的方式得到單個腎臟皮、髓質(zhì)R2*值、FA、ADC值。采用SPSS18.0軟件對三組受試者年齡、BMI行單因素方差分析,分析性別差異采用c2檢驗;分析左、右腎R2*、MCR、FA、ADC值差異采用配對樣本t檢驗,顯示無差異就取左、右腎平均值進(jìn)行后續(xù)統(tǒng)計分析;采用單因素方差分析比較各組間R2*、MCR、FA、ADC值差異;采用Pearson相關(guān)性分析R2*、MCR、FA、ADC值與eGFR的關(guān)系。結(jié)果:1、DKD的皮質(zhì)灌注水平:配對t檢驗顯示四組組內(nèi)左、右腎cRBF值均無統(tǒng)計學(xué)差異,以其平均值作為個體腎臟cRBF值;對兩名醫(yī)師測量的cRBF值進(jìn)行一致性分析,各組ICC均0.90,說明一致性高。單因素方差分析顯示SD組、DKD輕度組、DKD中重度組、對照組間皮質(zhì)cRBF值存在統(tǒng)計學(xué)差異(F=20.66,P0.01),兩兩比較結(jié)果顯示DKD中重度組cRBF值明顯降低。Pearson相關(guān)性分析顯示糖尿病患者腎皮質(zhì)cRBF值與e GFR呈顯著正相關(guān)(r=0.646,P0.01)。2、DKD的氧合、水分子彌散水平:單因素方差分析顯示三組間MCR、髓質(zhì)FA值存在差異,DKD組MCR值較SD組明顯下降(P=0.001),SD組MCR值較NC組明顯增高(P=0.018),SD組髓質(zhì)FA值顯著高于NC組(P=0.005),DKD組髓質(zhì)FA值顯著低于SD組(P0.01)和NC組(P=0.011);糖尿病患者M(jìn)CR值與eGFR正相關(guān)性(r=0.545,P0.01),糖尿病患者髓質(zhì)FA值與eGFR值也呈正相關(guān)性(r=0.406,P=0.006)。結(jié)論:灌注方面發(fā)現(xiàn)DKD中重度組cRBF值顯著低于其他組,并且cRBF值可反映腎小球濾過率水平,說明DKD會加重腎功能損傷,ASL能夠準(zhǔn)確、簡便、安全的評估糖尿病患者腎皮質(zhì)灌注功能。BOLD和DTI MRI中MCR值和FA值較敏感,早于其他參數(shù)發(fā)現(xiàn)腎臟變化,可以用來評估腎臟功能狀態(tài)和早期發(fā)現(xiàn)腎臟代謝和水分子彌散運動的改變。
[Abstract]:Background and purpose: according to the latest data from the International Diabetes Federation (IDF), the diabetes mellitus (DM) has developed into a global chronic disease. In 2015, the global DM patients reached 415 million, of which the number of Chinese patients reached 109 million. As the kidney is an important target organ for DM, 40% of the patients will send it. Diabetic kidney disease (DKD), DKD is one of the common complications of diabetes and is the primary cause of end-stage renal disease (ESRD). Previous pathophysiological studies have found that renal dysfunction is mainly concentrated on perfusion and oxygenation levels, water molecules in the evolution of diabetes. Three aspects of diffusion movement. Early diabetes is mainly renal cortical perfusion involvement, hyperglycemia acts on the renal tiny blood vessels, activates the renal compensatory mechanism, makes the renal blood supply and renal function enhanced until compensatory disappearance. Meanwhile, the renal oxygenation level also presents a first increase and then decrease, which is basically the same as blood perfusion. When the disease progresses to the skin, the medullary structure and even the fibrosis, the movement of water molecules in the collection system will be restricted, such as no timely treatment, and the final progress is that ESRD. has a strong compensatory capacity for the kidney. We have missed the best time for treatment, so we need to try our best to find early, early diagnosis. At present, the routine routine examination of clinical use is more invasive or needs to use exogenous contrast agent, and it is not able to find abnormal changes in the early stage, and the previous study of DKD is limited to the changes in perfusion or oxygenation, and the lack of renal function. Overall, comprehensive analysis. Only if we fully understand the evolution process of the disease, can we have a new understanding of DKD, early detection and early diagnosis. Therefore, it is urgent to observe the change process of kidney from the angle of perfusion to oxygenation level and water molecular movement, and to observe the change process of kidney in diabetic state. A comprehensive assessment of renal function. With the progress of imaging technology, many new techniques have emerged, such as arterial spin labeling (ASL), blood oxygen level dependence (blood oxygenation level dependent, BOLD), diffusion tensor imaging (diffusion tensor imaging,) and other functional magnetic resonance Nance imaging, fMRI) technology provides us with a reliable, noninvasive technique to solve the predicament encountered above. This study takes these techniques as a grip, according to the law of development and evolution of the disease, contrasts, changes three aspects of renal perfusion, oxygenation level, water molecular diffusion movement, and looks for the imaging evaluation of renal function. The relationship between them is to explore the pathophysiological mechanism of DKD development to provide theoretical support for early detection of DKD. Materials and methods: 1, the study of arterial spin labeling MRI for assessing the level of diabetic renal cortical perfusion was included in 50 patients with type 2 diabetes, according to the staging of chronic kidney disease proposed by the K/ DOQI expert group of the American kidney disease foundation and The diagnostic criteria for diabetic nephropathy were divided into three subgroups of 50 patients with type II diabetes by the senior endocrinologist in our hospital. The group was grouped by: (1) DKD mild group (11 cases): diagnosed type 2 diabetic patients with a large number of albuminuria [random morning urine microalbuminuria / creatinine ratio (albumin creatinine ratio, ACR) 300] and / or diabetic retina The disease was associated with chronic kidney disease (estimate glomerular filtration rate, eGFR) more than 60 ml/min. 1.73m~2; (2) severe DKD group (14 cases): diagnosed type 2 diabetic patients with a large number of albuminuria (random morning urine ACR300) and (or) diabetic retinopathy with chronic kidney disease, eGFR60 ml/min. (3) simple diabetes (3) Simple diabetes, SD) group (25 cases): diagnosed type 2 diabetic patients with negative urinary protein examination (random morning urine ACR30), excluding diabetic retinopathy and other chronic kidney disease. Also recruited 25 sex, age matched healthy volunteers as control. Using the Siemens Magnetom Trio 3 T of the German 8 passages phased array coil, superconducting MRI The MRI scan was performed with a double kidney routine MRI and ASL MRI scan. The renal cortical blood flow values were obtained by the Matlab R2013a and Image J software after the post-processing of the ASL images. The cRBF value difference between each group was compared by single factor analysis of variance, and the LSD method was used to compare the cRBF values. Finally, the correlation between cRBF and eGFR was used to analyze the cRBF value of Pearson, BOLD, DTI MRI evaluation of diabetic renal oxygenation, and the study of the water molecular diffusion level was included in the 25 list of pure diabetic patients. People (SD), 20 diabetic nephropathy patients (DKD) and 26 healthy volunteers (NC), three groups of sex, age, and BMI were matched. In the morning of the magnetic resonance examination, random morning urine was collected, venous blood was tested by biochemical test, and then the eGFR value was calculated according to the MDRD equation. The 3.0T MR scanner was used for routine T1, T2 ruled out organic diseases, and m GRE sequence was used. DTI scanning of LD and echo-planar imaging (EPI) sequences, the acquired images were processed after Siemens workstation, single kidney skin, R2* value of medulla, FA, ADC values were obtained by using ROI method. SPSS18.0 software was used for three groups of subjects' age, BMI row mono ANOVA analysis, analysis of gender differences, and analysis left, right The R2*, MCR, FA, and ADC values of the kidney were compared with the paired sample t test. The mean values of left and right kidney were statistically analyzed without difference, and the difference of R2*, MCR, FA, ADC values were compared by single factor analysis of variance, and the relationship between R2*, MCR, and the value of R2* was analyzed by Pearson correlation. Results: 1 There was no statistical difference between the left and right renal cRBF values in the four groups. The average value of the kidney was used as the cRBF value of the individual kidney. The cRBF values measured by two doctors were analyzed, and the ICC was 0.90 in each group. The single factor variance analysis showed that the SD group, the DKD mild group, the DKD medium severe group and the control group were statistically different (F=20.66, P). 0.01), the results of 22 comparison showed that the cRBF value of DKD in the moderate and severe group decreased significantly by the.Pearson correlation analysis. The renal cortical cRBF value was significantly positively correlated with e GFR (r=0.646, P0.01).2, DKD oxygenation and water molecular diffusion level: the single factor variance analysis showed that the three groups were MCR, and the medulla FA values were significantly different. (P=0.001), the value of MCR in group SD was significantly higher than that in group NC (P=0.018), and the FA value of medulla in group SD was significantly higher than that in NC group (P=0.005), and the FA value of medulla in the DKD group was significantly lower than that of the SD group. The cRBF value of DKD medium and severe group was significantly lower than that of other groups, and the cRBF value could reflect the glomerular filtration rate, indicating that DKD would aggravate renal function damage. ASL can be accurate, simple and safe to evaluate the MCR value and FA value of renal cortical perfusion function in diabetic patients,.BOLD and DTI MRI more sensitive than other parameters, which can be used to detect renal changes. Evaluation of renal function and early detection of renal metabolism and diffusion of water molecules.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R445.2;R587.2;R692.9

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