膜增生性肾小球肾炎伴单克隆免疫球蛋白沉积的临床特征观察

doi:10.11958/20260051

摘要/Abstract

摘要：

目的分析膜增生性肾小球肾炎伴单克隆免疫球蛋白沉积（PGNMID）的临床及病理特征、治疗方法与转归。方法回顾性分析我院经肾穿刺活检确诊的3例PGNMID患者的临床资料、病理资料、治疗方案及预后特点，探讨发病机制并评价不同治疗方法的疗效。结果 3例PGNMID患者均为女性，平均年龄（68.00±12.29）岁，均表现为肾小球源性血尿、大量蛋白尿及不同程度肾功能损伤。肾活检病理光镜下均以膜增生性肾炎为特征，免疫荧光可见IgG亚型免疫球蛋白及轻链沉积于毛细血管襻与系膜区，均伴补体C3沉积，电镜下均可见足突弥漫性融合（>95%），电子致密物沉积于内皮下及系膜区，其中2例基底膜内亦可见电子致密物沉积。3例患者均采用肾素-血管紧张素转化酶抑制剂联合针对致病B细胞或浆细胞克隆实施靶向治疗，1个月后24 h尿蛋白定量均有不同程度下降。2例患者在治疗2~3个月时达到部分缓解，在第6~7个月达完全缓解，1例患者经治疗后随访至6个月仍为部分缓解。结论 PGNMID患者常表现为肾病综合征并伴有肾功能减退，病理上常以IgG3沉积的膜增生性肾小球肾炎为特征，早期诊治可获得较好临床治疗效果。

关键词: 肾小球肾炎, 膜增生性, 抗体, 单克隆, 免疫球蛋白G, 病理学, 利妥昔单抗, 增生性肾小球肾炎伴单克隆免疫球蛋白沉积, 靶向治疗

Abstract:

Objective To analyze the clinical and pathological characteristics, treatment modalities and prognosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID), and to offer references for the diagnosis and treatment of this disease. Methods A retrospective analysis was conducted on the clinical data, pathological manifestations, treatment regimens and prognostic characteristics of three patients with PGNMID diagnosed by renal biopsy in our hospital. The aim was to explore the pathogenesis and evaluate the efficacy of different treatment methods. Results All 3 PGNMID patients were female, with an average age of (68.00 ± 12.29) years. Throughout the disease course, all patients exhibited glomerular hematuria, massive proteinuria and varying degrees of renal function impairment. Histopathological examination under light microscopy indicated membranoproliferative glomerulonephritis. Immunofluorescence demonstrated the deposition of IgG subtype immunoglobulins and light chains in the capillary loops and mesangial regions, accompanied by complement C3 deposition. Electron microscopy revealed diffuse fusion of podocytes (>95%) and electron-dense material deposition in the subendothelial and mesangial regions. In 2 cases, electron-dense material deposition was also observed in the basement membrane. All three patients received a combination of renin-angiotensin-converting enzyme inhibitors (RASi) and clonal targeted therapy. One month later, their 24-hour urinary protein levels showed varying degrees of reduction. Two patients achieved partial response (PR) after 2-3 months of treatment, achieved complete response (CR) in the 6th to 7th month. One patient maintained PR during the follow-up period up to the month 6. Conclusion Patients with PGNMID usually present with nephrotic syndrome accompanied by renal function decline. Pathologically, it is often characterized by membranoproliferative glomerulonephritis with IgG3 deposition. Early diagnosis and treatment can lead to better clinical therapeutic outcomes.

Key words: glomerulonephritis, membranoproliferative, antibodies, monoclonal, immunoglobulin G, pathology, rituximab, proliferative glomerulonephritis with monoclonal immunoglobulin deposition, targeted therapy

中图分类号:

R692.31

图/表 7

参考文献 27

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病例		年龄/岁		基本病情				血尿/HPF	24 h UTP/ （g/d）			ALB/ （g/L）		SCr/ （μmol/L）		eGFR/ [mL/（min·1.73m²）]
1		54		颜面部水肿1年，加重1个月				满视野	5.07			35.00		85.00		70.17
2		73		发现Scr升高3个月，双下肢水肿2个月				57.00	6.30			26.80		108.00		46.78
3		77		确诊膜增生性肾炎15年，蛋白尿加重3个月				10.20	11.24			27.20		262.00		15.75
病例	Hb/ （g/L）		血κ轻链/（g/L）		血λ轻链/（g/L）	κ/λ	抗核抗体谱			免疫固定电泳	血清IgG/（g/L）		补体C3/（g/L）		补体C4/（g/L）		骨髓活检浆细胞数/个
1	99		5.44		2.58	2.11	抗SSA/Ro（+++）、抗Ro-52抗体（+++）			阴性	23.80		0.60		0.09		1
2	108		1.87		0.68	2.75	抗SSA/Ro（+++）、抗Ro-52抗体（+++）			阴性	7.70		0.93		0.30		2
3	108		1.35		1.03	1.31	抗SSA/Ro（+++）、抗Ro-52抗体（++）			阴性	6.83		0.94		0.34		1

病例		年龄/岁		基本病情				血尿/HPF	24 h UTP/ （g/d）			ALB/ （g/L）		SCr/ （μmol/L）		eGFR/ [mL/（min·1.73m²）]
1		54		颜面部水肿1年，加重1个月				满视野	5.07			35.00		85.00		70.17
2		73		发现Scr升高3个月，双下肢水肿2个月				57.00	6.30			26.80		108.00		46.78
3		77		确诊膜增生性肾炎15年，蛋白尿加重3个月				10.20	11.24			27.20		262.00		15.75
病例	Hb/ （g/L）		血κ轻链/（g/L）		血λ轻链/（g/L）	κ/λ	抗核抗体谱			免疫固定电泳	血清IgG/（g/L）		补体C3/（g/L）		补体C4/（g/L）		骨髓活检浆细胞数/个
1	99		5.44		2.58	2.11	抗SSA/Ro（+++）、抗Ro-52抗体（+++）			阴性	23.80		0.60		0.09		1
2	108		1.87		0.68	2.75	抗SSA/Ro（+++）、抗Ro-52抗体（+++）			阴性	7.70		0.93		0.30		2
3	108		1.35		1.03	1.31	抗SSA/Ro（+++）、抗Ro-52抗体（++）			阴性	6.83		0.94		0.34		1

病例	免疫荧光		超微结构电子致密物位	光镜
病例	优势蛋白类型及位置	补体类型	超微结构电子致密物位	肾小球病变类型	嗜复红物质沉积位置
1	IgG2-Lambda；团块状/毛细血管襻、系膜区	C3（+）、C4（+/-）、C1q（阴性）	系膜区、内皮下	膜增生性肾炎	系膜区、内皮下沉积
2	IgG3-Kappa；团块状、颗粒状/毛细血管襻、系膜区	C3（+++）、C4（阴性）、C1q（阴性）	系膜区、内皮下，基底膜内偶见	膜增生性肾炎	系膜区、内皮下沉积
3	IgG3-Kappa；花瓣状/毛细血管襻、系膜区	C3（+++）、C4（阴性）、C1q（+/-）	系膜区、内皮下，个别基底膜内	膜增生性肾炎	系膜区、内皮下沉积

病例	免疫荧光		超微结构电子致密物位	光镜
病例	优势蛋白类型及位置	补体类型	超微结构电子致密物位	肾小球病变类型	嗜复红物质沉积位置
1	IgG2-Lambda；团块状/毛细血管襻、系膜区	C3（+）、C4（+/-）、C1q（阴性）	系膜区、内皮下	膜增生性肾炎	系膜区、内皮下沉积
2	IgG3-Kappa；团块状、颗粒状/毛细血管襻、系膜区	C3（+++）、C4（阴性）、C1q（阴性）	系膜区、内皮下，基底膜内偶见	膜增生性肾炎	系膜区、内皮下沉积
3	IgG3-Kappa；花瓣状/毛细血管襻、系膜区	C3（+++）、C4（阴性）、C1q（+/-）	系膜区、内皮下，个别基底膜内	膜增生性肾炎	系膜区、内皮下沉积

病例	治疗方案	不良反应	开始缓解时间	部分缓解时间	完全缓解时间	随访时间	目前情况
1	厄贝沙坦300 mg、达格列净10 mg每日1次口服+利妥昔单抗（第0、2周，6个月分别静脉滴注1 g）+甲泼尼龙片晨起20 mg口服，规律减量，6个月后停药+环磷酰胺每月0.8 g静脉滴注，维持1年	中性粒细胞、淋巴细胞轻度下降	第1个月	第3个月	第6个月	12个月	24 h UTP下降至0.2 g/d以内，SCr及镜下血尿恢复正常；厄贝沙坦+达格列净口服维持治疗
2	沙库巴曲缬沙坦100 mg每日2次口服+硼替佐米1.3 mg/m²第1、8、15、22天静脉滴注+环磷酰胺300 mg/m² 第1、8、15天静脉滴注+地塞米松40 mg第1~2、8~9、15~16、22~23天口服	无	第1个月	第2个月	第7个月	10个月	24 h UTP维持在0.15 g/d左右，SCr及镜下血尿恢复正常，沙库巴曲缬沙坦口服维持治疗
3	利妥昔单抗第0、2周分别静脉滴注1 g+环磷酰胺第0、2周分别静脉滴注0.4 g，此后每月单用环磷酰胺0.6 g静脉滴注，目前仍在维持治疗中	无	第1个月	第6个月	无	6个月	24 h UTP下降至1 g/d左右，SCr维持在200 μmol/L左右，厄贝沙坦口服维持治疗