Viswanathan Seethalakshmi, Bayly Angela, Brown David A, Neill Levina, Piza Michael, Nankivell Brian
Tissue Pathology and Diagnostic Oncology, NSW Health Pathology-ICPMR, Westmead Hospital, NSW, Australia; University of Sydney, NSW, Australia; University of Western Sydney, NSW, Australia.
Tissue Pathology and Diagnostic Oncology, NSW Health Pathology-ICPMR, Westmead Hospital, NSW, Australia.
Pathology. 2025 Jul 4. doi: 10.1016/j.pathol.2025.06.001.
Monoclonal immunoglobulin (MIg)-associated renal diseases are caused by nephrotoxic MIg originating from underlying plasma cell or lymphoid clone. The present study is an analysis of patient demographics, pathological characteristics, haematological and renal biomarkers of 83 biopsy-proven cases of diseases mediated by MIg, accrued from 6196 renal biopsies in a single Australian tertiary referral centre, over a decade. Older patients were more commonly affected with 89.2% of patients over the age of 50 years, with a male predominance. The spectrum consisted of direct MIg deposition diseases with organised and non-organised deposits, immunoglobulin light-chain amyloidosis +/- light chain cast nephropathy (AL amyloidosis +/- LCCN; 60.2%), cryoglobulinaemic glomerulonephritis types I and II (6%), monoclonal immunoglobulin deposition disease +/- light-chain cast nephropathy (MIDD +/- LCCN; 14.4%), proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease (PGNMID; 13.3%), light-chain proximal tubulopathy (LCPT; 1.2%), light-chain cast nephropathy (LCCN; 2.4%), and indirect complement-mediated lesions including monoclonal thrombotic microangiopathy (TMA; 1.2%) and C3 glomerulopathy (1.2%). PGNMID was the only type of lesion seen with post-transplant graft recurrences (3.6%). Tissue clonality was reliably established by immunofluorescence (IF) on frozen tissue, with paraffin IF and immunohistochemistry as useful salvage procedures. An underlying plasma cell clone was identified in 80.3% cases and a lymphoid clone in 19.7% cases. An overt haematological malignancy was seen in 39.8% of cases. A confirmed diagnosis of monoclonal gammopathy of renal significance (MGRS) was made in 70.5% of cases and renal biopsy preceded haematological investigations in 65.8% of cases, emphasising the significant role of the pathologist in the accurate diagnosis and classification of these lesions. MIg-mediated renal diseases can be accurately diagnosed and classified on renal biopsies. The presence of LCCN was associated with adverse renal outcome and overall survival. Future studies with a larger sample size are necessary to determine individual parameters that affect renal and overall survival.
单克隆免疫球蛋白（MIg）相关肾疾病由源自潜在浆细胞或淋巴克隆的肾毒性MIg引起。本研究分析了在澳大利亚一家三级转诊中心十年间6196例肾活检中确诊的83例由MIg介导的疾病患者的人口统计学特征、病理特征、血液学和肾脏生物标志物。老年患者更常受累，50岁以上患者占89.2%，男性居多。疾病谱包括有组织和无组织沉积的直接MIg沉积病、免疫球蛋白轻链淀粉样变性±轻链管型肾病（AL淀粉样变性±LCCN；60.2%）、I型和II型冷球蛋白血症性肾小球肾炎（6%）、单克隆免疫球蛋白沉积病±轻链管型肾病（MIDD±LCCN；14.4%）、伴有单克隆免疫球蛋白沉积病的增殖性肾小球肾炎（PGNMID；13.3%）、轻链近端肾小管病（LCPT；1.2%）、轻链管型肾病（LCCN；2.4%）以及间接补体介导的病变，包括单克隆血栓性微血管病（TMA；1.2%）和C3肾小球病（1.2%）。PGNMID是移植后移植物复发时唯一出现的病变类型（3.6%）。通过对冷冻组织进行免疫荧光（IF）可可靠地确定组织克隆性，石蜡IF和免疫组化可作为有用的补救方法。80.3%的病例中鉴定出潜在浆细胞克隆，19.7%的病例中鉴定出淋巴克隆。39.8%的病例中可见明显的血液系统恶性肿瘤。70.5%的病例确诊为具有肾意义的单克隆丙种球蛋白病（MGRS），65.8%的病例在血液学检查之前进行了肾活检，强调了病理学家在这些病变的准确诊断和分类中的重要作用。MIg介导的肾疾病可通过肾活检准确诊断和分类。LCCN的存在与不良肾脏结局和总生存期相关。需要进行更大样本量的未来研究以确定影响肾脏和总生存期的个体参数。
