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

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

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(OR1.421,95%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(OR4.086,95%CI:1.512~11.043),而无高血压病史的患者未发现统计学关联(OR1.007,95%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(OR4.711,95%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。

Objective To explore the relationship between serumβ2 microglobulin and the lesion of focal segmental glomerulosclerosis(FSGS)in patients with idiopathic membranous nephropathy(IMN).MethodsThis 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 serumβ2 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 serumβ2 microglobulin and the FSGS lesion.The generalized additive model(GAM)was used to explore the nonlinear relationship between serumβ2 microglobulin and the FSGS lesion.In addition,the relationship between serumβ2 microglobulin and the FSGS lesion in different subgroups was also analyzed.ResultsAfter 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 serumβ2 microglobulin was an independent risk factor for the occurrence of FSGS lesion(OR1.421,95%CI:1.002-2.014,P=0.049).GAM analysis found that the relationship between serumβ2 microglobulin and the FSGS lesion was linear.The results of subgroup analysis suggested that the relationship between serumβ2 microglobulin and the FSGS lesion was enhanced in patients with a history of hypertension(OR4.086,95%CI:1.512-11.043),but not in patients without a history of hypertension(OR1.007,95%CI:0.647-1.567)(P=0.975).ROC curve analysis showed that serumβ2 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 serumβ2 microglobulin<2.65 mg/L,the occurrence risk of FSGS lesion increased by 3.7 times(OR4.711,95%CI:1.732-12.812,P=0.002)in patients with both a history of hypertension and the serumβ2 microglobulin≥2.65 mg/L.ConclusionThe increase of serumβ2 microglobulin was closely related to FSGS lesion occurrence in IMN patients.In patients with a history of hypertension the influence of serumβ2 microglobulin on FSGS lesion occurrence was enhanced.