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目的探讨肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在抗中性粒细胞胞浆抗体相关性血管炎(ANCAassociated vasculitis,AAV)中对肾脏损害程度及预后意义。方法回顾性分析我院2013年7月至2017年7月肾内科经病理活检确诊的41例AAV肾损害患者的临床资料。采用放射免疫法检测血清TNF-α水平。随访肾脏结局利用ROC曲线取TNF-α截点(Cut off值)为14.1 pg/ml,将总体AAV肾损害患者分为高水平TNF-α(≥14.1 pg/ml)及低水平TNF-α(<14.1 pg/ml)组,并比较2组患者生物学特征、肾脏病理特征及预后。结果高水平TNF-α组与低水平组相比,伯明翰血管炎活动性评分(Birmingham vasculitis activity score,BVAS)及肌酐(serum creatinine,Scr)、IL-6、IL-8水平显著升高(P<0.05),肾小球滤过率(estimated glomerular filtration rate,e GFR)、补体3(complement 3,C3)显著下降(P<0.05)。TNF-α与ALB、eGFR、Cys-c、BVAS、ESR、IL-6具有相关性,相关系数r分别为-0.37、-0.49、0.55、0.50、0.32、0.34(P<0.05)。肾脏病理特征显示TNF-α水平升高组肾间质纤维化及肾小管萎缩程度更重(P<0.05)。Kaplan-Meier生存分析显示TNF-α水平升高组肾脏存活率低(Log-Rank=5.230,P=0.022)。结论血清TNF-α水平升高是反映肾脏损伤程度及预后的危险因素。
Objective To investigate the extent of renal damage and prognostic significance of tumor necrosis factor-α (TNF-α) in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods The clinical data of 41 AAV patients with renal damage confirmed by pathological biopsy in our department from July 2013 to July 2017 were retrospectively analyzed. Serum TNF-α levels were measured by radioimmunoassay. Follow-up Renal Outcomes The patients with total AAV nephropathy were divided into high-level TNF-α (≥14.1 pg / ml) and low-level TNF-α by using ROC curve with cutoff value of 14.1 pg / <14.1 pg / ml) group. The biological characteristics, renal pathological features and prognosis of the two groups were compared. Results The levels of Birmingham vasculitis activity score (BVAS) and serum creatinine (Scr), IL-6 and IL-8 in patients with high level TNF-α were significantly higher than those in patients with low level <0.05), glomerular filtration rate (eGFR) and complement 3 (C3) decreased significantly (P <0.05). The correlation coefficient of TNF-α and ALB, eGFR, Cys-c, BVAS, ESR and IL-6 were -0.37, -0.49,0.55,0.50,0.32,0.34 respectively (P <0.05). The pathological features of kidney showed that renal interstitial fibrosis and renal tubular atrophy were more serious (P <0.05). Kaplan-Meier survival analysis showed that the renal survival rate was lower in patients with elevated TNF-α levels (Log-Rank = 5.230, P = 0.022). Conclusion The increase of serum TNF-α is a risk factor reflecting the degree of renal damage and prognosis.