Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Pathology, Medical University of Vienna, Vienna, Austria.
J Nephrol. 2021 Jun;34(3):839-849. doi: 10.1007/s40620-020-00914-x. Epub 2020 Dec 11.
Glomerulonephritis (GN), including post-transplant IgAN (post-Tx IgAN) is an important contributor to decreased long-term allograft survival. The immunopathological detection of the complement degradation product C4d in glomeruli (C4dG) has been recently described as a risk factor in native kidney IgAN, however little is known about C4dG deposition in post-Tx IgAN. We hypothesized that glomerular C4d may indicate a more aggressive disease course and worse allograft survival in patients with post-Tx IgAN.
In this retrospective study we assessed the presence and clinical relevance of C4dG in patients with post-transplant IgAN. We analyzed 885 renal allograft recipients, including 84 patients with post-transplant GN. All patients were transplanted between January 1999 and April 2006 and underwent at least one biopsy for differnt causes. The primary endpoint was death-censored graft survival, with a median follow-up of 9.6 (IQR 3.8-13.2) years.
The prevalence of post-Tx GN was 9.5%. Twenty-seven patients with post-Tx IgAN were included. C4dG positive patients (N = 18, 66.7%) had significantly worse allograft survival compared to C4dG negative post-Tx IgAN patients and patients without post-Tx IgAN [C4dG positive: 27.8% vs. 55.6% and 66.0%; log-rank: p = 0.01]. C4dG remained a significant risk factor (HR 2.22, 95% CI 1.27-3.87) for allograft loss even after adjustment for T cell mediated rejection (TCMR) and antibody mediated rejection.
Glomerular C4d deposition is an independent risk factor for worse graft-survival in patients with post-Tx IgAN, even after adjusting for other risk factors such as antibody mediated rejection. Assessment of glomerular C4d deposition may provide a valuable prognostic risk assessment tool to identify high risk patients in post-Tx IgAN.
肾小球肾炎（GN），包括移植后 IgA 肾病（post-Tx IgAN），是导致长期移植物存活率降低的重要因素。最近有研究表明，肾小球中补体降解产物 C4d（C4dG）的免疫病理学检测是原发性肾脏 IgA 肾病的一个危险因素，但对于 post-Tx IgAN 中 C4dG 沉积的了解甚少。我们假设，在 post-Tx IgAN 患者中，肾小球 C4d 可能预示着更具侵袭性的疾病进程和更差的移植物存活率。
在这项回顾性研究中，我们评估了 post-transplant IgAN 患者中 C4dG 的存在及其临床相关性。我们分析了 885 例肾移植受者，其中包括 84 例 post-transplant GN 患者。所有患者均于 1999 年 1 月至 2006 年 4 月期间接受移植，并因不同原因至少接受过一次活检。主要终点是死亡相关移植物存活率，中位随访时间为 9.6（IQR 3.8-13.2）年。
post-Tx GN 的患病率为 9.5%。纳入了 27 例 post-Tx IgAN 患者。C4dG 阳性患者（N=18，66.7%）的移植物存活率明显差于 C4dG 阴性 post-Tx IgAN 患者和无 post-Tx IgAN 的患者[C4dG 阳性：27.8%比 55.6%和 66.0%；log-rank：p=0.01]。即使在调整 T 细胞介导的排斥反应（TCMR）和抗体介导的排斥反应后，C4dG 仍然是移植物丢失的显著危险因素（HR 2.22，95%CI 1.27-3.87）。
即使在调整抗体介导的排斥反应等其他危险因素后，肾小球 C4d 沉积仍是 post-Tx IgAN 患者移植物存活率较差的独立危险因素。评估肾小球 C4d 沉积可能为 post-Tx IgAN 患者提供有价值的预后风险评估工具，以识别高危患者。
