Objective

Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement.

Method

This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 μmol/L), all with biopsy-proven nephropathy.

Results

All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 μmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients.

Conclusion

Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.

中文翻译：

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与严重肾脏受累的 ANCA 相关性血管炎患者相比，双阳性（ANCA 和抗 GBM 抗体）患者的肾脏和总体结果：一项具有系统肾脏病理学分析的多中心回顾性研究

客观的

双阳性患者 (DPP) 结合了肾小球基底膜 (GBM) 疾病和抗中性粒细胞胞浆抗体 (ANCA) 的血清和/或组织学发现，这种情况很少见，而且描述很少。本研究旨在比较 DPPs 和严重肾脏受累的 ANCA 相关性血管炎 (AAV) 患者的特征。

方法

这项回顾性多中心研究比较了 33 名 DPP 和 45 名 AAV 患者的严重肾脏受累（血清肌酐 > 300 μmol/L），这些患者均患有经活检证实的肾病。

结果

所有 DPP（包括 18% 的血清抗 GBM 抗体呈阴性）呈现严重的急性肾功能衰竭并伴有组织学 GBM 受累。与 AAV 患者相比，他们的血清肌酐更高（719 vs 501 μmol/L；p = 0.006），需要初始肾脏替代治疗的患者比例更高（82% vs 36%；p < 0.001）。Berden 分类差异显着 (p = 0.003)，新月体肾小球肾炎较多，DPPs 硬化性病变较少。DPP 患者的一年肾脏存活率明显低于 AAV 患者（27% vs 64%；p < 0.0002）。具有相当比例的 ANCA 亚型（三分之二具有抗髓过氧化物酶自身抗体）、肾外表现的数量（三分之二主要是肺部）、诱导缓解的免疫抑制剂和组间的中位随访（3 年），

结论

尽管 DPPs 具有两种血管炎的特征，但抗 GBM 成分是主要表型，与严重肾功能衰竭的 AAV 患者相比，其肾脏表现和预后更为严重。建议所有快速进展的肾小球肾炎患者同时检测抗体和系统地进行肾活检，以识别这种难以治疗的罕见疾病。