特发性膜性肾病合并其他肾脏病理损害的临床病理特征分析

目的 旨在研究特发性膜性肾病合并其他肾脏病理损害患者的临床及病理特征。方法 收集2015年1月~2018年6月郑州大学第一附属医院肾内科经皮肾脏穿刺活检术诊断为特发性膜性肾病(IMN)的1102例患者资料,利用SPSS 21.0统计学软件分析单纯IMN组(单纯IMN 953例)和IMN合并其他肾脏病理损害组(IMN+OPI 149例)病理及临床表现特征。结果IMN+OPI患者男性比例更高,年龄更大,BUN、Scr、24h尿蛋白水平以及PLA2R-Ab效价均显著增高(P＜0.05),而Hb、Alb水平显著降低(P＜0.05);荧光染色IgA的阳性比例显著高于单纯IMN组(P＜0.05),肾小管间质病变、肾小血管病变积分显著高于单纯IMN组(P＜0.05);两组之间采用激素或免疫抑制剂治疗的比例比较差异无统计学意义(P＞0.05)。1102例特发性膜性肾病患者中,单纯IMN组占86.48%;合并肾小管/间质损伤(IMN+RTI)组占6.72%;合并缺血性肾损伤(IMN+IRI)组占2.81%;合并IgA肾病(IMN+IgAN)组占2.36%;合并糖尿病肾病(IMN+DN)组占1.63%。合并不同类型肾脏病理损害的IMN患者与单纯IMN患者比较,多数类型的BUN、Scr、24h尿蛋白水平显著增高(P＜0.05),肾小管间质病变及肾小血管病变较重(P＜0.05),但使用激素或者免疫抑制剂方面比较,差异无统计学意义(P＞0.05)。结论 IMN合并其他肾脏病理损害中,IMN合并肾小管/间质损伤最常见;与单纯IMN比较,IMN合并其他肾脏病理损害患者病情更重,为临床诊治提供了更多线索。     

不同年龄特发性膜性肾病临床及病理分析

目的比较青年、中年、老年人特发性膜性肾病(IMN)的临床病理特点,探讨它们之间的异同点。方法 79例IMN患者,按年龄分为青年(15~29岁)组(21例)、中年(30~59岁)组(41例)、老年(60~75岁)组(17例),对其临床病理资料进行回顾性分析。结果 3组临床分型均以肾病综合征为主,各组临床分型构成比差异无统计学意义(P>0.05)。老年组高血压发生率、血肌酐明显高于青年组和中年组,eGFR明显低于青年组、中年组。青年组血尿发生率明显高于中年组和老年组。青年组病理分期以Ⅰ期膜性肾病为主(85.7%),明显高于其他两组;同时系膜细胞增生、"满堂亮"现象及电镜下电子致密物多部位沉积百分比均明显高于其他两组。老年组肾小管间质半定量积分、小血管病变积分明显高于其他两组。结论不同年龄组的IMN既有相同点,也有不同点。熟悉它们的异同点,将有助于IMN诊治水平的提高。     

特发性膜性肾病伴高尿酸血症患者的临床特征及病理特点

目的:探讨特发性膜性肾病(IMN)伴高尿酸血症患者的临床特征及病理特点.方法:选取2015年1月—2019年12月我院收治的150例特发性膜性肾病(IMN)患者作为观察对象,按照高尿酸血症的检测标准分为血尿酸正常组(106例)和高尿酸血症组(44例);分析两组患者性别、年龄、病程、高血压情况及并发症发生情况等一般资料;...     

免疫指标阳性的不典型膜性肾病临床与病理分析

目的 比较免疫指标阳性的不典型膜性肾病(AMN)与特发性膜性肾病(IMN)的临床特征与病理改变,以助于鉴别诊断和指导治疗。方法 回顾性分析2012年1月~2019年9月肾内科住院临床资料完整患者,其中肾穿刺病理诊断为AMN伴抗核抗体(ANA)等免疫指标阳性的患者28例(AMN组),肾穿刺病理诊断为膜性肾病的IMN患者123例(IMN组),比较两组患者一般资料及临床表现、实验室检查结果、肾脏病理学结果。结果 免疫指标阳性的AMN组患者和IMN患者比较,AMN组发病年龄轻,女性比例高,镜下血尿明显,补体C3、C4降低,伴有白细胞计数降低等血液系统异常,免疫荧光包含C1q的多种免疫复合物沉积比例升高,IMN患者PLA2R阳性比例高。结论 免疫指标阳性的不典型膜性肾病,病理类型类似于Ⅴ型狼疮,临床多表现为肾病综合征,ANA、抗SSA抗体、抗SSB抗体等免疫指标阳性率高,病理免疫荧光多种免疫复合物沉积,特别伴有“满堂亮”,高度提示狼疮性肾炎,应早期给予积极治疗。     

特发性膜性肾病的治疗

特发性膜性肾病（IMN）是成人原发性肾小球疾病的常见病理类型之一。典型病理特征为上皮下免疫复合物沉积致毛细血管基底膜增厚。目前IMN的治疗颇有争议,本文对其治疗现状做一综述。1特发性膜性肾病的临床特点膜性肾病（MN）临床上主要表现为肾病综合征或大量蛋白尿,70%-80%呈肾病程度蛋白尿,5%-10%伴有肾功能不全,高血压及血尿发生率较少。MN常见于成人,约占成人肾病综合征的33%,儿童患者少见。     

中老年与青年特发性膜性肾病临床病理特点分析研究

目的 探讨不同年龄段的特发性膜性肾病(IMN)患者临床病理特点。方法 回顾性分析2014年1月~2020年3月首都医科大学附属北京天坛医院经肾活检确诊并排除继发因素的IMN患者,根据年龄分为青年(≤35岁),中年(36~59岁)和老年(≥60岁)组。比较3组之间的临床和病理资料。结果 共有79 例患者纳入研究。与青、中年组IMN患者比较,老年组患者病程长(P=0.037),合并高血压(P=0.028)、糖尿病比例高(P=0.000),肾小球滤过率低(eGFR)(P=0.000),血红蛋白低(P=0.001)。3组收缩压、舒张压、24h尿蛋白定量、血尿、尿素氮、尿酸、白蛋白、甘油三酯、总胆固醇比较,差异无统计学意义。病理方面,与中青年组IMN患者比较,老年组肾小球硬化比例高,差异有统计学意义(P=0.048)。老年组肾小管萎缩、肾小管间质纤维化、炎性细胞浸润比例均高于中、青年组,但差异无统计学意义(P＞0.05)。结论 不同年龄段的IMN 患者临床病理特点差异有统计学意义,老年IMN患者起病时临床病理表现重的比例增加。     

膜性乙型肝炎相关性肾炎与特发性膜性肾病临床比较研究

目的探讨膜性乙型肝炎病毒相关性肾炎（HBV—MN）的临床病理特点及诊治方法。方法回顾性分析比较26例HBV—MN和32例特发性膜性肾病（IMN）临床表现、病理及诊治的异同。结果（1）两组发病年龄、血尿值、HT率、血肌酐值及eGFR较HBV—MN组均明显低于IMN组,差异有统计学意义（P〈0．05或〈001）。（2）两组患者均以I、II期膜性肾病常见,且HBV—MN组表现为多种免疫复合物、多部位高强度沉积,而IMN组以IgG、C3在上皮下和基底膜高强度沉积。（3）治疗方法间比较无明显不同。结论HBV—MN多发于男性中、青年,主要临床表现为肾病综合征、慢性肾炎综合征合并肾病综合征;病理特征为多种免疫复合物、多部位、高强度沉积,以I、II期膜性肾病常见;激素、霉酚酸酯及拉米夫定临床治疗均有效。     

118例特发性膜性肾病临床及病理特点分析

目的 总结特发性膜性肾病(idiopathic membranous nephtopathy,IMN)的临床及病理特点。 方法 回顾性分析浙江省人民医院2013年1月-2016年10月经肾活检确诊的118例IMN患者的完整临床及病理资料。 结果 118例IMN患者中男性69例(58.5%),女性49例(41.5%);年龄(51.7±12.3)岁,中老年患者占74.6%;蛋白尿0.07~27.60 g/24 h,其中≥ 3.50 g/24 h者69例(58.5%);肾病综合征76例(64.4%);血尿102例(86.4%);肾小球滤过率(eGFR)≥ 60 ml/(min·1.73 m2)者102例(86.4%),<60 ml/(min·1.73 m2)者16例(13.6%)。与女性比较,男性患者血清中肌酐、尿素氮及尿酸水平均较高,差异均有统计学意义。随年龄增长,肾功能下降更明显,肾小管间质损伤程度加重,肾小球球性硬化患者更多,小动脉病变更明显;肾小球病理分期以Ⅰ、Ⅱ期为主,占97.5%。 结论 男性、年龄大、尿酸水平高、尿蛋白量多者,肾功能减退多见,肾小管间质病变重,小动脉病变明显,故宜尽早就诊并行穿刺活检。      

膜性肾病患者肾组织M型磷脂酶A2受体1抗原及其抗体的表达差异

目的 探讨肾组织M型磷脂酶A2受体1(PLA2R1)抗原及其抗体在膜性肾病(MN)患者中的表达水平.方法 选取经肾活检证实的特发性MN(IMN)58例、乙型肝炎病毒相关性MN(HBV-MN) 15例、V型狼疮性肾炎(V-LN) 17例.采用间接免疫荧光法检测肾组织PLA2R1抗原,并与IgG4共定位.同时检测上述MN患者血清抗PLA2R1抗体.分析肾组织PLA2R1抗原及其抗体在MN中的表达差异,以及PLA2R1阳性与阴性患者临床资料的差异.结果 VLN及HBV-MN患者肾组织及血清中均未发现PLA2R1抗体;在81.03％ IMN患者肾组织检测到PLA2R1抗原,70.69％ IMN患者血清中检测到PLA2R1抗体,PLA2R1抗原与IgG4共定位,均沿肾小球毛细血管袢呈细颗粒状沉积.PLA2R1抗原阳性患者24 h尿蛋白定量高于阴性患者(P＜0.05),并且血清清蛋白低于阴性患者(P＜0.05).结论 肾组织PLA2R1抗原在IMN的诊断中敏感性及特异性均较高,且表达与临床病情严重性明显相关.     

膜性肾病的多靶点治疗一例

膜性肾病是成人肾病综合征的常见原因,根据临床和病理可分为特发性膜性肾病(IMN)和继发性膜性肾病。目前,关于IMN的最佳治疗方案一直存在争议,糖皮质激素和烷化剂或钙调神经磷酸酶抑制剂(CNIs)联合治疗方案在临床上广泛应用,但由于长期应用烷化剂的毒性不良反应,以及CNIs存在肾毒性和高复发的风险,抗CD20生物治疗及利妥昔单抗(RTX)作为一线治疗方法在临床逐步普及。在临床工作中需密切结合患者的实际情况,选择个体化的治疗方案。现将1例IMN患者经多靶点免疫抑制治疗取得较好疗效的资料汇报如下。     

不典型膜性肾病与特发性膜性肾病的临床特征与病理改变比较

目的比较不典型膜性肾病（AMN）与特发性膜性肾病（IMN）的临床特征与病理改变,以助于鉴别诊断。方法选取临床资料完整、初发初治AMN患者79例（AMN组）,IMN患者134例（IMN组）。比较两组患者一般资料及临床表现、实验室检查结果、肾脏病理学检查结果。结果与IMN组比较,AMN组患者年龄较小、肾病综合征发生率较高（均P＜0.05）。两组患者性别、体重、BMI及高血压、急性肾损伤、血栓和栓塞发生率比较差异均无统计学意义（均P＞0.05）。与IMN组比较,AMN组患者尿RBC、24h尿蛋白定量、尿NAG、血清D-二聚体较高,血清白蛋白较低（均P＜0.05）。两组患者血清TC、TG、血尿酸、Cr、ANA阳性率、HBsAg阳性率、HBeAg阳性率、IgG、IgA、IgM、C3、C4、CRP、eGFR比较差异均无统计学意义（均P＞0.05）。两组患者肾小球硬化比例比较差异无统计学意义（P＞0.05）,但AMN组患者肾小管间质急性、慢性病变均较重（均P＜0.05）。AMN组患者肾组织IgA、IgM、C4、C1q、IgG1、IgG2、IgG3阳性率均高于IMN组（均P＜0.05）,IgG4、PLA2R阳性率均低于IMN组（均P＜0.05）。AMN患者在系膜区、基底膜部位比IMN患者更易出现电子致密物沉积（P＜0.05）。结论AMN患者在临床特征和病理改变上均与IMN存在差异,提示AMN的发病机制及疾病预后可能不同于IMN。     

内质网应激与膜性肾病

内质网(endoplasmic reticulum,ER)是调节蛋白质合成、折叠及组装的重要场所。各种原因如ER中Ca2+缺乏均可引起ER功能紊乱,使蛋白质从ER向高尔基体的转运受阻[1],最终引发内质网应激(endoplasmic reticulum stress,ERS)。细胞通过激活未折叠蛋白反应(the unfolded protein response,UPR)保护ERS引起损伤的细胞,强烈或持久的ERS又可启动UPR的促凋亡信号。肾病尤其是膜性肾病(membranous nephropathy,MN)的发生发展与ERS密切相关,文中主要阐述ERS在MN发病机制中的作用。     

Podocyte-related proteins in membranous nephropathy progression

Membranous nephropathy （MN） is the most common cause of nephrotic syndrome in adults.The renal biopsy is the gold standard for the disease diagnosis,but is invasive.M-type phospholipase A2 receptor （PLA2R） on human podocytes could serve as the target for podocytopathic antibodies （anti-PLA2R）.1 Patients with iMN （70%-80%） were found the circulating antibodies against PLA2R.1 And the podocyte-secreted angiopoietinlike-4 （Angptl4） could be another key role in nephrotic syndrome3.     

Cyclosporin A treatment for idiopathic membranous nephropathy

Objective To evaluate the efficacy of cyclosporin A (CSA) in the treatment of idiopathic m embranous nephropathy (IMN), a prospective controlled clinical study was performed.Methods This study included a group of 30 IMN patients, among them 15 were treated with CSA and 15 with captopril (CAP).The diagnosis of IMN was mad e with exclusion of secondary forms of membranous nephropathy by extensive clini cal and pathological studies.No patients received steroids or cytotoxic agents for six months prior to enrollment.In the CSA group, CSA was given at an init ial dosage of 5 mg·kg(-1)·d(-1), gradually tailed off over the firs t three months and maintained at 2 mg·kg(-1)·d(-1) for 12 months. In the CAP group, CAP was given at a dosage of 37.5 mg/day. Results In the first three months, 6 (6/15)complete remissions (CR) and 2 (2/15) partial remissions (PR) were observed in the CSA group while only 2 (2/15) PRs were ob served in the CAP group.Before the end of the 15-months, 8 patients in the C SA group experienced CR and 4 patients experienced PR.One CR patie nt relapsed as the dosage of CSA was reduced, so 7 patients remained in CR at th e end of the first 15-months.No additional CR or PR was observed in the CA P group during late follow-up.At the last visit (an average follow-up time o f 44 months) in the CSA-group, another 2 CR patients had relapsed and 1 CR pati ent shifted to PR after stopping the CSA treatment, so 4 CR and 5 PR remained i n t he CSA group.In the CAP group, 3 spontaneous CRs occurred beyond 1.5 year’s f ollow-up, with 3 CR and 2 PR at the last visit.No difference was found betwee n the averages of the initial and the last serum creatinine levels in either gro up.No serious adverse effects were found during CSA treatment.Re-biopsy dat a of three patients responsive to CSA treatment showed that no pathological impr ovement of glomerular basement membrane was observed, even in cases at remission .Tubulointerstitial fibrosis was found in 1 relapsed CR patient, whose serum c reatinine increased above the normal range, but not in the other 2 patients whos e serum creatinine remained in the normal range.Conclusions CSA therapy at a dosage of 5 mg·kg(-1)·d(-1) is effective in inducing remission of nephrotic syndrome in adult IMN patients within three m onths, with a response rate of 80%.A relatively high rate of relapse (50%) was observed within 2 years after the withdrawal of CSA treatment.     

膜性肾病的中医药研究进展

膜性肾病属本虚标实证,脾肾两虚为本,湿热、瘀血为标,湿热胶着成瘀、痰瘀互结是发病的重要病机环节,治疗上应在辨证的基础上强调活血清利。雷公藤具有抗炎、抑制免疫、保护足细胞等多靶点效应,具有良好的应用前景。从中医药治疗膜性肾病的临床实践及研究进展证明：祛风通络、益气清利活血法治疗膜性肾病具有可行性。     

Cyclosporine A in treatment of membranous lupus nephropathy

Objective To investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN).Methods Twenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg·kg-1·d-1 for 3 months, with a 1mg·kg-1·d-1 reduction every month and then maintained at a dosage of 2 mg·kg-1·d-1. The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of &lt;0.4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement &gt;50% of baseline value and a serum albumin value of 30-35 g/L, without SLE activity. No response was defined as having a Upr decrement &lt;50% of baseline value and &gt;2.0 g/d, or as a deterioration of renal function, or as having active SLE. Results One patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6-36 months (mean 16.8±8.4 months). The mean starting dosage of CsA was 4.7±0.5) mg·kg-1·d-1 and the trough level of the whole blood CsA was 248±110) μg/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17.4% (3rd month), 21.7% (6th month), 40% (12thmonth), 88.9% (18th month) and 100% (24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the patients after withdrawing CsA for 4-24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6-24 months. Conclusions CsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment.     

他克莫司治疗特发性膜性肾病临床疗效分析

目的 探讨他克莫司治疗特发性膜性肾病（IMN）临床效果。方法 根据患者治疗意愿分为观察组28例,对照组16例;观察组采用他克莫司治疗,对照组采用激素联合环磷酰胺治疗。测定两组患者治疗前及治疗后3个月、6个月24 h尿蛋白定量、血肌酐、血尿素、血白蛋白和抗 M 型磷脂酶A2受体1的抗体(PLA2R-Ab)。两组患者均在治疗6个月后评价治疗效果。结果 两组患者在治疗3个月、6个月后24 h尿蛋白定量、血白蛋白、三酰甘油、胆固醇均有明显改善,差异均有统计学意义（P<0.05);并且观察组较对照组改善更明显（P<0.05）;观察组治疗6个月后血肌酐、尿素较治疗前有升高,差异均有统计学意义（P<0.05）;对照组空腹血糖、白细胞治疗3个月、6个月后较治疗前升高,差异有统计学意义（P<0.05）。两组患者治疗3个月、6个月后血PLA2R-Ab均有明显降低,差异均有统计学意义（P<0.05);并且与治疗3个月比较,两组治疗6个月后血PLA2R-Ab降低更明显（P<0.05）;观察组治疗后3个月、6个月后均较对照组同时间降低更明显（P<0.05）。治疗后6个月,观察组缓解率85.7%,对照组缓解率68.8%,缓解率差异有统计学意义（P<0.05）。观察组中3例患者出现血肌酐轻度增高,1例牙龈增生;对照组3例血糖升高,2例恶心呕吐。结论 他克莫司治疗IMN效果明显,不良反应轻微,明显降低血PLA2R-Ab。     

Case of generalised myasthenia gravis with membranous nephropathy

We report a 40-year old woman with bilateral partial ptosis, complete external ophthalmoplegia, and weakness and fatiguability of upper limbs. She was on treatment for hypertension for 5 months at the time of admission. She was found to have generalised myasthenia gravis and membranous nephropathy with end-stage renal disease. Her symptoms and signs improved within 2 months on treatment with neostigmine and prednisolone. It is postulated that either thymic hyperplasia or the subclinical stage of a thymoma may be the underlying aetiological factor in this patient.