Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features
Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features
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DOI：
10.1046/j.1523-1755.2003.00853.x
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发表时间：
2003-04-01
影响因子：
19.6
通讯作者：
D'Agati, VD
中科院分区：
文献类型：
--
作者：
Rosenstock, JL;Markowitz, GS;D'Agati, VD
背景目前关于肾小球肾炎（FGN）与免疫性类纤维化性肾小球肾炎（IT）的相关性仍存在争议。为了更好地确定其临床病理特征和结果，我们报告了1980年至2001年67例活检病例的最大单中心系列，其中包括61例FGN和6例IT。FGN的定义是肾小球免疫沉积的刚果红阴性随机取向的纤维< 30 nm（平均20.1 ± 0.4 nm）。IT的定义是肾小球沉积的中空、堆叠的微管≥ 30 nm（平均值为38.2 ± 5.7 nm）。FGN占总自体肾活检的0.6%，IT是罕见的10倍（0.06%）。FGN中的沉积物以免疫球蛋白G（IgG）为主，96%为多克隆沉积。19例FGN中IgG亚型分析显示4例为单型沉积（2例IgG 1和2例IgG 4），15例为寡型沉积（均为IgG 1和IgG 4结合）。在IT中，83%的沉积物以IgG为主，67%的沉积物为单克隆（3个IgG 1 κ和1个IgG 1 λ）。FGN患者的平均年龄为57岁，92%为白人，39%为男性。活检时，FGN患者具有以下临床特征（平均值，范围）：肌酐3.1 mg/dL（0.5 - 14），蛋白尿6.5 g/天（0.8 - 25），60%显微血尿和59%高血压。FGN的组织学类型多种多样，包括弥漫性增生性肾小球肾炎（DPGN）（9例）、膜性增生性肾小球肾炎（MPGN）（27例）、系膜增生性/硬化性肾小球肾炎（MES）（13例）、膜性肾小球肾炎（MGN）（4例）和弥漫性硬化性肾小球肾炎（DS）（8例）。与MES和MGN相比，更具增殖性（MPGN和DPGN）和硬化性（DS）形式表现出更高的肌酐和更高的蛋白尿。FGN至终末期肾病（ESRD）的中位时间为24.4个月，至ESRD的平均时间因组织学亚型而异：DS 7个月，DPGN 20个月，MPGN 44个月，MES 80个月，MGN 87个月。免疫抑制治疗（给予36%的FGN患者）无统计学显著性影响。通过考克斯回归（风险比，置信区间，P值），进展为ESRD的独立预测因子是活检时的肌酐[2.05（1.55 - 2.72）P < 0.001]和间质纤维化的严重程度[2.01（1.05 - 3.85）P = 0.034]。尽管IT与FGN的临床表现、组织学类型和预后相似，但与单克隆丙种球蛋白病（P = 0.014）、潜在淋巴组织增生性疾病（P = 0.020）和低补体血症（P = 0.032）的相关性更大。FGN是一种特发性疾病，其特征在于具有限制性γ同种型的多克隆免疫沉积物。大多数患者存在显著的肾功能不全，尽管进行了免疫抑制治疗，但结局仍较差，且结局与组织学亚型相关。相比之下，IT通常含有单克隆IgG沉积物，并与潜在的异常蛋白血症和低补体血症显著相关。从免疫病理学、超微结构和临床上看，FGN与更罕见的IT的鉴别是合理的。
Background. Controversy surrounds the relatedness of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulonephritis (IT).Methods. To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of Congo red-negative randomly oriented fibrils of < 30 nm (mean, 20.1 +/- 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of ≥ 30 nm (mean, 38.2 +/- 5.7 nm).Results. FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were immunoglobulin G (IgG) dominant and polyclonal in 96%. IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two IgG1 and two IgG4) and oligotypic deposits in 15 (all combined IgG1 and IgG4). In IT, deposits were IgG dominant in 83% and monoclonal in 67% (three IgG1κ and one IgG1λ). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range): creatinine 3.1 mg/dL (0.5 to 14), proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59% hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative glomerulonephritis (DPGN) (nine cases), membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13), membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher creatinine and greater proteinuria compared to MES and MGN. Median time to end-stage renal disease (ESRD) was 24.4 months for FGN and mean time to ESRD varied by histologic subtype: DS 7 months, DPGN 20 months, MPGN 44 months, compared to MES 80 months and MGN 87 months. There was no statistically significant effect of immunosuppressive therapy (given to 36% of FGN patients). By Cox regression (hazard ratio, confidence interval, P value), independent predictors of progression to ESRD were creatinine at biopsy [2.05 (1.55 to 2.72) P < 0.001] and severity of interstitial fibrosis [2.01 (1.05 to 3.85) P = 0.034]. Although IT had similar presentation, histologic patterns, and outcome compared to FGN, it had a greater association with monoclonal gammopathy (P = 0.014), underlying lymphoproliferative disease (P = 0.020), and hypocomplementemia (P = 0.032).Conclusion. FGN is an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant renal insufficiency and have a poor outcome despite immunosuppressive therapy, and outcome correlates with histologic subtype. By contrast, IT often contains monoclonal IgG deposits and has a significant association with underlying dysproteinemia and hypocomplementemia. Differentiation of FGN from the much more rare entity IT appears justified on immunopathologic, ultrastructural, and clinical grounds.