老年肾活检患者疾病谱及老年特发性膜性肾病临床特征研究

发布时间：2018-08-22 07:34

【摘要】：背景和目的：我国人口老龄化趋势严重,老年人群发生肾脏病的比例很高,明确老年肾病疾病谱具有重要意义。肾活检作出的病理诊断最有价值,但老年肾病患者多不接受肾活检,缺乏病理诊断疾病谱,而国外研究又无法代表我国情况,国内大规模研究并不多。尽管老年病理诊断疾病谱的具体特点尚有待研究,但明确的是特发性膜性肾病(Idiopathic Membranous Nephropathy, IMN)最常见,应重点关注；明确老年IMN相对于非老年IMN以及其它老年病理类型的临床特征具有积极意义。基于以上原因,本研究回顾性分析老年肾活检患者及IMN患者的病历资料,目的在于明确老年肾病病理诊断疾病谱以及老年IMN患者的临床特征。对象和方法：第一部分研究对象是2004年至2013年我院肾脏病科老年肾活检患者,临床诊断包括肾病综合征(Nephrotic Syndrome, NS)、慢性肾炎综合征、急进性肾炎、小管间质疾病；肾功能分类为慢性肾衰竭(Chronic Renal Failure,CRF)、急性肾损伤(Acute Kidney Injury, AKI)、肾功能基本正常。主要分析了临床诊断、病理诊断疾病谱,,临床诊断与病理诊断、肾功能的对应关系,特别分析了AKI对应的病理诊断。第二部分研究对象是我院肾脏病科2004年至2013年的IMN患者,按照年龄分为老年、非老年两组,记录患者的临床特征,包括年龄、性别、体重指数(Body Mass Index, BMI)、血压水平以及主要实验室检验,同时记录患者病理指标,包括肾小球、肾小管／间质、肾小动脉病变。主要分析了老年、非老年临床特征和病理指标的差异,每组的临床、病理联系。第三部分研究对象是表现为NS的老年IMN和老年微小病变型肾病患者,记录临床特征及实验室检验结果,比较两种疾病的差异,并尝试建立鉴别方程。统计分析采用t检验、ANOVA、 Kruskal-Wallis H去、χ2检验、Logistic回归、ROC作图法,所有数据使用SPSS 20.0统计软件处理。结果：老年肾活检患者总计796例,男女比为1.4：1,平均年龄66.9±5.4岁,肾活检患者数量逐渐增加,但是占同期住院老年肾病患者比例并未表现出同样趋势。临床诊断主要是NS(458例,57.53%)和慢性肾炎综合征(287例,36.05%),且NS占比逐渐升高,慢性肾炎综合征占比逐渐下降。原发性肾小球疾病是老年肾活检患者最主要病理类型,共587例,占73.7%,继发性肾小球疾病173例,占21.73%,IMN是原发性肾小球疾病的首位病因,占44.63%,糖尿病肾病是继发性肾小球疾病的首位病因,占24.28%；全部肾活检患者中前三位病因分别是IMN(262例,32.91%),IgA肾病(130例,16.33%),微小病变型肾病(Minimal Change Disease,MCD)68例,占8.54%,其中IMN占比逐渐升高。NS首位病因是IMN,慢性肾炎综合征首位病因是IgA肾病,急进性肾炎综合征首位病因是ANCA相关性小血管炎肾损害。AKI的首位病因是MCD,第二位病因是ANCA相关性小血管炎肾损害。IMN患者1058例,年龄47.38±14.43岁,男女比为1.3：1,老年组占21.17%,非老年组占78.8%。老年组IMN检出率显著高于非老年组。近10年老年、非老年IMN占肾活检比例逐渐增加,但是各组构成比相对稳定。临床特征中BMI、血红蛋白、肾小球滤过率、血肌酐、血磷、IgG、IgA、纤维蛋白原、尿渗透压、血压水平、高血压发生率、2型糖尿病发生率、血尿发生率在两组间有显著性差异,且和增龄的自然趋势一致。重要的临床评价指标血清白蛋白和24h尿蛋白在两组间无显著差异,总胆固醇、甘油三酯、低密度脂蛋白在NS人群中老年组显著低于非老年组,两组降脂药物应用无显著差异。病理指标中肾小球全球硬化评分、发生率,肾小管间质病变评分、发生率,肾小动脉病变发生率在两组间有显著性差异,且和增龄的自然趋势一致。肾小球全球硬化的独立相关因素在老年组是合并高血压,非老年组是年龄、合并2型糖尿病、平均动脉压、血尿酸。临床表现为NS的老年IMN患者162例,年龄67.4±5.2岁,老年MCD患者58例,年龄66.9±5.9岁,结果显示IMN组的血尿发生率、24h尿蛋白定量、eGFR显著高于MCD,AKI发生率、血肌酐、C3、C4、纤维蛋白原显著低于MCD组,其它临床指标均无显著性差异。按照单因素筛选、二元logistic回归法、ROC作图法相结合的统计方法建立两个IMN和MCD的鉴别方程。方程一将C3、C4、Fib按连续变量进行处理,结果显示血尿(OR=0.24,95% C.I：0.11～0.56)、AKI(OR=21.44,95% C.I：6.65～69.12)、纤维蛋白原(OR=1.52,95% C.I：1.16～1.99)是具有鉴别意义的临床指标,方程一的预测概率的ROC曲线下面积是0.831。方程二将C3、C4、纤维蛋白原根据ROC作图法找出最佳判断界值,转化为2分类变量后,结果显示血尿(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).纤维蛋白原是否5.5g/L(OR=2.66,95% C.I：1.14～6.19)是具有鉴别意义的临床指标,方程二的预测概率的ROC曲线下面积是0.843。结论：原发性肾小球疾病仍是老年肾活检患者最主要的病理类型；IMN是老年肾活检患者首位病因,也是引起NS的首位病因,其所占趋势逐渐增加,引起慢性肾炎综合征的首位病因是IgA肾病,引起AKI的首位病因是MCD。应重视老年IMN的诊断和治疗,老年MCD患者AKI的防治。肾活检患者IMN检出率总体呈增加趋势,并非老年组特征。老年IMN患者临床指标和病理指标的差异受增龄的影响,与增龄的自然趋势一致；但合并NS老年IMN患者血脂水平未呈现与增龄一致的变化,应重视这部分患者肝脏功能的保护。IMN非老年患者要注意防治2型糖尿病、降低血压、血尿酸水平,老年患者尤其要注意防治高血压,以防止肾小球全球硬化加重。表现为NS的老年IMN与老年MCD相比,血尿和AKI发生率明显升高,而血清补体水平低下。初步提出老年IMN和MCD的鉴别方程,可为老年NS患者的诊断提供借鉴。
[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.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R692
，

本文编号：2196418