Terashita Maho, Selamet Umut, Midha Shonali, Nadeem Omar, Laubach Jacob, Rennke Helmut G, Murakami Naoka
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Kidney Int Rep. 2023 Sep 22;8(12):2765-2777. doi: 10.1016/j.ekir.2023.09.022. eCollection 2023 Dec.
Monoclonal gammopathy of renal significance (MGRS) is characterized by monoclonal immunoglobulin deposition in kidneys. However, monoclonal immunoglobulin and responsible clone(s) are not always detectable. Treatment response and kidney outcome of MGRS without detectable clones remain unclear.
In this single-center, retrospective cohort study, we identified MGRS without detectable clones from our biopsy repository between 2010 and 2022. We investigated the correlations between treatment regimens and kidney outcomes defined by proteinuria and estimated glomerular filtration rate (eGFR), and the impact of repeat kidney biopsy.
Our study cohort included 29 cases (27 native kidney and 2 transplant allograft biopsies) of MGRS without detectable clones. At diagnosis, median serum creatinine was 1.8 mg/dl (interquartile range [IQR] 1.3-2.7), with proteinuria 4.6 g/gCr (IQR 2.3-7.9). Treatment regimens were variable: 6 (21%) received conservative therapy, 13 (45%) received plasma cell clone-directed therapy, 8 (28%) received lymphocytic clone-directed therapy, and 2 (7%) received nonclone-directed immunosuppressive therapy. Of 24 patients with proteinuria >0.5 g/gCr at diagnosis, 9 (38%) and 6 (25%) achieved complete response (CR) and partial response (PR), respectively. If interstitial fibrosis and tubular atrophy (IFTA) was >50% at the initial biopsy, less proportion of patients achieved CR. Six of 7 repeat biopsies showed progression of chronic changes (e.g., IFTA) but provided limited information on treatment response.
Treatment regimens and outcomes of MGRS without detectable clones were extremely variable. Repeat biopsy provided limited information to assess disease activity or the need for additional treatment. More sensitive tools are needed to detect clones and to assess treatment response.
具有肾脏意义的单克隆丙种球蛋白病（MGRS）的特征是单克隆免疫球蛋白在肾脏中沉积。然而，单克隆免疫球蛋白和相关克隆并不总是能够检测到。未检测到克隆的MGRS的治疗反应和肾脏结局仍不清楚。
在这项单中心回顾性队列研究中，我们从2010年至2022年的活检资料库中识别出未检测到克隆的MGRS。我们研究了治疗方案与由蛋白尿和估计肾小球滤过率（eGFR）定义的肾脏结局之间的相关性，以及重复肾脏活检的影响。
我们的研究队列包括29例未检测到克隆的MGRS病例（27例为自体肾活检，2例为移植肾活检）。诊断时，血清肌酐中位数为1.8mg/dl（四分位间距[IQR]为1.3 - 2.7），蛋白尿为4.6g/gCr（IQR为2.3 - 7.9）。治疗方案各不相同：6例（21%）接受保守治疗，13例（45%）接受针对浆细胞克隆的治疗，8例（28%）接受针对淋巴细胞克隆的治疗，2例（7%）接受非克隆定向免疫抑制治疗。在诊断时蛋白尿>0.5g/gCr的24例患者中，分别有9例（38%）和6例（25%）达到完全缓解（CR）和部分缓解（PR）。如果初始活检时间质纤维化和肾小管萎缩（IFTA）>50%，达到CR的患者比例较低。7次重复活检中有6次显示慢性病变（如IFTA）进展，但提供的治疗反应信息有限。
未检测到克隆的MGRS的治疗方案和结局差异极大。重复活检为评估疾病活动或额外治疗需求提供的信息有限。需要更敏感的工具来检测克隆并评估治疗反应。
