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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2022, Vol. 11 ›› Issue (05) : 249 -257. doi: 10.3877/cma.j.issn.2095-3216.2022.05.002

论著

特发性膜性肾病患者血清β2微球蛋白与局灶节段性肾小球硬化病变的关系分析
王晓玉1, 胡豪飞2, 韦宁荣3, 毕慧欣4,†()   
  1. 1. 541001　桂林医学院研究生院；546300　河池市人民医院肾内科
    2. 518037　深圳市第二人民医院肾内科
    3. 546300　河池市人民医院肾内科
    4. 541001　桂林医学院研究生院；541001　桂林医学院附属医院肾内科
  • 收稿日期:2021-12-24 出版日期:2022-10-28
  • 通信作者: 毕慧欣
  • 基金资助:
    国家自然科学基金(81960679); 广西自然科学基金(2016GXNSFBA380057); 广西高校中青年教师基础能力提升项目(2020KY2022)

Relationship between serum β2 microglobulin and the lesion of focal segmental glomerulosclerosis in patients with idiopathic membranous nephropathy

Xiaoyu Wang1, Haofei Hu2, Ningrong Wei3, Huixin Bi4,†()   

  1. 1. Graduate School of Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region; Department of Nephrology, Hechi People′s Hospital, Hechi 546300, Guangxi Zhuang Autonomous Region
    2. Department of Nephrology, Shenzhen Second People′s Hospital, Shenzhen 518037, Guangdong Province
    3. Department of Nephrology, Hechi People′s Hospital, Hechi 546300, Guangxi Zhuang Autonomous Region
    4. Graduate School of Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region; Department of Nephrology, Affiliated Hospital of Guilin Medical College, Guilin 541001, Guangxi Zhuang Autonomous Region; China
  • Received:2021-12-24 Published:2022-10-28
  • Corresponding author: Huixin Bi
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引用本文：

王晓玉, 胡豪飞, 韦宁荣, 毕慧欣. 特发性膜性肾病患者血清β2微球蛋白与局灶节段性肾小球硬化病变的关系分析[J]. 中华肾病研究电子杂志, 2022, 11(05): 249-257.

Xiaoyu Wang, Haofei Hu, Ningrong Wei, Huixin Bi. Relationship between serum β2 microglobulin and the lesion of focal segmental glomerulosclerosis in patients with idiopathic membranous nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(05): 249-257.

目的

探讨特发性膜性肾病(IMN)患者的血清β2微球蛋白与其局灶节段性肾小球硬化(FSGS)病变的关系。

方法

本研究为单中心回顾性横断面研究，根据纳排标准纳入2013年6月至2021年9月在河池市人民医院住院经肾穿刺活检确诊为IMN的患者152例。根据有无合并FSGS病变将其分为无FSGS组及有FSGS组。比较两组患者人口学、生化及病理指标的差异。分析血清β2微球蛋白与肾间质病变积分、FSGS病变比例的相关性。采用多因素Logistic回归分析探讨血清β2微球蛋白与FSGS病变的关系。广义相加模型(GAM)用于探讨血清β2微球蛋白与FSGS病变的非线性关系。此外，对不同亚组间血清β2微球蛋白与FSGS病变的关系也进行了分析。

结果

在调整性别、年龄、民族、职业、病程、高血压病史、糖尿病、BMI、24 h尿蛋白、镜下血尿、血液血红蛋白、淋巴细胞、白蛋白、球蛋白、空腹血糖、尿酸、甘油三酯、高密度脂蛋白、肾间质萎缩纤维化等因素后，多因素Logistic回归分析显示血清β2微球蛋白是FSGS病变发生的独立危险因素(OR 1.421，95%CI：1.002~2.014，P＝0.049)。GAM分析发现血清β2微球蛋白与FSGS病变之间的关系为线性关系。亚组分析结果提示在有高血压病史的患者中血清β2微球蛋白与FSGS病变的关系增强(OR 4.086，95%CI：1.512~11.043)，而无高血压病史的患者未发现统计学关联(OR 1.007，95%CI：0.647~1.567, P＝0.975)。ROC曲线分析表明血清β2微球蛋白对于预测FSGS病变发生具有一定价值(AUC＝0.668)，最佳临界值为2.65 mg/L。与无高血压病史且血清β2微球蛋白<2.65 mg/L的IMN患者相比，有高血压病史且血清β2微球蛋白≥2.65 mg/L患者的FSGS病变发生风险增加3.7倍(OR 4.711，95%CI：1.732~12.812，P＝0.002)。

结论

血清β2微球蛋白升高与IMN患者的FSGS病变发生密切关联，在合并高血压病史的患者中血清β2微球蛋白对FSGS病变发生的影响增大。

关键词: 特发性膜性肾病, 局灶节段性肾小球硬化病变, 血清β2微球蛋白, 危险因素, 交互作用
Objective

To explore the relationship between serum β2 microglobulin and the lesion of focal segmental glomerulosclerosis (FSGS) in patients with idiopathic membranous nephropathy (IMN).

Methods

This study was a single-center retrospective cross-sectional research. According to the criteria for inclusion and exclusion, 152 patients, who were hospitalized at Hechi People′s Hospital and diagnosed with IMN by renal biopsy, were included. According to the presence or absence of FSGS lesion, the patients were divided into FSGS group and non-FSGS group. The differences in demographic, biochemical, and pathological indicators between the two groups were compared. The correlation between serum β2 microglobulin and renal interstitial lesion score or the proportion of FSGS lesion was analyzed. Multivariate logistic regression analysis was used to explore the relationship between serum β2 microglobulin and the FSGS lesion. The generalized additive model (GAM) was used to explore the nonlinear relationship between serum β2 microglobulin and the FSGS lesion. In addition, the relationship between serum β2 microglobulin and the FSGS lesion in different subgroups was also analyzed.

Results

After adjusting the factors including gender, age, ethnicity, occupation, course of disease, history of hypertension, diabetes, body mass index (BMI), 24 h urine protein, microscopic hematuria, blood hemoglobin, lymphocytes, albumin, globulin, fasting blood glucose, uric acid, triglycerides, high density lipoprotein, and renal interstitial atrophy and fibrosis, the multivariate logistic regression analysis showed that serum β2 microglobulin was an independent risk factor for the occurrence of FSGS lesion (OR 1.421, 95%CI: 1.002-2.014, P=0.049). GAM analysis found that the relationship between serum β2 microglobulin and the FSGS lesion was linear. The results of subgroup analysis suggested that the relationship between serum β2 microglobulin and the FSGS lesion was enhanced in patients with a history of hypertension (OR 4.086, 95%CI: 1.512-11.043), but not in patients without a history of hypertension (OR 1.007, 95%CI: 0.647-1.567) (P=0.975). ROC curve analysis showed that serum β2 microglobulin might be of value in diagnosing the occurrence of FSGS lesion (AUC=0.668), and the best cut-off value was 2.65 mg/L. It was found that compared with IMN patients without a history of hypertension and the serum β2 microglobulin <2.65 mg/L, the occurrence risk of FSGS lesion increased by 3.7 times (OR 4.711, 95%CI: 1.732-12.812, P=0.002) in patients with both a history of hypertension and the serum β2 microglobulin ≥2.65 mg/L.

Conclusion

The increase of serum β2 microglobulin was closely related to FSGS lesion occurrence in IMN patients. In patients with a history of hypertension the influence of serum β2 microglobulin on FSGS lesion occurrence was enhanced.

Key words: Idiopathic membranous nephropathy, Focal segmental glomerulosclerosis lesion, Serum β2 microglobulin, Risk factor, Interaction
图1 研究人群入选流程图
表1 患者的基线特征
指标 不伴FSGS组(n＝104) FSGS组(n＝48) 统计量 P值
性别[男(%)] 57(54.81) 38(79.17) 7.494 0.004
年龄(岁) 48.60±14.05 51.38±11.58 －1.349 0.234
民族[例(%)]     5.310 0.032
  汉 20(19.23) 5(10.42)    
  壮 65(62.50) 40(83.33)    
  其他 19(18.27) 3(6.25)    
农民[例(%)] 84(80.77) 39(81.25) 0.020 0.944
病程(月) 2.00(0.63，4.00) 3.50(1.00，7.50) －1.691 0.027
糖尿病[例(%)] 9(8.65) 5(10.42) 0.224 0.727
高血压病史[例(%)] 26(25.00) 21(43.75) 7.067 0.020
收缩压(mmHg) 137.86±21.89 147.17±21.74 －2.569 0.016
舒张压(mmHg) 85.07±12.38 89.10±15.28 －1.667 0.085
吸烟[例(%)] 19(18.27) 13(27.08) 1.292 0.215
饮酒[例(%)] 21(20.19) 8(16.67) 0.356 0.607
体重指数(kg/m2) 23.13±3.29 23.15±3.53 0.082 0.974
血尿[n(%)] 86(82.69) 42(87.50) 0.247 0.450
血红蛋白(g/L) 127.14±20.57 125.33±20.03 0.790 0.612
白蛋白(g/L) 25.25±5.54 24.79±6.19 0.502 0.641
估算的肾小球滤过率[ml/(min·1.73 m2)] 101.84±26.00 86.76±28.79 3.567 0.002
血尿酸(μmol/L) 397.52±109.99 410.65±127.02 －0.624 0.516
总胆固醇(mmol/L) 8.18±2.46 8.80±3.41 －1.274 0.207
甘油三酯(mmol/L) 1.80(1.31，2.87) 1.75(1.40，2.83) 0.358 0.914
高密度脂蛋白(mmol/L) 1.71±0.50 1.59±0.45 1.466 0.160
低密度脂蛋白(mmol/L) 5.43±2.04 5.93±2.89 －1.203 0.226
血清β2微球蛋白(mg/L) 2.70±1.21 3.55±1.68 －3.573 <0.001
空腹血糖(mmol/L) 5.45±1.41 5.46±1.71 0.364 0.947
血清抗磷脂酶A2受体抗体(RU/ml) 67.90(29.65，138.44) 53.84(9.14，268.00) －0.658 0.947
24 h尿蛋白定量(g) 4.19(2.76，6.37) 5.83(3.41，8.97) －3.158 0.004
球性硬化比例 0.00(0.00，10.74) 7.15(0.00，11.27) －1.403 0.038
肾间质病变积分(分) 2.00(1.00，2.00) 2.00(1.00，3.00) －2.907 0.010
膜性肾病分期[例(%)]       0.178
  Ⅰ 7(6.73) 0(0.00)    
  Ⅱ 76(73.08) 36(75.00)    
  Ⅲ+Ⅳ 21(20.19) 12(25.00)    
肾脏抗磷脂酶A2受体阳性[例(%)] 77(96.25) 35(89.74)   0.215
表2 单因素分析的结果
  指标 OR (95% CI) 统计量(Wald) P值
性别        
  女 57 (37.50%) 1.0    
  男 95 (62.50%) 3.133 (1.413~6.949) 7.899 0.005
年龄 49.47±13.343 1.016 (0.990~1.044) 1.420 0.233
民族        
  汉 25 (16.45%) 1.0    
  壮 105 (69.08%) 2.462 (0.856~7.078) 2.794 0.095
  其他 22 (14.47%) 0.632 (0.132~3.015) 0.332 0.564
职业        
  非农民 29 (19.08%) 1.0    
  农民 123 (80.92%) 1.032 (0.431~2.472) 0.005 0.944
病程(月) 5.493±11.387 1.031 (0.997~1.066) 3.257 0.071
糖尿病        
  否 138 (90.79%) 1.0    
  是 14 (9.211%) 1.227 (0.388~3.880) 0.122 0.727
高血压病史        
  否 105 (69.08%) 1.0    
  是 47 (30.92%) 2.333 (1.133~4.806) 5.281 0.022
体重指数(kg/m2) 23.14±3.36 1.002 (0.904~1.110) 0.001 0.974
收缩压(mmHg) 140.80±22.20 1.020 (1.003~1.036) 5.542 0.019
舒张压(mmHg) 86.34±13.44 1.023 (0.997~1.051) 2.914 0.088
血清抗磷脂酶A2受体抗体(RU/ml) 157.41±282.22 1.000 (0.999~1.002) 0.317 0.573
血红蛋白(g/L) 126.57±20.35 0.996 (0.979~1.013) 0.261 0.609
血尿        
  否 24 (15.79%) 1.0    
  是 128 (84.21%) 1.465 (0.542~3.962) 0.566 0.452
估算的肾小球滤过率[ml/(min·1.73 m2)] 97.08±27.73 0.979 (0.965~0.992) 9.257 0.002
白蛋白(g/L) 25.11±5.74 0.986 (0.928~1.047) 0.220 0.639
血尿酸(μmol/L) 401.66±115.37 1.001 (0.998~1.004) 0.427 0.514
总胆固醇(mmol/L) 8.38±2.80 1.081 (0.958~1.219) 1.584 0.208
甘油三酯(mmol/L) 2.66±2.62 0.987 (0.863~1.128) 0.039 0.844
高密度脂蛋白(mmol/L) 1.67±0.49 0.582 (0.273~1.241) 1.962 0.161
低密度脂蛋白(mmol/L) 5.59±2.35 1.093 (0.946~1.262) 1.461 0.227
血清β2微球蛋白(mg/L) 2.97±1.43 1.526 (1.178~1.978) 10.222 0.001
空腹血糖(mmol/L) 5.45±1.51 1.008 (0.803~1.265) 0.005 0.946
24 h尿蛋白定量(g) 5.54±3.65 1.161 (1.053~1.279) 9.074 0.003
球性硬化比例 0.08±0.13 5.047 (0.414~61.501) 1.610 0.204
肾间质积分(分) 1.80±1.13 1.582 (1.143~2.191) 7.634 0.006
肾脏抗磷脂酶A2受体        
  否 7 (5.88%) 1.0    
  是 112 (94.12%) 0.341 (0.072~1.605) 1.825 0.173
表3 不同模型血清β2微球蛋白与局灶节段性肾小球硬化的关系
变量 模型Ⅰ(OR，95%CI，P) 模型Ⅱ(OR，95%CI，P) 模型Ⅲ(OR，95%CI，P)
血清β2微球蛋白 1.526 (1.178~1.978) 0.001 1.479 (1.087~2.012) 0.003 1.421 (1.002~2.014) 0.049
血清β2微球蛋白三分位数      
  低 1.0 1.0 1.0
  中 1.152 (0.461~2.880) 0.761 1.190 (0.427~3.316) 0.740 1.366 (0.409~4.558) 0.612
  高 3.545 (1.497~8.396) 0.004 3.402 (1.231~9.399) 0.018 3.015 (0.893~10.181) 0.076
P值 0.003 0.014 0.060
图2 血清β2微球蛋白与局灶节段性肾小球硬化病变之间的直线关系
表4 亚组中分析血清β2微球蛋白与局灶节段性肾小球硬化病变的关系
特征 样本量 OR(95%CI) P值 P值(交互作用检验)
性别       0.133
  男 93 1.708 (1.088~2.680) 0.020  
  女 56 1.024 (0.595~1.765) 0.931  
民族       0.896
  汉 25 1.345 (0.482~3.751) 0.571  
  壮 103 1.407 (0.959~2.065) 0.081  
  其他 21 1.964 (0.472~8.174) 0.354  
年龄(岁)       0.323
  <50 74 1.273 (0.639~2.536) 0.492  
  ≥50 75 2.026 (1.137~3.611) 0.017  
高血压病史       0.002
  有 46 4.086 (1.512~11.043) 0.006  
  无 103 1.007 (0.647~1.567) 0.975  
体重指数       0.253
  <24 98 1.716 (1.108~2.657) 0.016  
  ≥24 51 0.945 (0.377~2.368) 0.904  
24 h尿蛋白定量(g)       0.448
  <3.5 48 1.263 (0.746~2.139) 0.385  
  ≥3.5 101 1.639 (1.041~2.579) 0.033  
萎缩纤维化       0.435
  是 96 1.619 (1.040~2.520) 0.033  
  否 53 1.004 (0.351~2.875) 0.994  
图3 血清β2微球蛋白水平预测膜性肾病患者局灶节段性肾小球硬化病变发生的作用(ROC曲线)
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