Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India.
Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, 605006, India.
BMC Nephrol. 2024 Oct 25;25(1):378. doi: 10.1186/s12882-024-03772-y.
Podocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression.
We conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis.
Serum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737-0.960), sensitivity of 81%, and specificity of 71%.
This study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis.
足细胞病包括微小病变性肾病（MCD）、局灶节段性肾小球硬化症（FSGS）和塌陷性肾小球病（CG），是导致肾小球足细胞损伤的肾脏疾病，导致大量蛋白尿和肾病综合征（NS）。炎症在慢性肾脏病（CKD）的进展中起着关键作用，最近的研究将炎症生物标志物与肾功能下降联系起来。肿瘤坏死因子-α（TNF-α）是一种重要的炎症细胞因子，与它的循环受体 TNFR1 和 TNFR2 相互作用。TNF-α 途径已被牵连到 FSGS 和 MCD 的发病机制中。循环中升高的 TNFR2 水平与足细胞病中肾功能恶化相关，这表明 TNF-α 炎症途径对疾病进展有显著贡献。
我们进行了一项研究，纳入了 53 名经活检证实的 MCD 或 FSGS 患者和 53 名年龄和性别匹配的健康对照者。所有患者均随访 18 个月。我们在基线和 3 个月时分析了血清和尿液中的 TNFR2 水平和基因表达。为了评估 TNFR2 对持续性估计肾小球滤过率（eGFR<30mL/min/1.73m）下降、缓解和复发的预测能力，我们采用 Cox 回归分析。此外，我们还使用 ROC 曲线分析评估了其对预测进展为 4 期 CKD 的预后价值。
与对照组相比，患者的血清和尿液中的 TNFR2 水平明显升高。在单因素 Cox 回归分析中，血清 TNFR2 是持续性 eGFR 下降（HR 1.017，95%CI：1.003 至 1.032，p=0.018）、缓解（HR 0.995，95%CI：0.992 至 0.999，p=0.006）和复发（HR 1.005，95%CI：1.001 至 1.010，p=0.029）的显著预测因子。ROC 曲线分析表明，血清 TNFR2 水平对预测进展为 4 期 CKD 具有很强的预后能力，AUC 为 0.848（95%CI：0.737-0.960），灵敏度为 81%，特异性为 71%。
本研究强调了循环 TNFR2 在原发性足细胞病患者肾损伤中的关键作用。升高的 TNFR2 水平是持续性 eGFR 下降和疾病复发的重要预测因子，突出了其作为疾病进展和预后标志物的潜力。
