尿骨桥蛋白对成年狼疮肾炎患者诱导治疗反应和肾脏预后的预测研究

    Urinary osteopontin predicted response to induction therapy and long-term renal outcomes in adults with lupus nephritis

    • 摘要:
      目的  探讨尿骨桥蛋白(urinary osteopontin,uOPN)对成年狼疮肾炎(lupus nephritis,LN)患者诱导治疗反应和肾脏预后的预测作用。
      方法  纳入2017年9月至2020年12月期间西北大学附属医院•西安市第三医院收治的53例Ⅲ/Ⅳ型LN患者作为研究对象,同时选取24名同期来我院体检的年龄与性别相匹配的健康志愿者作为健康对照组。采用酶联免疫吸附试验法测定uOPN水平,在基线和诱导治疗后进行肾活检。根据美国风湿病学会标准,将患者分为临床反应组和临床无反应组。肾脏活动性指数评分改善≥50%的患者纳入组织学反应组,其他患者纳入组织学无反应组。
      结果  LN患者基线和治疗后uOPN水平均显著高于健康对照组2.33(1.84,2.83)mg/L、2.07(1.55,2.72)mg/L比0.94(0.70,1.46)mg/L,P<0.05,且Ⅳ型LN患者基线uOPN水平显著高于Ⅲ型LN患者2.39(1.93,3.07)mg/L比1.87(1.57,2.45)mg/L,P=0.005。与临床反应组和组织学反应组相比,临床无反应组和组织学无反应组患者基线uOPN3.06(1.92,3.41)mg/L比2.46(2.24,3.10)mg/L,3.12(2.03,3.35)mg/L比2.47(2.15,3.13)mg/L、治疗后uOPN3.04(1.56,3.63)mg/L比2.37(1.82,2.65)mg/L,3.09(1.76,3.57)mg/L比2.30(1.79,2.68)mg/L水平均更高(P<0.05)。此外,只有临床反应组和组织学反应组治疗后uOPN2.37(1.82,2.65)mg/L比2.46(2.24,3.10)mg/L,2.30(1.79,2.68)mg/L比2.47(2.15,3.13)mg/L水平较基线值降低(P<0.05),而无反应组治疗前后uOPN水平变化不明显(P>0.05)。经多因素Logistic回归分析,基线uOPN是LN诱导治疗组织学反应的独立预测因子(P<0.05)。经受试者工作特征曲线分析,基线uOPN水平预测LN患者诱导治疗组织学反应的曲线下面积为0.721(95%CI:0.550~0.892),特异度为55.6%,敏感度为81.8%。
      结论  uOPN反映了Ⅲ/Ⅳ型LN患者的肾脏活动,可预测LN患者诱导治疗的组织学反应。治疗后高uOPN水平可能反映了肾损伤进展和较差的肾脏预后。

       

      Abstract:
      Objective  To explore the role of urinary osteopontin (uOPN) in predicting clinical responses to induction therapy and renal prognosis in adults with lupus nephritis (LN).
      Methods  A total of 53 type Ⅲ/Ⅳ LN adults were recruited. At the same time, 24 healthy volunteers visiting our hospital for physical examination in the same period were selected as healthy control group. Levels of uOPN were determined by enzyme-linked immunosorbent assay (ELISA). Renal biopsies were performed at baseline and after induction therapy. According to the criteria of American College of Rheumatology (ACR), they were divided into two groups of clinical response or non-response. Patients with ≥50% improvement in renal activity index scores were selected as histological response group.
      Results  Baseline and post-treatment levels of uOPN were significantly higher in LN patients than those in healthy controls 2.33(1.84, 2.83)mg/L, 2.07(1.55, 2.72)mg/L vs 0.94(0.70, 1.46)mg/L(P<0.05). And baseline uOPN in type Ⅳ LN patients were significantly higher than those with type Ⅲ LN 2.39(1.93, 3.07)mg/L vs 1.87(1.57, 2.45)mg/L, P=0.005. As compared with clinical/histological response subgroup, baseline uOPN 3.06(1.92, 3.41)mg/L vs 2.46(2.24, 3.10)mg/L , 3.12(2.03, 3.35)mg/L vs 2.47(2.15, 3.13)mg/L and OPN level post-treatment 3.04(1.56, 3.63)mg/L vs 2.37(1.82, 2.65)mg/L, 3.09(1.76, 3.57)mg/L vs 2.30(1.79, 2.68)mg/L were higher in non-response subgroup (P<0.05). Furthermore, only clinical/histological response subgroup demonstrated a lower level of OPN 2.37 (1.82, 2.65)mg/L vs 2.46 (2.24, 3.10)mg/L, 2.30(1.79, 2.68)mg/L vs 2.47 (2.15, 3.13)mg/L from baseline post-treatment (P<0.05) while non-response group showed no significant change before and after treatment (P>0.05). Multivariate Logistic regression analysis revealed that baseline uOPN was an independent predictor of histological response to LN induction therapy (P<0.05). ROC curve analysis indicated that the area under the curve (AUC) of baseline uOPN level in predicting histological response to induction therapy was 0.721(95%CI:0.550-0.892) with a specificity of 55.6% and a sensitivity of 81.8% in LN patients.
      Conclusions  Reflecting renal activity in adults with type Ⅲ/Ⅳ LN, uOPN may predict histological responses to induction therapy. Elevated level of uOPN post-treatment may reflect the progression of renal injury and worse renal prognosis.

       

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