目的:结晶球蛋白血症是一种罕见的以单克隆免疫球蛋白(Migs)血管内结晶为特征的综合征。有关肾脏受累的数据仅限于病例报告。该系列描述了晶体球蛋白诱导的肾病(CIN)的临床病理特征。
方法:案例系列。
方法:从梅奥诊所和哥伦比亚大学的肾脏病理学档案中发现了19例N患者。CIN由光学(LM)和电子显微镜(EM)可见的血管内(细胞外)MIg晶体定义。
结果:在病例中,68%为男性,65%为高加索人(中位年龄56岁)。大多数患者出现严重AKI(中位数肌酐3.5mg/dL),血尿,和轻度蛋白尿(中位数1.1g)。常见的肾外表现是宪法(67%),皮肤(56%),和风湿病(50%)。50%的病例患有低补体血症。血液系统疾病为肾意义的单克隆丙种球蛋白病(MGRS)(72%),淋巴瘤(17%),或骨髓瘤(11%),这些疾病中有65%与CIN同时发现。所有患者在SPEP/SIF上都有MIg(IgGκ占65%)。sFLC比率在40%的肾脏范围之外,骨髓活检检测到67%的相关克隆。在LM上,晶体涉及肾小球(100%)和血管(47%),常伴有炎症反应(89%)和纤维蛋白(58%)。通过EM,所有病例均表现出晶体亚结构(主要是次晶)。石蜡包埋组织上的免疫荧光(IF)比冷冻组织更敏感(92%对47%),以证明晶体组成(IgGκ为63%)。16例患者获得了随访(中位数为20个月)。百分之八十一接受了类固醇治疗,44%血浆置换,38%血液透析,69%的化疗。接受克隆指导治疗的患者中,有90%的患者实现了肾脏恢复。20%的人没有(p=0.017)。
结论:回顾性设计,小样本量。
结论:CIN是与淋巴浆细胞病(主要是MGRS)相关的肾病的罕见原因,通常表现为严重的AKI和肾外表现。诊断通常需要在石蜡包埋的肾组织上进行IF。迅速开始克隆导向治疗,再加上皮质类固醇和血浆置换,可能导致肾功能的恢复。
OBJECTIVE: Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to
case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN).
METHODS: Case series.
METHODS: Nineteen CIN cases were identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light (LM) and electron microscopy (EM).
RESULTS: Among the cases, 68% were male and 65% were Caucasian (median age 56 years). Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow
biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017).
CONCLUSIONS: Retrospective design, small sample size.
CONCLUSIONS: CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires IF performed on paraffin embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.