Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa, Japan.
Department of Internal Medicine, Nagaoka Red Cross Hospital, Nagaoka, Japan.
Clin Exp Nephrol. 2011 Oct;15(5):615-626. doi: 10.1007/s10157-011-0521-2. Epub 2011 Sep 7.
IgG4-related disease has attracted wide attention recently. It is characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive plasma cells into multiple organs, with the kidney being one representative target. Although several sets of diagnostic criteria for autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4-related tubulointerstitial nephritis (TIN) without AIP from other types of TIN. To clarify the entity of IgG4-related kidney disease (IgG4-RKD) and support in-depth studies, the Japanese Society of Nephrology has established a working group to prepare diagnostic criteria for IgG4-RKD.
The working group analyzed 41 patients with IgG4-RKD, and collected the following data to devise a diagnostic algorithm and diagnostic criteria for IgG4-RKD: clinical features including extra-renal organ involvement, urinalysis and serological features including serum IgG4 levels, imaging findings demonstrated by computed tomography (CT), renal histology with IgG4 immunostaining, and response to steroid therapy.
The conditions for criteria are as follows. (1) Presence of some kidney damage, as manifested by abnormal urinalysis or urine marker(s) and/or decreased kidney function with either elevated serum IgG level, hypocomplementemia, or elevated serum IgE level. (2) Kidney imaging studies showing abnormal renal imaging findings, i.e., multiple low density lesions on enhanced CT, diffuse kidney enlargement, hypovascular solitary mass in the kidney, and hypertrophic lesion of the renal pelvic wall without irregularity of the renal pelvic surface. (3) Serum IgG4 level exceeding 135 mg/dl. (4) Renal histology showing two abnormal findings: (a) dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/high power field (HPF) and/or ratio of IgG4-positive plasma cells/IgG positive plasma cells >40%. (b) Characteristic 'storiform' fibrosis surrounding nests of lymphocytes and/or plasma cells. (5) Extra-renal histology showing dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/HPF and/or ratio of IgG4-positive plasma cells/IgG-positive plasma cells >40%. The diagnosis is classified into 3 stages of definite, probable and possible according to the combinations of the above conditions. Thirty-nine cases (95.1%) were diagnosed with IgG4-RKD according to the criteria.
The provisional criteria and algorithm appear to be useful for clarifying the entity of IgG4-RKD and seeking underlying IgG4-RKD cases; however, further experience is needed to confirm the validity of these criteria.
IgG4 相关疾病最近受到广泛关注。其特征为血清 IgG4 水平升高，大量 IgG4 阳性浆细胞浸润多个器官，肾脏是代表性靶器官之一。虽然目前已有数套自身免疫性胰腺炎（AIP）的诊断标准，且肾脏病变被认为是 AIP 的胰腺外表现，但不伴有 AIP 的 IgG4 相关肾小管间质性肾炎（TIN）与其他类型 TIN 难以区分。为明确 IgG4 相关肾脏疾病（IgG4-RKD）的实体，并为深入研究提供支持，日本肾脏病学会成立了一个工作组，制定 IgG4-RKD 的诊断标准。
该工作组分析了 41 例 IgG4-RKD 患者，收集了以下数据以制定 IgG4-RKD 的诊断算法和诊断标准：包括肾脏外器官受累在内的临床特征、尿液分析和包括血清 IgG4 水平在内的血清学特征、计算机断层扫描（CT）显示的影像学表现、IgG4 免疫染色的肾脏组织学表现，以及对类固醇治疗的反应。
标准条件如下。（1）存在某种肾脏损伤，表现为尿液分析异常或尿液标志物异常和/或肾功能下降，伴有血清 IgG 水平升高、低补体血症或血清 IgE 水平升高。（2）肾脏影像学检查显示异常肾脏影像学表现，即增强 CT 上多个低密度病变、弥漫性肾脏增大、肾脏内低血供单发肿块和肾盂壁肥厚而肾盂表面无不规则。（3）血清 IgG4 水平超过 135mg/dl。（4）肾脏组织学显示两个异常发现：（a）致密的淋巴浆细胞浸润，浸润的 IgG4 阳性浆细胞>10/高倍视野（HPF）和/或 IgG4 阳性浆细胞/IgG 阳性浆细胞的比例>40%。（b）特征性“席纹状”纤维化围绕淋巴细胞和/或浆细胞巢。（5）肾脏外组织学显示致密的淋巴浆细胞浸润，浸润的 IgG4 阳性浆细胞>10/HPF 和/或 IgG4 阳性浆细胞/IgG 阳性浆细胞的比例>40%。根据上述条件的组合，将诊断分为明确、可能和可能 3 个阶段。根据标准，39 例（95.1%）诊断为 IgG4-RKD。
暂定标准和算法似乎有助于明确 IgG4-RKD 的实体，并寻找潜在的 IgG4-RKD 病例；然而，需要进一步的经验来确认这些标准的有效性。
