【作者】 刘霞；

【导师】 胡伟新；

【作者基本信息】 南京大学 ， 内科学， 2016， 硕士

【摘要】 背景:ANCA相关性肾炎的形态学以肾小球节段性袢坏死伴新月体形成、肾小球无或仅少量免疫球蛋白沉积为特征。目前国际上将AAGN肾脏病变分为四型:局灶型、新月体型、混合型和硬化型。如果50%以上肾小球有新月体形成则称之为新月体型AAGN。新月体型AAGN发病迅速,临床通常表现为急进性肾功能减退,需要强化免疫抑制治疗甚至是血浆置换治疗。但由于新月体大小和比例不一、正常肾小球及肾小球硬化比例不一、肾小管间质受损程度不同,造成临床表现和病理特征差异性很大。AAGN对治疗的反应以及预后差别较大,部分患者虽经积极强化免疫抑制治疗(包括甲泼尼龙冲击、静脉用环磷酰胺、血浆置换等),肾功能难以恢复而需维持性透析治疗。同时,强化免疫抑制治疗会带来严重感染,这也是AAGN患者死亡的主要原因。因此,临床上需要充分评估治疗选择,并且在决定治疗方案前评估疗效-风险比是非常重要的。但如何预测治疗反应、有哪些因素影响远期预后,目前仍缺乏研究。目的:探讨影响新月体型抗中性粒细胞胞质抗体(ANCA)相关性肾炎(AAGN)的治疗反应及远期预后的因素。方法:60例经肾活检诊断为新月体型AAGN患者(男25例,女35例),中位年龄54岁,基线平均SCr 5.0±2.9mg/dl。根据入院是否需要肾脏替代治疗(RRT)分为RRT组(n=30)和非RRT组(n=30)。以治疗3个月时RRT组摆脱RRT、非RRT组SCr下降≥25%定义为治疗反应良好(GR),否则为治疗无反应(NR)。肾脏组织学损伤指标包括正常肾小球比例、总新月体比例、环状体比例、环状体/总新月体、球性硬化等。肾小管间质病变采用半定量评分,分为轻度(1分)、中度(2分)、重度(3分)。多因素Cox回归分析新月体型AAGN临床及病理指标与治疗反应及远期肾存活的相关性。结果:RRT组年龄、BVAS评分和SCr水平显著高于非RRT组,RRT组环状新月体占新月体的比例高于非RRT组(但无统计学差别),其它病理指标(总细胞性新月体、肾小球硬化比例)两组间均无差异。诱导治疗3个月时共有4例死亡(RRT组3例,非RRT组1例),40例治疗反应良好(RRT组16例,非RRT组24例),16例治疗无反应(RRT组11例,非RRT组5例)。多因素Cox回归分析发现环状体占新月体的比例是影响RRT组能否摆脱RRT的主要因素(HR=17.24(CI 1.16～255.63),p=0.038),环状体占新月体的比例≥50%时不能摆脱RRT的风险显著增大(HR=22.2(CI 2.17～255.63),p=0.002);而在非RRT组,GR患者正常肾小球比例显著高于NR,正常肾小球比例>7%时治疗反应好的可能性显著增大(HR=13.3(CI 1.7～107.4),p=0.006)。中位随访时间19个月(6～58月),6例(10%)死亡,18例(30%)进入终末期肾病。5年人存活率为87.4%,肾存活率仅为56.0%。多因素Cox回归分析发现需RRT及肾病范围内蛋白尿为影响远期肾脏存活率的独立危险因素。结论:环状体占总新月体的比例及正常肾小球比例分别是影响需RRT和不需RRT的新月体型AAGN患者治疗反应的主要因素;需RRT及大量蛋白尿是影响肾脏远期预后的主要因素。研究表明肾脏病理指标对于制定新月体型AAGN合理治疗方案及判断预后是必需的。更多还原

【Abstract】 Background:The morphological features of Anti-neutrophil cytoplasmic antibodies associated glomerulonephritis(AAGN)are segmental necrosis with crescents and "pauci-immune" deposition in glomeruli.The AAGN are now divided into four histological classes:Focal,crescentic,mixed,and sclerotic.In crescentic AAGN,more than 50%glomeruli show cellular crescents.The patients with AAGN usually present rapidly progressive renal failure and require intensive immunosuppressive treatment and even plasma exchange.But the clinical manifestations and histological features are heterogeneity because of different ratio of crescents,normal glomeruli,glomerulosclerosis and tubulointerstitial lesion.The treatment response and renal survival are much different,renal function will not recover even after the intensive immunosuppressive therapies,such as MP pulse therapy,Ⅳ-CTX,plasma exchange.Meanwhile,intensive immunosuppressive therapies have high incidence of infection,which is the leading cause of death in AAGN patients.Therefore,treatment choices should be fully evaluated,and it is very important to evaluate the benefit and risks prior to make treatment decision.However,few researches have been made in patients with crescentic AAGN to predict the treatment response and long-term renal survival.Objective:In this study,we analyze the factors which may predict treatment response and long-term renal outcome in Chinese patients with crescents AAGN.Methodology:60 cases with renal biopsy proven crescentic AAGN were included in the study(male 25,female 30,median age 54 years(IQR),mean SCr 5.0±2.9mg/dl).According to whether the renal replacement therapy(RRT)was needed on admission,the patients were divided two groups,the RRT group(n=30)and non-RRT group(n=30).The treatment response was defined as good response(GR)and non-response(NR),according to the renal function after 3 months induction treatment.The GR was defined as the patients get rid of RRT in RRT group and the SCr decreased by 25%in non-RRT group or more,otherwise,the treatment was defined as NR.Histological lesions included the ratio of normal glomeruli,total cellular crescents,circumferential crescents,circumferential/total crescents,sclerotic glomeruli.Tubulointerstitial lesions were scored semiquantitatively as mild(1’),moderate(2’)and severe(3’).Multivariate Cox regression analysis was applied to evaluate clinical and histologic features predicting treatment response and long-term renal outcome in crescentic AAGN.Results:Age,BVAS score and SCr level were much higher in RRT Group than that in non-RRT Group.The percentage of circumferential crescents/total crescents in RRT Group was higher than that in non-RRT Group,but without statistical differences.Total cellular crescents and the ratio of sclerotic glomeruli showed no differences between the two groups.At three months induction treatment,four patients died(3 in RRT group,1 in non-RRT group),40 patients showed GR(16 in RRT group,24 in non-RRT group),16 patients were NR(11 in RRT group,5 in non-RRT group).According to multivariate Cox regression analysis,the percentage of circumferential crescents/total crescents was the main factor affecting the treatment response in RRT group(HR=17.24(CI 1.16～255.63),p=0.038),with the percentage≥50%being the high risk to be NR(HR=22.2(CI 2.17～200),p=0.002).In the non-RRT Group,the ratio of normal glomeruli in GR patients was significantly higher than that in NR patients.When the ratio of normal glomeruli was higher than 7%,the treatment response was more likely to be GR(HR=13.3(CI 1.7～107.4),p=0.006).During a median follow-up of 19 months(6～58 months),6 patients(10%)dead and 18(30%)patients developed to ESRD.The 5 year patient and renal survival were 87.4%and 56.0%,respectively.Multivariate Cox analysis showed that the need of RRT and nephrotic range of proteinuria were the independent risk factors for long-term renal survival.Conclusion:For patients with crescentic AAGN,the extend of circumferential crescents and normal glomeruli were the key factors predicting the treatment response in RRT and non-RRT groups,respectively.While the the need of RRT and proteinuria were the main factors affected long-term renal survival.Our results indicate that renal histology is required prior to the treatment decisions.更多还原