轻链沉积病患者临床病理特征

目的:阐明轻链沉积病(LCDD)患者的临床病理特征、预后及其相关危险因素。方法:回顾分析LCDD患者的临床、病理及随访资料,应用Kaplan-Meier法分析肾脏存活率,COX回归模型分析预后危险因素。结果:观察45例LCDD患者,肾活检时平均年龄50.8岁,男∶女1.6∶1。11例(24.4%)患者同时确诊多发性骨髓瘤(MM)。患者高血压、贫血、肾功能不全、尿蛋白定量≥3.5 g/24h和镜下血尿的发生率分别为80.0%、95.6%、95.6%、44.4%和82.2%。血清单克隆免疫球蛋白条带阳性者为26.2%,血清轻链κ/λ1.65者占84.4%,31.1%为显著异常(8),33.3%患者补体C3降低。80%的患者组织学改变为肾小球结节样病变,20%为肾小球轻至中度系膜增生,53.3%患者肾小管间质慢性病变重度,77.8%患者光镜下存在轻链相关动脉病变。免疫荧光提示κ轻链沉积占93.3%,沿肾小管和肾小球基膜线样分布,系膜区团块状分布。5例患者失随访,余40例患者平均随访22.1个月,共26例(65.0%)进入ESRD,平均肾脏存活时间为33.8月。单因素和多因素COX回归分析显示,肾活检时血清肌酐(SCr)、尿视黄醇结合蛋白(RBP)是进展至ESRD的重要危险因素,未发现其他临床及病理指标与肾脏预后相关。结论:LCDD多发于中年男性,临床表现高血压、蛋白尿、肾功能不全、贫血,血清轻链比值异常较血清免疫固定电泳是更为敏感的诊断提示。肾小球结节病变、肾小管基膜增厚,电子致密物沿肾小球基膜内侧缘和肾小管基膜外侧缘沉积是主要病理表现。轻链沉积以κ型为主。LCDD患者预后差,SCr、RBP是影响预后的独立危险因素。     

伴单克隆IgG1沉积的增生性肾小球肾炎

61岁女性,病程10个月,临床表现尿检异常、低补体血症伴贫血、血游离轻链比值异常,免疫固定电泳见Ig G-λ单克隆免疫球蛋白条带,肾脏体积增大,骨髓浆细胞7. 5%、未见原始和幼稚浆细胞,肾活检示膜增生性肾小球肾炎(结节样病变),Ig G1++、λ轻链+颗粒状沉积于系膜区及血管袢,Ig G2、Ig G3、Ig G4、κ轻链阴性;诊断为伴单克隆Ig G1沉积的增生性肾小球肾炎。给予沙利度胺联合地塞米松治疗1年,蛋白尿完全缓解,补体上升,血游离轻链比值恢复正常,血清M蛋白转阴。     

单克隆免疫球蛋白病相关C3肾炎的临床病理分析

目的:了解单克隆免疫球蛋白病相关的C3肾炎的临床病理特征。方法:回顾性分析2004年3月至2015年5月南京军区南京总医院肾脏科经肾活检病理诊断为C3肾炎的患者,筛选出血清免疫固定电泳见单克隆条带者,统计其临床及病理资料。结果:(1)一般资料:C3肾炎患者共有38例,其中行血清免疫固定电泳检查者16例。血清单克隆免疫球蛋白阳性者7例,男性5例、女性2例,肾活检时年龄44~65岁,病程3~67月。肾脏损害临床表现为肾病综合征4例,多形型血尿者6例,血清肌酐升高3例,贫血4例。(2)补体及补体相关检查:C3下降4例,C4、血清H因子均正常,C3肾炎因子及抗H因子抗体均阴性(6/6)。(3)血液学检查:单克隆免疫球蛋白种类λ型IgG 3例,κ型IgG 2例,λ型IgA 1例,κ轻链1例。血游离轻链比值异常2例。浆细胞升高2例(2/6)。(4)肾脏病理:7例免疫荧光均以C3沉积于肾小球毛细血管袢及系膜区,轻链染色阴性,光镜均呈膜增生样病变,2例伴新月体,肾小管间质病变较轻;电镜下电子致密物无特殊结构,主要沉积于内皮下及系膜区,2例内皮细胞病变明显。(5)治疗及随访:2例浆细胞异常的患者接受沙利度胺联合地塞米松治疗,其中1例肾脏病长期缓解,1例快速进展至终末期肾病;余5例患者接受雷公藤多苷和(或)糖皮质激素治疗,1例失随访,3例尿检改善,4例肾功能稳定。结论:单克隆免疫球蛋白相关的C3肾炎好发于中老年患者,组织学以肾小球膜增生样病变为主,免疫抑制治疗有一定的疗效,但治疗的关键应针对单克隆免疫球蛋白病。     

肾脏轻-重链沉积病

中年男性,病程3年,临床表现为中等量蛋白尿、少量镜下血尿、高血压、肾功能不全,伴贫血、白细胞减低,血清免疫固定电泳见λ型IgA单克隆免疫球蛋白条带,骨髓细胞学检查浆细胞比例5%。组织学改变为肾小球结节样病变,免疫荧光染色IgA及单一λ轻链均呈线状沉积于肾小球毛细血管袢及肾小管基膜,超微结构见肾小球基膜内侧缘及肾小管基膜外侧缘细沙状、高电子密度的致密物沉积。最终诊断为轻-重链沉积病(IgA-λ型)。     

多发性骨髓瘤患者肾损害临床与病理特征——附24例分析

目的　了解多发性骨髓瘤 (MM)肾损害患者临床病理特征。方法　回顾性分析经临床、病理明确诊断的 2 4例MM肾损害患者的临床病理特征。结果　MM肾损害的临床症候群以肾功能不全 (血肌酐 >177μmol/L)最为常见 (83.3% ) ,其次为肾病综合征 (12 .5 % )、无症状尿检异常 (4.17% )。病理改变以管型肾病最为常见(6 2 .0 % ,13/ 2 1例 ) ,慢性间质性肾炎、轻链沉积病、肾小球淀粉样变性和肾小球系膜增生性病变的发生率分别为14 .3% ,9.5 2 % ,9.5 2 %和 4 .76 %。血清轻链阳性率为 6 8.4 % (13/ 19例 ) ,尿中轻链阳性率为 70 .0 % (14 / 2 0例 ) ,以λ链为主。肾组织κ、λ轻链阳性检出率为 82 .3% (14 / 17例 )。管型肾病 (13例 )较非管型肾病患者 (8例 )肾功能不全更为常见 (10 0 %vs 6 2 .5 % ,P <0 .0 5 )、本 周氏蛋白阳性率更高 (5 3.8%vs 13.5 % ,P <0 .0 5 )、小管间质病变更重 (重度小管间质病变发生率 76 .9%vs 2 5 .0 % ,P <0 .0 5 )。结论　MM伴肾损害患者临床症候群以肾功能不全多见 ,病理主要表现为管型肾病。血清与尿液中轻链以λ为主。MM伴肾损害、管型肾病患者其临床表现与病理改变均有一定的特点     

重链沉积病的临床病理特点

目的:了解重链沉积病(HCDD)的临床病理特点. 方法:回顾性分析HCDD患者临床病理资料.结果:11例患者中男性4例,女性7例,肾活检时中位年龄45岁.肾脏病病程中位值8月.8例患者存在高血压(72.7％),10例患者血浆白蛋白减低,6例(54.5％)患者血清肌酐升高,10例患者伴贫血(90.9％),4/7例(57.1％)患者血清存在λ型IgG单克隆免疫球蛋白条带,5例血κ/λ比值异常升高(＞1.65),所有患者均行骨髓活检未见骨髓瘤,9例(81.8％)患者补体C3下降,7例(63.6％)补体C4下降,9例(81.8％)伴肾病范围蛋白尿,9例(81.8％)存在镜下血尿.11例患者均为γ型HCDD,光镜表现结节样病变,5例(45.5％)伴新月体形成,肾组织单纯IgG1沉积者6例,单纯IgG2沉积者1例,单纯IgG3沉积者2例,IgG1、lgG4同时沉积者1例,IgG2、IgG4同时沉积者1例. 结论:HCDD多见于中年女性,临床常见蛋白尿、高血压、肾功能不全、低补体血症及血清常伴异常的单克隆条带,肾脏病理肾小球结节性病变明显,以γ型、IgG1亚型沉积最常见.     

增生性肾小球肾炎伴微管状单克隆免疫球蛋白IgA-λ沉积

中年男性,反复发作双下肢出血性皮疹及尿检异常,首次肾活检为"肾小球系膜增生性病变伴IgA沉积",诊断为"过敏性紫癜性肾炎"。逐渐出现高血压、肾功能不全和贫血,IgA水平增高,血清免疫固定电泳见λ型IgA单克隆条带,血轻链κ/λ比例明显低下,骨髓流式细胞学检查见单克隆浆细胞株,冷球蛋白阴性。两次重复活检光镜均表现为膜增生样病变伴栓塞,免疫荧光单克隆IgA-λ沉积,电镜下肾小球系膜区、内皮下、袢腔内及浸润细胞胞质内较多特殊微管状结构物质沉积,上皮侧偶见同类物质。最终诊断为具有肾脏意义的单克隆免疫球蛋白病,增生性肾小球肾炎伴微管状单克隆免疫球蛋白沉积(IgA-λ型)。     

华氏巨球蛋白血症相关的轻链沉积病

中年男性,贫血、高黏血症、肾功能不全、尿检阴性,免疫球蛋白lgM升高、k型lgM单克隆免疫球蛋白条带,骨髓活检提示华氏巨球蛋白血症.肾脏病理组织学见弥漫肾小管萎缩,小管基膜增厚明显;间质嗜酸性细胞浸润;肾小球病变较轻.免疫荧光染色免疫球蛋白和补体染色阴性.轻链染色显示肾小球毛细血管袢、肾小管基膜、血管壁κ轻链染色阳性.电镜下见肾小球毛细血管袢基膜内侧缘、包曼囊壁、肾小管基膜外侧缘、血管壁见泥沙样电子致密物沉积.结台临床及病理,最终诊断华氏巨球蛋白血症相关的K型轻链沉积病伴急性间质性肾炎.     

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。     

轻(重)链沉积病的诊断和治疗

轻( 重) 链沉积病是一类因单克隆免疫球蛋白轻链和( 或) 重链在组织沉积所致的全身性疾病,根据沉积的成 分不同分为轻链沉积病、重链沉积病和轻重链沉积病3 种亚型。肾脏是最常累及的器官,血、尿M- 蛋白及游离轻 链检测对诊断大有帮助,确诊依靠病理。治疗目标是去除异常浆细胞克隆、减少轻链和( 或) 重链产生,化疗及大剂 量化疗加自体干细胞移植均发现可稳定肾功能、提高患者和肾存活率。获得血液学完全缓解或非常好的部分缓解 的患者可考虑肾移植。     

Light chain deposition disease. Experience in our environment

The Light chain deposition disease (LCDD) is a strange entity characterised by the deposition of only one type of light chain in the renal tubular basement membranes. It can be associated to a plasma cell dyscrasia, however, it can occur in the absence of any detectable hematological disorder and it is called idiopathic LCDD. The clinical manifestation is renal insufficiency and nephrotic proteinuria, it does not have a clearly fixed treatment and has a severe prognosis. The aim of this work is to analyse the characteristics of the LCDD cases diagnosed within our environment. Six cases were identified, all of them between 1999 and 2005, from a total amount of 640 renal biopsies performed during this period, 4 women and 2 men, average age of 57. Multiple myeloma in 3 patients were detected (50%). The acute renal failure or rapidly progressive renal insufficiency was the most frequent clinical presentation (66%) together with nephrotic proteinuria (66%). All the biopsies showed tubular basement membranes thickening and kappa chains with a linear distribution within the same. The most frequent glomerular pathological finding was the nodular sclerosing glomerulopathy (83%). In one of the cases the affectation was exclusively tubular interstitial with tubular casts. 3 patients were treated, 2 with multiple myeloma. 5 patients needed dialysis: 3 with idiopathic LCDD within an average time of 7 days from the diagnosis to its reception and 2 with myeloma, who started needing dialysis in an average of 46 days. 4 patients died, 2 of them with myeloma. The monitoring time until the death was 13 weeks for the patients with myeloma and 110 weeks for the rest. CONCLUSION: The LCDD seems to be more frequent than what has been published and it is associated to the myeloma in half of the cases. It appears together with severe renal insufficiency and the patient's and renal prognosis is poor.     

Light chain deposition disease without detectable light chains in serum or urine. Report of a case and review of the literature.

A patient presenting with a nephrotic syndrome and chronic renal failure caused by light chain deposition disease (LCDD) without detectable light chains in serum and urine is presented. Only a few patients with LCDD but without detectable light chains in serum and urine have hitherto been reported. The diagnosis was made by light-microscopic and immunofluorescent examination of a percutaneous renal biopsy. The histological differential diagnosis of LCDD includes diabetic glomerulosclerosis, renal amyloidosis and membranoproliferative glomerulonephritis. For the histological diagnosis of LCDD, immunofluorescence using anti-kappa and anti-lambda antisera is essential. Although renal involvement is a constant feature in LCDD, other sites of deposition of light chains have been reported. The absence of detectable light chains in serum or urine is discussed.     

Monoclonal gammopathy presenting as recurrent nephrotic syndrome: therapeutic implications

Most forms of renal disease associated with monoclonal gammopathy result from deposition of monoclonal immunoglobulins or their subunits in different compartments of the kidney. Renal monoclonal immunoglobulin deposition disease (MIDD) is defined by linear deposits of monoclonal light-chain components in renal basement membranes, often producing a nodular sclerosing glomerulopathy. Clinical features of renal MIDD include proteinuria, with or without renal failure, and an association with dysproteinemias. Three types of renal MIDD have been reported, namely, light-chain deposition disease (LCDD), light- and heavy-chain deposition disease (LHCDD), and heavy-chain deposition disease (HCDD). Reports on LHCDD are rare. At present, follow-up data are limited on the management of renal monoclonal protein deposition disease. We present a case of monoclonal protein deposition in the kidney containing both heavy and light chains with unique characteristics that did not conform to any of the above previous established classes. Its follow-up revealed an unusual relapsing and remitting course in response to treatment.     

轻链沉淀病肾脏损害1例报道及文献回顾

报告了１例轻链沉淀病（ＬＣＤＤ）合并多发性骨髓瘤（ＭＭ）具有典型肾脏损害的患者。临床表现为肾病综合征、肾功能损害、异常浆细胞增生、低γ血症等。肾活检病理示肾小球系膜结节、肾小管基膜增厚、免疫酶标法抗ｋ轻链阳性。ＬＣＤＤ与异常浆细胞增生有关，多合并ＭＭ，肾脏损害为其首发和突出表现，肾功能受累明显肾脏病理有特异性的改变，免疫荧光和免疫酶标法可检出轻链的沉积，是明确诊断的重要依据。     

Renal disease in multiple myeloma

Multiple myeloma is a malignant tumor of B (plasma) cells that is characterized by monoclonal immunoglobulin production. The incidence of myeloma is increasing worldwide, particularly among individuals of advanced age. Renal impairment at diagnosis is present in approximately 20% of patients with myeloma, and uremia is the cause of death in about 15%. Several renal disorders may be present in myeloma. Bence Jones cast nephropathy (BJCN), acute tubular necrosis, and “nonspecific” tubulointerstitial nephritis are related to nephrotoxic light chains in urine. Hypercalcemia potentiates the toxicity of urinary light chains. The tissue deposition of light chains leads to renal AL-amyloidosis or light chain deposition nephropathy (LCDN). In necropsy series, the incidence of BJCN, renal AL-amyloidosis, and LCDN is about 30%, 10%, and 4%, respectively. Clinically, urinary nephrotoxic light chain-associated disorders and LCDN are usually manifested in chronic or acute renal failure. The nephrotic syndrome is commonly due to renal AL-amyloidosis. Most cases of end-stage renal failure are due to BJCN and LCDN. The basic therapy of renal impairment is hydration, forced diuresis, and initiation of chemotherapy. Diphosphonates are effective new tools for the correction of hypercalcemia, and decrease the incidence of pathological fractures. In acute renal failure, plasma exchange in association with forced diuresis, dialysis, and chemotherapy may improve renal function. End-stage renal failure requires maintenance renal replacement therapy. In myeloma patients with advanced age, the limits of medical intervention should be judged individually. Particular attention should be paid to the supportive care of the patients.     

Durable hematological response and improvement of nephrotic syndrome on thalidomide therapy in a patient with refractory light chain deposition disease

Light chain deposition disease (LCDD) is a rare disease for which an optimal treatment is not yet available. Here, we report the clinical course of a 32-year-old woman with LCDD who was successfully treated with thalidomide. She presented with nephrotic syndrome. Based on the renal biopsy findings and the presence of monoclonal immunoglobulin light chains in her serum and urine, LCDD was diagnosed. Prednisolone and cytotoxic chemotherapy used for multiple myeloma proved ineffective. We initiated administration of thalidomide (100 mg daily) and dexamethasone (20 mg for 4 days per month). After 8 months of treatment, she achieved complete hematological remission, defined as the disappearance of monoclonal protein and a normalized free light chain ratio, which led to improvement of her renal insufficiency. She has shown sustained hematological and organ response for 31 months with thalidomide therapy. Thus, thalidomide therapy seems to be a promising approach to the treatment of LCDD.     

Development of rapid light-chain deposition disease in hepatic arteries with severe ischemic cholangitis in a multiple myeloma patient treated with melphalan, prednisone and lenalidomide

Light-chain deposition disease (LCDD) is a multisystemic disorder associated with plasma cell dyscrasias and multiple myeloma. It is histologically characterized by the deposition of a homogeneous, in electron microscopy granular, slightly eosinophilic material showing positivity usually for kappa light chains. In contrast to AL-amyloidosis, the material is negative for Congo red. LCDD mainly involves the kidneys as the predominant organ manifestation resulting in a nephrotic syndrome. However, involvement of other tissues such as liver and heart have been described. Here we report a case of severe ischemic cholangitis in a patient with multiple myeloma receiving chemotherapy with melphalan, prednisone, and lenalidomide. Histopathological analysis revealed LCDD of the hepatic arteries as the underlying cause. This is to our knowledge the first case of LCDD of terminal liver arteries as a cause of intrahepatic ischemic cholangitis.     

Light-heavy chain deposition disease progressing to multiple myeloma

Light chain deposition disease (LCDD) and light and heavy chain deposition disease (LHCDD) are rare clinical entities that have been associated with multiple myeloma, with monoclonal gammopathy of unknown significance (MGUS), or without any detectable protein abnormality. Renal failure is common, the diagnosis is difficult and prolonged survival is rare. The first patient with LHCDD and MGUS who progressed to multiple myeloma after 11 years is presented. A rising level of monoclonal IgA immunoglobulin, bone marrow plasmacytosis, and the presence of multiple bone marrow lesions on magnetic resonance imaging provided the first evidence of disease evolution. When management of serious complications permits a long survival, some patients with LCDD or LHCDD will develop multiple myeloma.     

Synthesis of abnormal immunoglobulins in lymphoplasmacytic disorders with visceral light chain deposition

Three patients presented with renal or more diffuse tissue deposits of a nonamyloid material reactive with anti-κ antibody by immunofluorescence. All patients had progressive renal failure with the nephrotic syndrome and extensive tubular basement membrane deposits. Glomerular lesions were conspicuous but heterogeneous. One patient also had hepatic deposits with peliosis at histopathologic examination. An underlying lymphoplasmacytic disorder was found in all patients: multiple myeloma in one, pleomorphic lymphoplasmacytic malignancy analogous to Waldenström's macroglobulinemia in one and bone marrow monoclonal plasmacytosis without overt myeloma in one. Biosynthesis experiments in two cases showed production of abnormal κ chains which were not detected in appreciable amounts in serum and urine. These light chains had an aberrant size (abnormally short or large), their apparent molecular weight was larger in secretion than in cytoplasmic extracts (suggesting their glycosylation) and they were secreted as polymers. These results suggest a causal relationship between production of abnormal light chains and tissue deposition.     

The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias

Immunocytic dyscrasias may be manifested by MIDD often presenting with renal manifestations. The diagnosis is established when deposits are shown by immunopathologic methods to contain a single light-chain isotype in patients who have a monoclonal Ig in the serum or urine, altered kappa:lambda ratio in bone marrow, and/or abnormal biosynthesis of Igs in bone marrow cell cultures. The morphologic expressions of deposits are varied: fibrillar in AL, granular and punctate in LCDD, granular or crystalline in LHCDD, and crystalline in type I cryoglobulinemia.