克隆导向治疗成功治疗增殖性肾小球肾炎伴单克隆免疫球蛋白沉积伴严重急性肾损伤：病例报告

摘要(中文译文)

伴单克隆免疫球蛋白沉积的增生性肾小球肾炎（PGNMID）是单克隆丙种球蛋白病伴肾脏意义（MGRS）的一种形式，其特征为单克隆免疫球蛋白沉积于肾小球所致的肾损伤。虽然仅在20%~30%的PGNMID患者中可检测到克隆，但针对浆细胞或B细胞的治疗被建议有效。近期病例报告提示，免疫失调（如病毒感染或疫苗接种）可能触发PGNMID的发生或复发。本文报告一例无可检测克隆的PGNMID患者，在病毒性肠炎后复发，表现为严重急性肾损伤（AKI）和肾病综合征。患者为60岁男性，最初诊断为IgG3 λ型PGNMID伴肾病综合征（尿蛋白/肌酐比值（UPCR）为5.3 g/gCr），接受非克隆导向治疗方案，包括糖皮质激素。患者初始获得部分缓解，UPCR为1~3 g/gCr，镜下血尿阴性。约2年后，患者在患病毒性肠炎后出现需要透析的严重AKI（肌酐11.0 mg/dL）及肾病综合征（UPCR 5.5 g/gCr，血清白蛋白2.4 g/dL）。第二次肾活检证实与PGNMID一致的相似损伤模式，伴IgG3 λ沉积、严重毛细血管内炎症、系膜扩张及肾小球毛细血管腔显著狭窄。由于对糖皮质激素冲击治疗无效，遂启动达雷妥尤单抗和硼替佐米克隆导向治疗。该干预使患者停止透析，尿液指标改善。临床医生应认识到，PGNMID病程中可能出现严重AKI，可能由感染触发。此外，本病例强调了达雷妥尤单抗和硼替佐米克隆导向治疗在治疗无可检测克隆的复发性PGNMID中的疗效。

Abstract

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of monoclonal gammopathy of renal significance, characterized by kidney injury caused by monoclonal immunoglobulin deposition in the glomeruli. While detectable clones are only found in 20-30% of PGNMID, plasma cell- or B-cell-targeting therapies are suggested to be effective. Recent case reports suggested immune dysregulation, such as viral infections or vaccinations, could potentially trigger the onset or relapse of PGNMID. Here, we report a case of PGNMID without detectable clones, which relapsed after viral enteritis, presenting with severe acute kidney injury (AKI) and nephrotic syndrome. A 60-year-old man, originally diagnosed with IgG3 lambda type PGNMID with nephrotic syndrome (urine protein/creatinine ratio (UPCR) of 5.3 g/gCr), was treated with non-clone-directed therapeutic regimens, including glucocorticoids. The patient initially achieved a partial response with a UPCR of 1-3 g/gCr and negative microhematuria. Approximately 2 years later, the patient presented with severe AKI (Cr 11.0 mg/dL) requiring dialysis, and nephrotic syndrome (UPCR 5.5 g/gCr, and serum albumin 2.4 g/dL) after having had viral enteritis. Second kidney biopsy confirmed a similar pattern of injury consistent with PGNMID with IgG3 lambda deposition, severe endocapillary inflammation, mesangial expansion, and remarkable narrowing of the glomerular capillary lumina. As it was refractory to glucocorticoid pulse therapy, clone-directed therapies with daratumumab and bortezomib were initiated. This intervention resulted in the cessation of dialysis and an improvement in urinary parameters. Clinicians should recognize that severe AKI may develop during the course of PGNMID, potentially triggered by infections. Furthermore, this case highlights the efficacy of clone-directed therapy with daratumumab and bortezomib in treating recurrent PGNMID without detectable clones.

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