Supplementary Material for: The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits.

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis.

Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023.

Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dl and 4.3 gm/gm respectively. A detectable monoclonal (M) protein was detected in 28% of cases, however, only 3 patients had underlying hematologic disorders (Multiple Myeloma, CLL, and B cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/Kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to ESKD, with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone directed therapy.

Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials.

引言：伴单克隆免疫球蛋白（Immunoglobulin, Ig）沉积的增生性肾小球肾炎（PGNMID）是一类罕见肾脏疾病，其特征为单克隆蛋白检出率偏低且肾脏预后不良。目前缺乏有效治疗手段，部分原因在于相关研究数据有限、对其发病机制的认知不足。

方法：本研究依托克利夫兰诊所肾脏活检流行病学项目，对2015年1月至2023年3月期间收治的18例PGNMID患者开展回顾性分析。

结果：PGNMID患者以男性（占比67%）及白人（占比78%）居多，中位年龄为60岁。超过三分之二的患者表现为高血压、肾功能不全及血尿，另有26%的患者符合肾病综合征诊断标准。活检时患者的平均血清肌酐水平为3.2 mg/dl，平均尿蛋白水平为4.3 gm/gm。仅28%的病例可检出单克隆（M）蛋白，其中仅3例患者合并基础血液系统疾病，分别为多发性骨髓瘤（Multiple Myeloma）、慢性淋巴细胞白血病（Chronic Lymphocytic Leukemia, CLL）及B细胞淋巴瘤。肾脏病理检查以毛细血管内增生性病变/膜增生性病变模式（占比72%）、IgGκ型（占比83%）及IgG3亚型（占比56%）为主要表现。8例患者（占比44%）进展为终末期肾病（End-Stage Kidney Disease, ESKD），中位进展时间为首次肾脏活检后7.5个月。另有6例患者主要经克隆靶向治疗实现了完全缓解。

结论：尽管肾脏活检可见单克隆免疫球蛋白沉积，但本队列中仅28%的PGNMID患者可检出循环单克隆蛋白。与其他副蛋白血症性肾脏疾病不同，PGNMID患者的肾脏预后不良，本队列中有44%的患者在肾脏活检后进展为终末期肾病（中位时间7.5个月）。尽管多数患者无法检出克隆性病变，但克隆靶向治疗仍是改善预后的主要治疗手段。因此，仍需进一步深入研究PGNMID的发病机制，以指导未来的治疗探索与临床试验开展。