Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, P.R. China.
Ren Fail. 2024 Dec;46(1):2359024. doi: 10.1080/0886022X.2024.2359024. Epub 2024 Jun 4.
The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.
110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.
In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.
FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.
M 型磷脂酶 A2 受体（PLA2R）相关的原发性膜性肾病（PMN）是一种成人免疫相关性疾病，发病率不断增加，治疗反应也各不相同，其中炎症可能导致其多因素免疫发病机制。纤维蛋白原-白蛋白比值（FAR）作为一种新的炎症生物标志物，与 PMN 之间的关系尚不清楚。因此，本研究旨在阐明 FAR 与 PMN 疾病活动和治疗反应之间的关系。
2017 年 1 月至 2021 年 12 月，南京医科大学第一附属医院共纳入 110 例经活检证实的 PLA2R 相关 PMN 肾病综合征患者。采用 Cox 回归和受试者工作特征（ROC）曲线分析探讨非缓解（NR）的独立危险因素和 FAR 的预测能力。根据最佳截断值，研究患者被分为低 FAR 组（≤截断值）和高 FAR 组（>截断值）。采用 Spearman 相关分析评估 FAR 与基线临床病理特征之间的关系。Kaplan-Meier 法评估 FAR 对缓解的影响。
在整个研究队列中，78 例（70.9%）患者达到完全或部分缓解（CR 或 PR）。预测缓解结局（CR+PR）的 FAR 最佳截断值为 0.233。Kaplan-Meier 生存分析表明，高 FAR 组（>0.233）比低 FAR 组（≤0.233）获得 CR 或 PR 的概率显著降低（Log Rank 检验，=0.021）。较高的 FAR 水平被确定为 NR 的独立危险因素，与低 FAR 组相比，高 FAR 组发生 NR 的可能性高 2.27 倍（HR 2.27，95%CI 1.01，5.13，=0.048）。在接受钙调神经磷酸酶抑制剂（CNIs）治疗的患者中，这些关系仍然稳健。在多变量 Cox 回归模型中，高 FAR 组 NR 的发生率是低 FAR 组的 4.00 倍（HR 4.00，95%CI 1.41，11.31，=0.009）。此外，ROC 分析显示 FAR 对 CR 或 PR 的预测价值为 0.738（曲线下面积 AUC），抗 PLA2R Ab 的 AUC 为 0.675。当结合 FAR 和抗 PLA2R Ab 时，AUC 提高至 0.766。
FAR 与 PMN 中的蛋白尿和抗 PLA2R Ab 显著相关。作为 NR 的独立危险因素，FAR 可能成为一种潜在的基于炎症的预后工具，用于识别治疗反应不良的病例，最佳预测结局的截断值为 0.233。
