肾演粉样变性的临床、病理及免疫病理

分析8例肾淀粉样变性的临床、病理及免疫病理特点，并在国内首次用肾组织免疫球蛋白κ，λ轻链、血清淀粉A蛋白（SAA）染色及高锰酸钾试验辅助分型。结果显示：①淀粉样变性多见于50岁以上患者，常表现为多系统损害拦有典型肾病综合征；②肾脏病理改变以“肾小球系膜区结节状硬化和非增殖、非炎症性变化”为特征。免疫病理常呈多种免疫球蛋白、补体共同沉积的“满堂红”现象；③7例AL与1例AA型演粉样变的肾脏病理改变类似，但前者有κ，λ轻链的沉积，后者可检出SAA。高锰酸钾试验阴性3例均为AL型，阳性1例为AA型。     

肾淀粉样变性的临床及免疫病理

肾淀粉样变性的临床及免疫病理尹广，黎磊石，刘志红，周虹，张少凌，宋岩我们分析８例肾淀粉样变性的临床、病理及免疫病理特点，并在国内首次用肾组织免疫球蛋白轻链、血清淀粉Ａ蛋白染色以及高锰酸钾试验辅助分型，旨在加深认识、提高诊断水平。材料与方法８例患者均经...     

肾淀粉样变性病理诊断的体会

淀粉样变性可以分为系统性和局灶性两类.系统性淀粉样变性包括免疫球蛋白轻链（AL）、血清淀粉样A物质（AA）、家族性、衰老的系统性淀粉样变性和透析相关的淀粉样变性.局灶性淀粉样变则包括：局灶的AL淀粉样变以及与帕金森病和快速进展性疾病相关的阿尔茨海默病,克雅病;此外2型糖尿病也属此类.最常见的累及肾脏的淀粉样物质是AL、AA以及家族性淀粉样变性.笔者从肾活检病理角度谈谈对肾淀粉样变性诊断的体会.     

肾淀粉样变性诊断治疗的临床体会

淀粉样变性是一种全身性疾病,其临床与病理表现是由淀粉样物质沉积于全身各脏器所致,肾脏为最常见受累器官之一.该病并不少见,诊断和治疗上有其特殊之处,在此,我们谈谈多年来在肾淀粉样变（AL型）诊治中的临床体会,和大家共同探讨.     

表现为心肾联合损害的淀粉样变性1例

正1病例资料患者,男性,64岁,农民,因"间断胸闷气短半年余,加重5 d"于2016年3月28日入住首都医科大学附属北京友谊医院医疗保健中心内科。患者半年余前无明显诱因出现活动后胸闷、气短症状,伴心悸、乏力、食欲减退、双下肢水肿、尿色深、尿中泡沫多。就诊于外院,诊断为慢性肾功能不全,给予利尿治疗后症状缓解。曾于我院门诊就诊,诊断为心功     

轻链型心肌淀粉样变性病人的临床特征及预后相关因素分析

目的研究轻链型心肌淀粉样变性(AL-CA)病人临床特征及预后的相关因素、早期诊断及治疗,从而改善预后,延长生存时间。方法回顾性分析江苏省人民医院84例诊断为轻链型心肌淀粉样变性病人临床资料,采用Cox回归模型分析影响预后的危险因素。结果共纳入病人84例,其中男55例,女29例,男女比例为1.9∶1;年龄(59.98±7.50)岁。化疗组51例,死亡25例;非化疗组33例,死亡27例。使用Kaplan-Meier方法分析化疗对病人生存情况的影响,化疗组较非化疗组生存时间长(中位生存时间分别为38个月与5个月,P<0.001)。对53例行血清游离轻链(sFLC)检测的病人以血清游离轻链差值(dFLC)中位数189.98 mg/L为界点,分为高dFLC组和低dFLC组,高dFLC组舒张早期二尖瓣血流速度与舒张晚期二尖瓣血流速度比值(E/A)>2的病人比例高于低dFLC组(19.2%与55.6%,P<0.01);Cox单因素分析提示dFLC≥189.98 mg/L、心功能分级≥Ⅲ级、E/A>2、心律失常、低血压为影响生存的危险因素,但采用Cox风险比例模型进行多变量分析时,仅E/A>2、低血压是影响病人生存的危险因素。结论心肌淀粉样变性病人临床表现缺乏特异性,预后差,早期诊断至关重要。     

心脏淀粉样变性的诊断进展

淀粉样变性是由于淀粉样蛋白沉积在细胞外基质,造成沉积部位组织和器官损伤的一组疾病,出现心脏受累时即为心脏淀粉样变性,该病病情重、进展快、治疗困难、病死率高,但临床少见且识别率低。本文着重叙述其诊断手段和相关进展,并对诊断流程进行了归纳,以协助临床了解并正确诊断该病,使患者获得及时治疗并从中获益。     

伴多核巨细胞浸润的轻链型肾淀粉样变性

64岁男性患者,临床表现为肾病综合征,无高血压及肾功能损害,血免疫固定电泳检查示λ型IgA单克隆免疫球蛋白条带,血游离轻链检查示κ/λ比值下降;骨髓流式细胞学见4.52%单克隆增生的浆细胞,外院肾活检诊断轻链型肾淀粉样变性。患者化疗后临床达非常好的部分缓解,经重复肾活检后诊断为罕见的伴多核巨细胞浸润的轻链型肾淀粉样变性。     

肾淀粉样变性病32例临床病理特点及误漏诊分析

目的 从多系统受累临床表现和病理分型方面了解肾淀粉样变性病特点,分析临床误漏诊情况及原因.方法 回顾性分析北京大学第一医院1999年1月至2006年1月肾内科确诊32例肾淀粉样变性患者的临床资料,应用免疫组织化学方法对进行淀粉样蛋白A重新染色分型.结果 90.6%患者发病年龄大于40岁.87.5%的患者有超过2个系统受累.65.6%的患者曾经被误诊为原发性肾病综合征.免疫组织化学方法示仅1例患者AA蛋白阳性,19例行免疫荧光检查,K轻链阳性10.5%,λ轻链阳性15.8%,两者均阳性占10.5%,两者均阴性占63.2%.结论 肾淀粉样变性病常累及多系统,临床表现多样,误诊率高.中老年肾病综合征患者出现体重下降、巨舌、肝、脾肿大和血压下降是可靠的线索,应常规行血、尿免疫固定电泳检查.确诊AA型需依靠免疫组织化学AA蛋白染色.     

轻链型心肌淀粉样变性患者的临床特征及预后相关因素

目的 探讨轻链型心肌淀粉样变性（AL-CA）患者的临床特征、治疗反应、以及对预后有影响的危险因素。方法 分析2016年9月～2021年9月曾于我院住院治疗的65例AL-CA患者的临床资料。依据治疗方案的不同,将使用硼替佐米联合地塞米松（BD）方案的患者记为BD组（n=38）,将使用环磷酰胺、沙利度胺联合地塞米松方案或马法兰联合地塞米松方案的患者记为非BD组（n=27）。收集患者入院时的症状、体征、相关检查检验结果与化疗方案等信息,比较采取不同化疗方案下患者的治疗反应与生存状况,采用COX风险比例模型寻找预测患者生存的独立危险因素。结果 与非BD组相比,BD组Mayo 2012 IV期患者比例较高,血清游离轻链差值较高（P<0.01）。两组患者心电图检查主要表现均为导联低电压,超声心动图检查主要表现均为舒张功能障碍以及室间隔或左室壁增厚,无组间统计学差异。在3个月时,BD组与非BD组可评估血液学反应的分别有24例与17例患者,取得非常好的部分血液学缓解及以上血液学反应的患者分别占71%与35%(P<0.05)。通过COX风险比例模型,发现碱性磷酸酶、D-二聚体、血肌酐、N端脑...     

Systemic AA amyloidosis as a unique manifestation of a combined mutation of TNFRSF1A and MEFV genes

Abstract

We report the case of a 22-year-old Caucasian woman presenting with a new-onset nephrotic syndrome with normal renal function during the 35th week of pregnancy. AA (secondary) amyloidosis was further diagnosed at the renal biopsy. Extensive genetic testing revealed that the patient was heterozygous for both TNFRSF1A p.R92Q and MEFV p.M694I mutations leading to an autoinflammatory syndrome characterized by amyloid deposition as the sole manifestation.     

Severe intrahepatic cholestasis,erythrocytosis and hypoglycemia: Unusual presenting features of systemic AL amyloidosis

We report the case of a 68-year-old African woman who presented with jaundice, hepatomegaly and anasarca. Clinical investigation disclosed severe intrahepatic cholestasis, nephrotic syndrome, erythrocytosis and hypoglycemia. Diagnosis of systemic AL amyloidosis was established by percutaneous liver biopsy. Bone marrow biopsy showed 32% of myeloma cells. The patient started treatment with melphalan and prednisolone, but liver function deteriorated and she died in hepatic failure complicated by septic shock three weeks after the diagnosis. We present possible explanations for the unusual clinical and laboratory findings, which required a multidisciplinary approach and posed challenging problems in differential diagnosis and management.     

Etanercept treatment of renal amyloidosis complicating rheumatoid arthritis

Rheumatoid arthritis and juvenile arthritis represent the commonest diseases complicated by AA amyloidosis in developed countries. Up to 5% of patients with rheumatoid arthritis will develop AA amyloidosis, with renal failure being the commonest cause of mortality. To date, treatment of this condition has focused on suppressing the underlying inflammatory condition with drugs such as cyclophosphamide and chlorambucil, but both these drugs are associated with myelotoxicity, leukaemia and sterility. Tumour necrosis factor-alpha (TNF-alpha) is thought to be involved in amyloid deposition. The efficacy of anti-TNF-alpha therapy (etanercept) in the treatment of renal amyloidosis complicating rheumatoid arthritis is demonstrated here and the current scientific data on this subject are presented.     

Secondary amyloidosis in Indigenous Australians

Secondary amyloidosis (AA) is an established consequence of many chronic inflammatory conditions. In the developed world, it is most often the result of rheumatological disease. However, the relative frequency of underlying causes may be different in indigenous populations. We present a case series of three remote‐living, Indigenous Australians found to have pathologically confirmed amyloidosis and renal impairment at diagnosis. The presence of an underlying inflammatory condition was unclear in two cases. The remaining case had established bronchiectasis and suffered rapidly progressive renal impairment at a young age.     

Amyloid precursors and amyloidosis in rheumatoid arthritis

Amyloidosis refers to the extracellular accumulation of amyloid fibrils, derived from a circulating precursor, in various tissue and organs. The most common form of amyloidosis worldwide is that which occurs secondary to chronic inflammatory disease, particularly rheumatoid arthritis. The precursor molecule is serum amyloid A (SAA), an acute phase reactant, which can be used as a surrogate marker of inflammation in many diseases. SAA has a number of immunomodulatory roles, can induce chemotaxis and adhesion molecule expression, has cytokine-like properties and can promote the upregulation of metalloproteinases. It enhances the binding of high density lipoprotein to macrophages and thus helps in the delivery of lipids to sites of injury for use in tissue repair. It is thus thought to be an integral part of the disease process. Moreover, elevated levels of SAA over time predispose to secondary amyloidosis. Pathogenic factors underlying this disease are outlined along with guidelines for diagnosis and management.     

Systemic AA amyloidosis induced by oral contraceptive-associated hepatocellular adenoma: a 13-year follow up

Abstract: We report a case of a woman who showed hepatic and renal AA amyloidosis with a liver adenoma associated with the use of oral contraceptives. A nephrotic syndrome secondary to the renal amyloidosis underwent complete remission 7 years after the withdrawal of oral contraceptive therapy. Twenty-nine months after the initial presentation, the patient was admitted with acute upper abdominal pain and abdominal tenderness. The abdominal ultrasound revealed a subphrenic fluid collection, and a presumptive diagnosis of a ruptured hepatic adenoma was made. The liver adenoma diminished from 8 cm to 1 cm over a 13-year follow up after the discontinuance of oral contraceptive therapy.     

Serum amyloid A serum concentrations and genotype do not explain low incidence of amyloidosis in Hyper-IgD syndrome

Background.?Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessively inherited disorder characterized by recurrent episodes of fever and inflammation. Unlike other chronic inflammatory conditions, amyloidosis is very rare in HIDS. For deposition of amyloid of the AA type, high concentrations of SAA are a prerequisite, together with certain SAA1 gene polymorphisms. The SAA1.1 genotype predisposes for amyloidosis, while SAA1.5 genotype exerts a protective effect.

Aim of the study.?To determine if SAA concentrations and SAA1 gene polymorphisms could explain the virtual absence of amyloidosis in HIDS patients.

Methods.?We measured SAA and CRP concentrations in serum of 20 HIDS patients during an attack and during the asymptomatic phase. Genotype of SAA1 gene was determined in 60 HIDS patients.

Results.?SAA serum concentrations during attacks were very high (median 205?mg/l; range 75–520?mg/l, normal?<?3.1?mg/l). During attack-free periods 45% of patients still had elevated SAA concentrations. The distribution of the genotype of SAA1 gene in HIDS was similar to healthy controls (SAA1.1 0.41 vs. 0.50 p?=?0.32).

Conclusion.?Patients with HIDS have high SAA during attacks and show sub-clinical inflammation when asymptomatic. The low incidence of amyloidosis cannot be explained by a predominance of non amyloidogenic SAA related genotypes.     

东北地区147例成人原发性肾病综合征的临床病理研究

本文报告了东北地区147例成人原发性NS的临床病理观察。主要病理类型为MCNS(31.3％)和MsPGN(30.6％)。主要发病诱因是上呼吸道感染,这可能与气候、环境影响有关。91.2％病例血清α_2球蛋白增高,81％病例血IgG降低,75.5％病例血沉增快。作者认为此三项指标对NS有诊断意义。全部病例中完全缓解和部分缓解率分别为46.3％和31.3％,其中MCNS为67.4％和28.3％,MsPGN为55.6％和33.3％,FSGS为23.5％和52.9％.113例经过4.57±2.14年随访,未见有恶性疾病发生。本文结果显示,血栓栓塞性疾病可能成为NS患者的主要死亡原因.     

Successful use of Tocilizumab in a patient with nephrotic syndrome due to a rapidly progressing AA amyloidosis secondary to latent tuberculosis

AA (secondary) amyloidosis is one of the most severe and uncommon complications of several rheumatic disorders and chronic infections such as tuberculosis (TB). Successful treatment depends on the control of the underlying inflammatory process, what can lead to an improvement or a regression in organ dysfunction. If the disorder persists, it has been reported in some cases of AA amyloidosis secondary to rheumatic diseases, that the use of biologic therapy is so far the only opportunity to reduce the development of AA amyloidosis and to reverse established deposits. We report herein a case of a latent TB infection complicated by a life-threatening AA amyloidosis presented as nephrotic syndrome. After an adequate antituberculostatic treatment, AA amyloidosis remained active and Tocilizumab (TCZ) was started with a dramatic resolution of the proteinuria, stabilization of the amyloid deposits and improvement in general condition.