Johny Joseph, John Elenjickal Elias, Roy Sanjeet, Alam Rizwan, Mani Selvin Sundar Raj, Jose Nisha, Lalwani Manish, Eapen Jeethu Joseph, Yusuf Sabina, Thomas Athul, David Vinoi George, Varughese Santosh, Alexander Suceena
Departments of Nephrology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India.
Pathology and Histopathology, Christian Medical College Vellore, Ranipet Campus, Ranipet, India.
Indian J Nephrol. 2024 Jul 22;35(3):355-367. doi: 10.25259/ijn_489_23.
Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare entity classified under the umbrella of monoclonal gammopathy of renal significance. The clinical implications of circulating monoclonal immunoglobulin (MIg), light chain restriction on immunofluorescence (IF) microscopy, histopathological pattern, and type of therapy on renal outcomes are not clearly defined.
Sixteen patients of PGNMID diagnosed between 2013 and 2020 were included from a biopsy registry of 11,459 patients at a single center. Follow-up data was collected from electronic medical records until June 2021.
The mean age of the cohort was 41.7 ± 13.5 years. Forty-four (7/16) percent showed monoclonal protein on serum or urine electrophoresis, 25% (3/12) had IgG kappa by serum immunofixation electrophoresis (IFE) and 38% (5/13) had abnormal kappa: lambda free light chain (FLC) ratio. The predominant light microscopy pattern, membranoproliferative glomerulonephritis (MPGN) was seen in 7/16 (43.7%) patients. The predominant heavy chain detected by IF microscopy was IgG (13/16, 81.3%). Kappa and lambda light chain restriction were seen in 56.3 (9/16) and 43.8 (7/16) percent of patients respectively. Circulating monoclonal kappa light chains were detected in 50 and 29% of kappa-PGNMID patients by IFE and FLC assay respectively. None of the lambda-PGNMID patients had detectable circulating monoclonal lambda light chains. Patients with circulating MIg had more proteinuria, lower estimated glomerular filtration rate, and a higher percentage of plasma cells on bone marrow biopsy. Thirty-eight percent of our cohort (5/13) progressed to kidney failure over a median (range) period of 3 (IQR, 1-7) months. Of these, 4/5 received immunosuppression, and 1/5 were treated with plasma cell-targeted chemotherapy.
PGNMID is a rare disease with a biopsy incidence of 0.1%. Only a quarter of patients with PGNMID have circulating MIg. Presence of circulating MIg, type of monoclonal light chain restriction in kidney biopsy, and type of therapy did not predict renal outcomes. Patients with MPGN pattern had favorable renal outcomes despite a higher degree of proteinuria at presentation.
伴单克隆免疫球蛋白沉积的增殖性肾小球肾炎（PGNMID）是一种罕见疾病，归类于具有肾脏意义的单克隆丙种球蛋白病范畴。循环单克隆免疫球蛋白（MIg）、免疫荧光（IF）显微镜下轻链限制、组织病理学模式以及治疗类型对肾脏结局的临床影响尚不清楚。
从一个单中心11459例患者的活检登记中纳入了2013年至2020年间诊断的16例PGNMID患者。从电子病历中收集随访数据至2021年6月。
该队列的平均年龄为41.7±13.5岁。44%（7/16）的患者在血清或尿电泳中显示单克隆蛋白，25%（3/12）的患者血清免疫固定电泳（IFE）显示IgG κ，38%（5/13）的患者κ：λ游离轻链（FLC）比值异常。主要的光镜模式，即膜增生性肾小球肾炎（MPGN）在7/16（43.7%）的患者中可见。IF显微镜检测到的主要重链为IgG（13/16，81.3%）。κ和λ轻链限制分别在56.3%（9/16）和43.8%（7/16）的患者中可见。通过IFE和FLC检测，分别在50%和29%的κ-PGNMID患者中检测到循环单克隆κ轻链。没有λ-PGNMID患者检测到循环单克隆λ轻链。有循环MIg的患者蛋白尿更多、估计肾小球滤过率更低，且骨髓活检时浆细胞百分比更高。我们队列中的38%（5/13）患者在中位（范围）3（IQR，1 - 7）个月内进展为肾衰竭。其中，4/5接受了免疫抑制治疗，1/5接受了浆细胞靶向化疗。
PGNMID是一种罕见疾病，活检发病率为0.1%。只有四分之一的PGNMID患者有循环MIg。循环MIg的存在、肾活检中单克隆轻链限制的类型以及治疗类型并不能预测肾脏结局。尽管MPGN模式的患者在就诊时蛋白尿程度较高，但肾脏结局良好。
