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)。     

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.     

遗传性纤维蛋白原A-α链淀粉样变性

目的：系统性淀粉样变性以AL型和AA型常见，近年国外报道遗传性淀粉样变性发生率并不低，常被误诊为AL型。本文通过报道国内首例遗传性纤维蛋白原A-α链淀粉样变性的临床病理特点，加深对遗传性淀粉样变性的认识，提高其诊断率。方法：观察患者的临床病理特点，肾组织进行A蛋白、κ、λ轻链、纤维蛋白原、甲状腺激素结合蛋白、载脂蛋白AI染色，并进行纤维蛋白原A-α链DNA序列分析。结果：本例患者系青年女性，以蛋白尿和高血压起病，肾功能正常，伴肾脏病家族史。组织学改变显示淀粉样物质只沉积于肾小球，而小管间质及血管不受累。肾小球纤维蛋白原A．仅链染色阳性，A蛋白、κ、λ轻链、甲状腺激素结合蛋白和载脂蛋白AI染色阴性。基因测序提示存在纤维蛋白原A-α链的基因突变。结论：遗传性纤维蛋白原A-α链淀粉样变性以蛋白尿和高血压起病，淀粉样变性只累及肾小球，小管间质及血管一般很少受累，纤维蛋白原染色是诊断该病的关键，而纤维蛋白原A-α链基因测序则有助于进一步明确诊断。     

肾淀粉样变性

肾淀粉样变性陈惠萍曾彩虹关键词肾淀粉样变性肾病综合征蛋白尿中图法分类号Ｒ５９７．２１病例报告患者男性，５３岁，因腹泻、浮肿、蛋白尿近４个月于１９９７－０６－２３入院。１９９７年３月中旬无诱因腹泻１～２次／ｄ，大便呈糊状，无浓血，腹泻前无腹痛，无里急后...     

遗传性纤维蛋白原Aα链肾脏淀粉样变性1例报道并文献复习

正遗传性淀粉样变性是一种常染色体显性遗传疾病,由Ostertag于1932年首次报道~[1],发病机制与编码各种淀粉样变性前体蛋白的基因突变有关,在肾脏遗传性淀粉样变性中遗传性纤维蛋白原Aα链淀粉样变(hereditary fibrinogen Aα-chain amyloidosis,AFib)最为常见。本文首次报道了1例纤维蛋白原Aα链(fibrinogen Aα,FGA)新位点杂合突变-     

膜性肾病合并系统性淀粉样变性

老年男性患者,临床表现为肾病综合征,肾活检证实为肾小球膜性肾病、肾间质淀粉样变性;皮肤脂肪组织淀粉样变性.最终诊断膜性肾病合并系统性淀粉样变性.     

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...     

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。     

肾脏重链沉积病（IgG-γ1型重链）1例

讨论1例肾脏重链沉积病（IgG-γ1重链）。57岁男性,临床表现高血压、肾病综合征、大量蛋白尿、肾功能不全,病情进行性发展,血肌酐升至4381,tmol／L时,双肾超声体积仍不小。肾外损害不明显。肾活检光镜下肾小球呈“结节样病变”,刚果红染色阴性。免疫荧光见免疫球蛋白G（IgG）和IgG亚型IgG_1（γ1重链单抗）沿肾小球毛细血管袢及肾小管基膜（TBM）线样沉积,IgA和IgM阴性。IgG_2,IgG_3,IgG_4阴性。K轻链和九轻链染色阴性。电镜下见肾小球基膜内侧及TBM外侧电子致密物沉积。通过临床．实验室．病理结合,光学显微镜．免疫病理．电子显微镜结合,特别是针对性免疫病理检查,确诊为肾脏重链沉积病（IgG-γ1重链）。     

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues.

A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens.

In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log₁₀%amyloid). The results of sex-, age-, and Log₁₀%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group.

There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.     

经皮肾穿刺活检诊断淀粉样变性患者超声心动图特点及其预后分析

目的 通过分析经皮肾穿刺活检明确诊断为淀粉样变性肾病伴心脏受累患者的临床及超声心动图特点,为心肌淀粉样变性患者的早期诊断提供帮助。方法 共纳入经皮肾穿刺活检确诊的淀粉样变性肾病患者45例,收集患者行肾穿刺活检时的临床资料(年龄、性别、血压等)、超声心动图指标(室间隔厚度、左心室舒张期末内径、左心室射血分数等),对比心脏受累与未受累者指标差异及预后。结果 超声心动图指标分析显示,心脏受累组较未受累组室间隔厚度、左心室后壁厚度增加,差异具有统计学意义(P＜0.05)。心脏受累组中位生存期15月,较心脏未受累组明显下降,差异具有统计学意义(P＜0.05)。结论 经皮肾穿刺活检诊断淀粉样变性患者超声心动图提示室间隔厚度及左心室后壁厚度增加,且室间隔厚度≥10 mm,可作为判断是否合并心肌淀粉样变性的早期依据。     

The amino acid sequence of a glycosylated AL-chain from a patient with primary amyloidosis

An amyloid fibril protein (Owe) related to primary amyloidosis was found to be a glycosylated complete immunoglobulin light chain (AL). The amino acid sequence revealed a protein composed of 214 residues and with a glycosylation site in position 20. The sequence established an AL V-region corresponding to a κ 1b germline gene, but differs from that in 12 positions. Eight of them are in the FR-regions, positions 7, 13, 20, 42, 46, 60, 76 and 79. The J-segment is that of JκII.     

Bilateral localized amyloidosis of the ureters: clinicopathology and therapeutic approaches in two cases

Localized amyloidosis in the ureter is a rare condition, in which immunoglobulin light chain is locally synthesized, causing thickening of ureteric walls by deposits of immunoglobulin-related amyloid. Since the clinical features of ureteral amyloidosis with ureteric stricture and/or hydroureteronephrosis closely resemble those of malignancy involving the ureters, nephroureterctomy is usually performed for this disease. We describe two aged patients with localized amyloidosis on the bilateral ureters. In both cases, left hydronephrosis with left ureteral stricture was found. They were treated with total nephroureterctomy and Aλ amyloid deposition was confirmed in the resected ureters. Several months later right ureteral stenosis was found. One patient was treated with percutaneous nephrostomy to preserve his renal function and the other with corticosteroids. This appeared to result in significant regression of the stenotic lesion. In both cases, all examinations for systemic involvement of organs were negative. Corticosteroids may be of use in treating immunoglobulin-derived localized amyloidosis in the ureters.     

Primary amyloidosis (AL) in families

We report the occurrence of immunoglobulin-related amyloidosis (AL) in three separate families, each family having two members affected. None of the six patients had evidence to suggest the presence of familial amyloidosis (AF). Previously, immunoglobulin-related amyloidosis (AL) was considered to be a sporadic disease process. Because of the occasional familial occurrence of other monoclonal gammopathies such as monoclonal gammopathy of undetermined significance, multiple myeloma, and macroglobulinemia of Waldenstr?m, amyloidosis (AL) should be added to the list of immunopathies with a familial predisposition.     

Immunoglobulin heavy light chain test quantifies clonal disease in patients with AL amyloidosis and normal serum free light chain ratio

Abstract

Background: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are used for clonal detection in plasma cell dyscrasias, while serum free light chain (sFLC) testing provides quantitation of clonal disease. Up to 20% of patients with light chain (AL) amyloidosis may present with normal FLC ratio (FLCr).

Methods: We assessed the diagnostic, quantitative and prognostic potential of serum heavy light chain ratio (HLCr) in 199 untreated patients at initial evaluation.

Results: An abnormal HLCr was found in 37.2%, abnormal FLCr in 81.9% and positivity by SIFE/UIFE in 94% of patients. HLCr together with SIFE/UIFE identified clonality in 94% patients; the combination with FLCr yielded 100% sensitivity. An HLCr abnormality was significantly over-represented in normal compared to abnormal FLCr group (63.9% versus 31.3%). HLCr did not predict overall survival (OS) (log rank, p?=?0.09), while an abnormal FLCr was associated with decreased OS (log rank, p?=?0.03). The combined use of both ratios trended toward increased OS in the abnormal HLCr/normal FLCr group (log rank, p?=?0.11; Wilcoxon, p?=?0.04). On multivariate analysis, HLCr was not predictive of OS, whereas an abnormal FLCr was associated with shorter OS (HR?=?1.7, p?=?0.04).

Conclusions: The HLC assay has potential as a supplemental test to quantify monoclonal protein in patients with normal FLCr results.     

肝淀粉样变性1例报告

<正>1病例资料女性患者,39岁,贵州籍。因"右上腹疼痛伴厌油、尿黄3个月"于2012年11月29日入院。患者于3个月前出现右上腹胀痛,放射至右肩背部,时轻时重,伴厌油、恶心、尿黄,无皮肤、巩膜黄染、皮肤瘙痒及陶土色大便,无畏寒、发热、呕吐、腹泻、呕血、黑便。多次于当地医院诊治,上述症状无好转而转诊本院。本院门诊行上腹部增强CT提示肝硬化、肝右叶前方软组织影,胆管肿瘤可疑。肝功能提示:ALT 114.5 U/L、AST