血清抗PLA2R抗体在评价特发性膜性肾病预后作用中的单中心队列研究

发布时间：2018-04-29 01:38

本文选题：特发性膜性肾病 + 抗PLA2R抗体　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:通过单中心队列研究探讨血清抗磷脂酶A2受体(phospholipase A2-receptor,PLA2R)抗体在评价特发性膜性肾病(Idiopathic Membranous Nephropathy,IMN)患者预后中的作用。方法:1.选取2011年3月至2016年2月首次在北京大学深圳医院肾内科住院行肾穿刺活检,病理诊断为IMN患者259例,其中男性142例,女性117例,平均年龄为41.75±14.45岁,并对这些患者进行随访,随访时间截止至2016年7月(其中随访血清收集时间为2015年7月至2016年7月)。2.收集患者基线及随访资料,包括一般资料如性别,发病年龄、活检时年龄等,及临床生化指标如尿常规、随机尿蛋白/肌酐比值、24小时尿蛋白定量、血白蛋白(serum albumin,ALB)、血肌酐(serum creatinine,Scr)、估计肾小球滤过率(estimate glomerular filtration rate,e GFR)、尿素氮(blood urea nitrogen,BUN)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、随访过程中治疗情况。3.利用间接酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测259例IMN患者肾穿当天及部分患者随访过程中血清抗PLA2R抗体滴度,其中20RU/ml为阴性,20RU/ml为阳性结果,根据血清抗PLA2R抗体滴度分为阳性组和阴性组。4.应用SPSS 19.0及Stata 14.0软件进行统计学分析,P0.05代表差异有统计学意义。结果:1.259例IMN患者中抗PLA2R抗体阳性患者133例,阳性率为51.35%。抗体阳性组较阴性组患者血ALB低,尿蛋白高、年龄较大(P0.05),而两组患者间性别、Scr、e GFR并无统计学意义(P0.05)。简单线性相关分析发现抗体滴度与蛋白尿呈正相关,与血ALB呈负相关(P0.001)。2.166例完成随访,随访中位时间24个月,其中男性95例,女性71例,血清抗体阳性率为53.01%。随访过程中所有患者都使用支持治疗,仅有62例患者使用免疫抑制剂。两组间年龄、性别、Scr、e GFR、随访时间、是否接受免疫抑制剂治疗无统计学差异(P0.05),阳性组较阴性组的血ALB较低、尿蛋白量高(P0.05)。3.166例IMN患者随访中位时间24个月后,68例获得完全缓解,73例自发缓解,进入终末期肾脏病的患者0例。统计分析结果提示阴性组的完全缓解率及自发缓解率高于阳性组(52.56 VS 30.68%,P=0.001及56.72 VS 44.87%,P=0.02),Kaplan-Meier曲线也提示阴性组患者达到完全缓解早于阳性组。通过COX回归分析,调整了年龄、性别、ALB、Scr、尿蛋白等混杂因素后,发现基线抗体滴度升高是影响IMN疾病完全缓解的风险因子,抗体滴度每升高10RU/ml,IMN未达到完全缓解风险增加54%。比较疾病活动不同的三组,发现疾病活动组抗体滴度平均数明显高于完全缓解和部分缓解组,疾病活动组患者较完全缓解组年龄较大、男性所占比例较高、随访中接受免疫抑制剂治疗的患者比例高。4.对27例患者随访12月,观察到抗PLA2R抗体滴度下降或转阴早于蛋白尿。结论:1.我中心IMN患者中血清抗PLA2R抗体阳性率为51.35%。抗体阳性组患者较阴性组血白蛋白低、尿蛋白高。2.随访中位时间24个月,我中心IMN患者完全缓解率52.56%,自发缓解率50.34%,其中进入终末期肾脏病患者0例。抗PLA2R抗体阴性组完全缓解率及自发缓解率高于阳性组。COX回归分析提示基线抗体滴度升高是IMN疾病不能完全缓解的风险因子,抗体滴度每升高10RU/ml,IMN患者未达到完全缓解的风险增加54%。3.抗PLA2R抗体滴度下降或转阴早于蛋白尿,监测血清抗PLA2R抗体滴度是监测疾病活动及治疗效果更敏感的指标。
[Abstract]:Objective: To investigate the role of serum anti phospholipase A2 receptor (phospholipase A2-receptor, PLA2R) antibody in the evaluation of the prognosis of patients with idiopathic membranous nephropathy (Idiopathic Membranous Nephropathy, IMN) by single center cohort study. Methods: 1. to choose the first renal biopsy in the Department of Nephrology of Shenzhen hospital, Peking University, from March 2011 to February 2016. Biopsy and pathological diagnosis were performed in 259 IMN patients, including 142 males and 117 females with an average age of 41.75 + 14.45 years of age. The follow-up period was followed up to July 2016 (in which the follow-up period was from July 2015 to July 2016).2. collected the patients' baseline and follow-up data, including general data such as sex, and the onset of the disease. Age, age of biopsy, and clinical biochemical parameters such as urine routine, random urine protein / creatinine ratio, 24 hour urine protein quantitative, serum albumin, ALB, serum creatinine, Scr, estimated glomerular filtration rate (estimate glomerular filtration rate, e GFR), urea nitrogen, triglyceride IDE, TG), total cholesterol (total cholesterol, TC), and in the follow-up process,.3. was detected by indirect enzyme linked immunosorbent assay (enzyme linked immunosorbent assay, ELISA) in 259 cases of kidney penetration and some patients. LA2R antibody titer was divided into positive group and negative group.4. application SPSS 19 and Stata 14 software for statistical analysis. The difference of P0.05 representative was statistically significant. Results: 1.259 cases of IMN patients with positive anti PLA2R antibody were 133 cases, the positive rate was lower in 51.35%. antibody positive group than in negative group, and the urine protein was high, and the age was larger (P0.05), but two The gender, Scr, and E GFR were not statistically significant (P0.05). Simple linear correlation analysis found that the antibody titer was positively correlated with proteinuria and was negatively correlated with blood ALB (P0.001).2.166 cases completed for 24 months, including 95 males and 71 females, and the positive rate of serum antibody was used in all patients during the follow-up of 53.01%.. Support therapy, only 62 patients were treated with immunosuppressive agents. Two groups of age, sex, Scr, e GFR, follow-up time, no statistical difference in the treatment of immunosuppressive agents (P0.05), the positive group was lower than the negative group, the urine protein was high (P0.05).3.166 case IMN patients were followed up at the median time of 24 months, 68 cases had complete remission, 73 cases spontaneous. The results of 0 patients with end-stage renal disease showed that the rate of complete remission and spontaneous remission in the negative group was higher than that of the positive group (52.56 VS 30.68%, P=0.001 and 56.72 VS 44.87%, P=0.02), and the Kaplan-Meier curve suggested that the negative group had complete remission earlier than the positive group. The age, sex and sex were adjusted by the COX regression analysis. ALB, Scr, urinary protein and other confounding factors, it was found that the increase in the titer of the baseline antibody was a risk factor for the complete remission of the IMN disease. The antibody titer increased by 10RU/ml, and the IMN did not reach the total remission risk, which increased the 54%. comparison of the disease activity in three groups, and found that the average number of antibody titers in the disease group was significantly higher than that of the complete remission and the partial delay. The patients in the group of disease active group were older than the complete remission group, and the proportion of men was higher. The proportion of patients receiving immunosuppressive therapy in the follow-up was high.4. to 27 patients followed up in December. The anti PLA2R antibody titer decreased or turned negative to proteinuria. Conclusion: 1. the positive rate of serum anti PLA2R antibody in IMN patients in the center of my center is 51.35%. anti 51.35%.. In the positive group, the blood albumin was low in the negative group and the high.2. follow-up time was 24 months. The complete remission rate was 52.56%, the spontaneous remission rate was 50.34%, of which 0 were in the end-stage renal disease. The complete remission rate and spontaneous remission rate of the anti PLA2R negative group were higher than the positive group.COX regression analysis suggested the baseline antibody drop. The increase of degree is a risk factor for IMN disease, and the antibody titer increases by 10RU/ml. The risk of IMN patients not reaching complete remission increases the drop of 54%.3. anti PLA2R antibody titer or turns negative to proteinuria. The monitoring of serum anti PLA2R antibody titer is a more sensitive indicator for monitoring disease activity and treatment effect.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692

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