血游离轻链与M蛋白检测在膜性肾病合并MGUS患者中的临床意义

Clinical significance of serum free light chains combined with M-protein in patients with membranous nephropathy and monoclonal gammopathy of undetermined significance

目的探讨血游离轻链(sFLC)与M蛋白检测在膜性肾病(MN)合并意义未明单克隆免疫球蛋白血症(MGUS)患者中的临床意义。方法研究采用前瞻性设计,纳入2021年1月至2023年10月在西安交通大学第一附属医院榆林医院诊治的82例MN患者,根据是否合并MGUS分为MN组(53例)和merge组(29例)。merge组男18例、女11例,年龄(52.64±7.33)岁;MN组男33例、女20例,年龄(55.35±6.89)岁。采用血清学检测方法对患者进行sFLC[κ轻链(sFLCκ)、λ轻链(sFLCλ)]与M蛋白检测,并通过logistic回归分析探讨其与MN合并MGUS的关系,并使用受试者操作特征曲线(ROC)检测sFLC联合M蛋白在MN合并MGUS诊断中的性能。统计学方法采用t检验、χ^(2)检验。结果merge组红细胞沉降率(ESR)、血清肌酐(Scr)、C反应蛋白(CRP)和血尿素氮(BUN)指标均高于MN组[(48.52±5.65)mm/h比(36.34±4.35)mm/h、(84.51±10.26)μmol/L比(72.65±8.25)μmol/L、(2.18±0.64)mg/L比(1.26±0.35)mg/L、(6.45±1.27)mmol/L比(5.12±1.12)mmol/L],差异均有统计学意义(t=10.884、5.702、8.434、4.902,均P<0.05)。merge组阳性率为96.55%(28/29),高于MN组的3.77%(2/53),差异有统计学意义(χ^(2)=69.543,P<0.05)。merge组sFLCκ水平及sFLCκ/λ比值均高于MN组[(453.51±123.57)mg/L比(62.84±100.25)mg/L、(15.89±2.84)比(1.11±0.26)],sFLCλ水平低于MN组[(28.54±23.84)mg/L比(56.77±18.35)mg/L],差异均有统计学意义(t=15.520、37.791、5.979,均P<0.05)。相关性分析结果显示,sFLCκ、sFLCκ/λ比值与肾功能损害及炎症水平有显著相关性,而sFLCλ相关性相对较弱。逻辑回归分析显示,sFLCκ、sFLCκ/λ比值对诊断具有显著影响,而sFLCλ具有负向影响。ROC分析显示,sFLC联合M蛋白进行诊断时,灵敏度为96.6%,特异度为77.4%,约登指数为73.9%,曲线下面积为0.933,95%CI 0.884~0.982。结论sFLC与M蛋白检测对于MN合并MGUS患者的诊断和疾病活动度评估具有重要临床意义,与肾功能损害程度密切相关,可为监测和治疗效果评估提供重要参考。

Objective To explore the clinical significance of serum free light chains(sFLC)and M-protein in patients with membranous nephropathy(MN)and monoclonal gammopathy of undetermined significance(MGUS).Methods A prospective study design was employed.Eighty-two patients with MN treated at Yulin Hospital,First Hospital,Xi'an Jiaotong University from January 2021 to October 2023 were selected,and were divided into an MN group(53 cases)and a merge group(29 cases)according to whether they were combined with MGUS.There were 18 males and 11 females in the merge group;they were(52.64±7.33)years old.There were 33 males and 20 females in the MN group;they were(55.35±6.89)years old.The serological testing methods were used to detect the sFLC(sFLCκand sFLCλ)and M-protein in these patients.Logistic regression analysis was used to explore their relationship with MN combined with MGUS,and the receiver operating characteristic curve(ROC)was used to test the diagnostic performance of sFLC combined with M-protein for MN combined with MGUS.t andχ^(2) tests were applied.Results The erythrocyte sedimentation rate(ESR),serum creatinine(Scr),C-reactive protein(CRP),and blood urea nitrogen(BUN)in the merge group were higher than those in the MN group[(48.52±5.65)mm/h vs.(36.34±4.35)mm/h,(84.51±10.26)μmol/L vs.(72.65±8.25)μmol/L,(2.18±0.64)mg/L vs.(1.26±0.35)mg/L,and(6.45±1.27)mmol/L vs.(5.12±1.12)mmol/L],with statistical differences(t=10.884,5.702,8.434,and 4.902;all P<0.05).The positive rate in the merge group was higher than that in the MN group[96.55%(28/29)vs.3.77%(2/53)],with a statistical difference(χ^(2)=69.543;P<0.05).The level of sFLCκand sFLCκ/λratio in the merge group were higher than those in the MN group[(453.51±123.57)mg/L vs.(62.84±100.25)mg/L and(15.89±2.84)vs.(1.11±0.26)];the level of sFLCλin the merge group was lower than that in the MN group[(28.54±23.84)mg/L vs.(56.77±18.35)mg/L];there were statistical differences(t=15.520,37.791,and 5.979;all P<0.05).The correlation analysis showed that sFLCκand sFLCκ/λratio were significantly correlated with renal impairment and inflammation level,while sFLCλhad relatively weaker correlation.The logistic regression analysis indicated that sFLCκand sFLCκ/λratio significantly influenced diagnosis,whereas sFLCλhad a negative impact.The ROC analysis demonstrated that sFLC combined with M-protein for the diagnosis had a sensitivity of 96.6%,a specificity of 77.4%,a Youden's index of 73.9%,and an area under the curve(AUC)of 0.933,with a 95%confidence interval(CI)of 0.884 to 0.982.Conclusions The detection of sFLC and M-protein is of significant clinical importance for the diagnosis and assessment of disease activity in patients with MN and MGUS.They are closely related to the degree of kidney function damage and can serve as important references for monitoring and assessing treatment efficacy.