【摘要】：背景和目的：我國人口老齡化趨勢嚴(yán)重,老年人群發(fā)生腎臟病的比例很高,明確老年腎病疾病譜具有重要意義。腎活檢作出的病理診斷最有價值,但老年腎病患者多不接受腎活檢,缺乏病理診斷疾病譜,而國外研究又無法代表我國情況,國內(nèi)大規(guī)模研究并不多。盡管老年病理診斷疾病譜的具體特點尚有待研究,但明確的是特發(fā)性膜性腎病(Idiopathic Membranous Nephropathy, IMN)最常見,應(yīng)重點關(guān)注；明確老年IMN相對于非老年IMN以及其它老年病理類型的臨床特征具有積極意義。基于以上原因,本研究回顧性分析老年腎活檢患者及IMN患者的病歷資料,目的在于明確老年腎病病理診斷疾病譜以及老年IMN患者的臨床特征。對象和方法：第一部分研究對象是2004年至2013年我院腎臟病科老年腎活檢患者,臨床診斷包括腎病綜合征(Nephrotic Syndrome, NS)、慢性腎炎綜合征、急進性腎炎、小管間質(zhì)疾病；腎功能分類為慢性腎衰竭(Chronic Renal Failure,CRF)、急性腎損傷(Acute Kidney Injury, AKI)、腎功能基本正常。主要分析了臨床診斷、病理診斷疾病譜,,臨床診斷與病理診斷、腎功能的對應(yīng)關(guān)系,特別分析了AKI對應(yīng)的病理診斷。第二部分研究對象是我院腎臟病科2004年至2013年的IMN患者,按照年齡分為老年、非老年兩組,記錄患者的臨床特征,包括年齡、性別、體重指數(shù)(Body Mass Index, BMI)、血壓水平以及主要實驗室檢驗,同時記錄患者病理指標(biāo),包括腎小球、腎小管／間質(zhì)、腎小動脈病變。主要分析了老年、非老年臨床特征和病理指標(biāo)的差異,每組的臨床、病理聯(lián)系。第三部分研究對象是表現(xiàn)為NS的老年IMN和老年微小病變型腎病患者,記錄臨床特征及實驗室檢驗結(jié)果,比較兩種疾病的差異,并嘗試建立鑒別方程。統(tǒng)計分析采用t檢驗、ANOVA、 Kruskal-Wallis H去、χ2檢驗、Logistic回歸、ROC作圖法,所有數(shù)據(jù)使用SPSS 20.0統(tǒng)計軟件處理。結(jié)果：老年腎活檢患者總計796例,男女比為1.4：1,平均年齡66.9±5.4歲,腎活檢患者數(shù)量逐漸增加,但是占同期住院老年腎病患者比例并未表現(xiàn)出同樣趨勢。臨床診斷主要是NS(458例,57.53%)和慢性腎炎綜合征(287例,36.05%),且NS占比逐漸升高,慢性腎炎綜合征占比逐漸下降。原發(fā)性腎小球疾病是老年腎活檢患者最主要病理類型,共587例,占73.7%,繼發(fā)性腎小球疾病173例,占21.73%,IMN是原發(fā)性腎小球疾病的首位病因,占44.63%,糖尿病腎病是繼發(fā)性腎小球疾病的首位病因,占24.28%；全部腎活檢患者中前三位病因分別是IMN(262例,32.91%),IgA腎病(130例,16.33%),微小病變型腎病(Minimal Change Disease,MCD)68例,占8.54%,其中IMN占比逐漸升高。NS首位病因是IMN,慢性腎炎綜合征首位病因是IgA腎病,急進性腎炎綜合征首位病因是ANCA相關(guān)性小血管炎腎損害。AKI的首位病因是MCD,第二位病因是ANCA相關(guān)性小血管炎腎損害。IMN患者1058例,年齡47.38±14.43歲,男女比為1.3：1,老年組占21.17%,非老年組占78.8%。老年組IMN檢出率顯著高于非老年組。近10年老年、非老年IMN占腎活檢比例逐漸增加,但是各組構(gòu)成比相對穩(wěn)定。臨床特征中BMI、血紅蛋白、腎小球濾過率、血肌酐、血磷、IgG、IgA、纖維蛋白原、尿滲透壓、血壓水平、高血壓發(fā)生率、2型糖尿病發(fā)生率、血尿發(fā)生率在兩組間有顯著性差異,且和增齡的自然趨勢一致。重要的臨床評價指標(biāo)血清白蛋白和24h尿蛋白在兩組間無顯著差異,總膽固醇、甘油三酯、低密度脂蛋白在NS人群中老年組顯著低于非老年組,兩組降脂藥物應(yīng)用無顯著差異。病理指標(biāo)中腎小球全球硬化評分、發(fā)生率,腎小管間質(zhì)病變評分、發(fā)生率,腎小動脈病變發(fā)生率在兩組間有顯著性差異,且和增齡的自然趨勢一致。腎小球全球硬化的獨立相關(guān)因素在老年組是合并高血壓,非老年組是年齡、合并2型糖尿病、平均動脈壓、血尿酸。臨床表現(xiàn)為NS的老年IMN患者162例,年齡67.4±5.2歲,老年MCD患者58例,年齡66.9±5.9歲,結(jié)果顯示IMN組的血尿發(fā)生率、24h尿蛋白定量、eGFR顯著高于MCD,AKI發(fā)生率、血肌酐、C3、C4、纖維蛋白原顯著低于MCD組,其它臨床指標(biāo)均無顯著性差異。按照單因素篩選、二元logistic回歸法、ROC作圖法相結(jié)合的統(tǒng)計方法建立兩個IMN和MCD的鑒別方程。方程一將C3、C4、Fib按連續(xù)變量進行處理,結(jié)果顯示血尿(OR=0.24,95% C.I：0.11～0.56)、AKI(OR=21.44,95% C.I：6.65～69.12)、纖維蛋白原(OR=1.52,95% C.I：1.16～1.99)是具有鑒別意義的臨床指標(biāo),方程一的預(yù)測概率的ROC曲線下面積是0.831。方程二將C3、C4、纖維蛋白原根據(jù)ROC作圖法找出最佳判斷界值,轉(zhuǎn)化為2分類變量后,結(jié)果顯示血尿(OR=0.28,95%C.I：0.12～0.66)、AKI(OR=27.39.95%C.I:8.01～93.6)、C3是否≥115md/dl(OR=3.53.95% C.I:1.43～8.76).纖維蛋白原是否5.5g/L(OR=2.66,95% C.I：1.14～6.19)是具有鑒別意義的臨床指標(biāo),方程二的預(yù)測概率的ROC曲線下面積是0.843。結(jié)論：原發(fā)性腎小球疾病仍是老年腎活檢患者最主要的病理類型；IMN是老年腎活檢患者首位病因,也是引起NS的首位病因,其所占趨勢逐漸增加,引起慢性腎炎綜合征的首位病因是IgA腎病,引起AKI的首位病因是MCD。應(yīng)重視老年IMN的診斷和治療,老年MCD患者AKI的防治。腎活檢患者IMN檢出率總體呈增加趨勢,并非老年組特征。老年IMN患者臨床指標(biāo)和病理指標(biāo)的差異受增齡的影響,與增齡的自然趨勢一致；但合并NS老年IMN患者血脂水平未呈現(xiàn)與增齡一致的變化,應(yīng)重視這部分患者肝臟功能的保護。IMN非老年患者要注意防治2型糖尿病、降低血壓、血尿酸水平,老年患者尤其要注意防治高血壓,以防止腎小球全球硬化加重。表現(xiàn)為NS的老年IMN與老年MCD相比,血尿和AKI發(fā)生率明顯升高,而血清補體水平低下。初步提出老年IMN和MCD的鑒別方程,可為老年NS患者的診斷提供借鑒。
[Abstract]:BACKGROUND AND OBJECTIVE: There is a serious trend of aging population in China, and the incidence of kidney disease in the elderly is very high. It is of great significance to clarify the spectrum of geriatric nephropathy. Although the specific characteristics of the disease spectrum of pathological diagnosis in the elderly remain to be studied, it is clear that idiopathic membranous nephropathy (IMN) is the most common and should be paid more attention to. Based on the above reasons, this study retrospectively analyzed the medical records of elderly renal biopsy patients and IMN patients in order to clarify the spectrum of pathological diagnosis of elderly renal disease and the clinical characteristics of elderly IMN patients. Nephrotic Syndrome (NS), Chronic Nephritis Syndrome, Acute Progressive Nephritis, Tubulointerstitial Diseases, Chronic Renal Failure (CRF), Acute Kidney Injury (AKI), Kidney Function is basically normal. The second part is the study of IMN patients in the nephrology department of our hospital from 2004 to 2013. The patients were divided into two groups according to their age. The clinical characteristics of the patients were recorded, including age, sex, body mass index (BMI), blood pressure level and main facts. Laboratory tests were performed and pathological parameters including glomerulus, tubulointerstitium and small renal artery lesions were recorded.The differences of clinical and pathological features between the elderly and non-elderly were analyzed.The clinical and pathological relationships of each group were analyzed. Statistical analysis was performed by t-test, ANOVA, Kruskal-Wallis H, _2 test, logistic regression and ROC plotting. All data were processed by SPSS 20.0 statistical software. Results: 796 elderly renal biopsy patients with a male-female ratio of 1.4:1, mean age 66. The number of renal biopsy patients increased gradually at the age of 9 The main pathological types were 587 cases (73.7%) and 173 cases (21.73%) of secondary glomerular diseases. IMN was the first cause of primary glomerular diseases (44.63%). Diabetic nephropathy was the first cause of secondary glomerular diseases (24.28%). The top three causes of all renal biopsy patients were IMN (262 cases, 32.91%) and IgA nephropathy (130.63%). The first cause of NS was IMN, the first cause of chronic nephritis syndrome was IgA nephropathy, and the first cause of rapid progressive nephritis syndrome was ANCA-related vasculitis and nephropathy. The first cause of AKI was MCD and the second was ANCA-related vasculitis and nephropathy. The detection rate of IMN in the elderly group was significantly higher than that in the non-elderly group. In the past 10 years, the proportion of non-elderly IMN in renal biopsy gradually increased, but the composition of each group was relatively stable. Glomerular filtration rate, serum creatinine, serum phosphorus, IgG, IgA, fibrinogen, urinary osmotic pressure, blood pressure level, hypertension, incidence of type 2 diabetes mellitus, and incidence of hematuria were significantly different between the two groups, and were consistent with the natural trend of aging. Glycerol, triglyceride and low density lipoprotein were significantly lower in the elderly group than in the non-elderly group. There was no significant difference in the use of lipid-lowering drugs between the two groups. The independent correlative factors of glomerular sclerosis were hypertension in the elderly group, age in the non-elderly group, type 2 diabetes mellitus, mean arterial pressure, and serum uric acid. The clinical manifestations of 162 elderly IMN patients with NS, aged 67.4 (+ 5.2), 58 elderly MCD patients, aged 66.9 (+ 5.9). The results showed that the incidence of hematuria in the IMN group, 24 h urinary protein. Quantitatively, eGFR was significantly higher than MCD, AKI incidence, serum creatinine, C3, C4, fibrinogen were significantly lower than MCD group, other clinical indicators were not significantly different. The results showed that hematuria (OR = 0.24, 95% C.I: 0.11-0.56), AKI (OR = 21.44, 95% C.I: 6.65-69.12), fibrinogen (OR = 1.52, 95% C.I: 1.16-1.99) were the clinical indicators with differential significance. The area under ROC curve of the prediction probability of equation 1 was 0.831. Equation 2 identified the best boundaries of C3, C4 and fibrinogen according to ROC plotting method. The results showed that hematuria (OR = 0.28, 95% C.I: 0.12-0.66), AKI (OR = 27.39.95% C.I: 8.01-93.6), C3 (OR = 3.53.95% C.I: 1.43-8.76). Fibrinogen 5.5 g/L (OR = 2.66, 95% C.I: 1.14-6.19) was a clinical marker of differential significance. Conclusion: Primary glomerular disease is still the most important pathological type in elderly patients with renal biopsy; IMN is the first cause of renal biopsy in elderly patients, but also the first cause of NS, the trend is gradually increasing, the first cause of chronic nephritis syndrome is IgA nephropathy, the first cause of AKI is MCD. Diagnosis and treatment, prevention and treatment of AKI in elderly patients with MCD. The overall detection rate of IMN in renal biopsy patients showed an increasing trend, not the characteristics of the elderly group. Non-elderly patients with IMN should pay attention to the prevention and treatment of type 2 diabetes mellitus, lowering blood pressure and serum uric acid level. Elderly patients should pay special attention to the prevention and treatment of hypertension to prevent the aggravation of glomerular sclerosis. The differential equation of IMN and MCD in elderly patients is preliminarily proposed. It can provide reference for the diagnosis of NS in elderly patients.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R692
，

本文編號：2196418