多发性骨髓瘤合并肾损伤患者的临床特点及危险因素分析

Clinical characteristics and risk factors of multiple myeloma patients with renal impairment

目的探讨多发性骨髓瘤(MM)患者肾损伤的临床特征、细胞遗传学特点及其危险因素。方法回顾性分析2013年1月至2017年12月武汉大学中南医院肾内科和血液内科收治的113例初诊MM患者的临床资料,以患者确诊时血肌酐是否>177μmol/L为标准分为肾损伤组和非肾损伤组,比较两组患者的一般资料和实验室检查结果,采用二元Logistic回归法分析MM患者发生肾损伤的危险因素,绘制受试者工作特征曲线(ROC),评估各危险因素对MM患者发生肾损伤的预测价值。结果113例MM患者中肾损伤的发生率为34.5%。肾损伤组(n=39)白细胞、血尿酸、血尿素氮、中性粒细胞/淋巴细胞比值(NLR)、胱抑素C、β2微球蛋白(β2-MG)、血磷、尿轻链、骨髓浆细胞比例、国际分期体系(ISS)-III期比例、轻链型比例、尿本周蛋白阳性比例及尿蛋白阳性比例均高于非肾损伤组(n=74),而估算肾小球滤过率、血碳酸氢根浓度、球蛋白低于非肾损伤组(均P<0.05),两组其他临床特征差异无统计学意义(均P>0.05)。其中42例MM患者对IgH(免疫球蛋白重链)重排、1q21(1号染色体长臂2区1带)扩增、RB1(视网膜母细胞瘤基因1)缺失、D13S319(13号染色体长臂1区4带的D13S319位点)缺失、P53(位于17号染色体短臂1区3带的一种抑癌基因)缺失5种遗传学异常行荧光原位杂交(FISH)检测,29例(69.0%)检测结果异常。肾损伤组RB1缺失发生率高于非肾损伤组(P<0.05),其他基因异常发生率差异无统计学意义(均P>0.05)。进一步Logistic回归分析结果显示,NLR升高(OR=1.589,95%CI 1.115~2.266,P=0.010)、骨髓浆细胞比例升高(OR=1.053,95%CI 1.008~1.101,P=0.021)、β2-MG升高(OR=22.166,95%CI 2.146~228.927,P=0.009)、轻链型(OR=15.399,95%CI 1.002~236.880,P=0.049)和高尿酸血症(OR=11.707,95%CI 1.580~86.717,P=0.016)是MM患者发生肾损伤的独立危险因素。各危险因素间的ROC曲线下面积(AUC)比较结果显示,β2-MG曲线下面积大于NLR、尿酸(均P<0.05),而其余两两因素间比较差异无统计学意义(均P>0.05)。β2-MG预测MM患者发生肾损伤的AUC最大(AUC=0.907,95%CI 0.853~0.962,P<0.001)。结论MM患者中肾损伤发病率较高,肾损伤患者存在RB1缺失者较多。轻链型、高尿酸血症和高NLR、高骨髓浆细胞比例、高β2-MG水平是MM患者发生肾损伤的独立危险因素,其中β2-MG是预测MM肾损伤发生的最佳预测因子。NLR作为一个方便而有效的炎性指标,对预测MM肾损伤有重要意义。

Objective To explore the clinical and cytogenetic characteristics and risk factors of multiple myeloma(MM)patients with renal impairment(RI).Methods A total of 113 newly diagnosed patients with MM in the department of nephrology and hematology in Zhongnan Hospital of Wuhan University from January 2013 to December 2017 were enrolled.The patients were divided into RI group and non-renal impairment(NRI)group according to whether serum creatinine(Scr)at the time of diagnosis was higher than 177μmol/L.The clinical and laboratory data of two groups were compared.The risk factors of RI in MM patients were analyzed by binary logistic regression,and then the receiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of these risk factors.Results The incidence of RI in 113 MM patients was 34.5%.Compared with NRI group,levels of white blood cells,serum uric acid,blood urea nitrogen,neutrophil-to-lymphocyte ratio(NLR),cystatin C,β2-microglobulin(β2-MG),blood phosphorus,urine light chain,bone-marrow plasma cell percentage,International Staging System(ISS)stage III percentage,light chain type percentage,positive urinary Bence-Jones protein percentage and positive urinary protein percentage were higher in RI group,while levels of estimated glomerular filtration rate(eGFR),serum bicarbonate concentration and globulin were lower in RI group(all P<0.05).There were no significant differences in other clinical variables between the two groups(all P>0.05).Fluorescence in situ hybridization(FISH)was applied to 42 MM patients to detect the following five genetic abnormalities:IgH rearrangement,1q21 amplification,RB1 deletion,D13S319 deletion and P53 deletion.Among them,29(69.0%)patients were abnormal.The incidence of RB1 deletion in RI group was higher than NRI group(P<0.05),and there were no significant differences in the incidences of other genetic abnormalities(all P>0.05).Further logistic regression analysis showed that increase of NLR(OR=1.589,95%CI 1.115-2.266,P=0.010),bone-marrow plasma cell percentage(OR=1.053,95%CI 1.008-1.101,P=0.021)andβ2-MG(OR=22.166,95%CI 2.146-228.927,P=0.009),light chain type(OR=15.399,95%CI 1.002-236.880,P=0.049),and hyperuricemia(OR=11.707,95%CI 1.580-86.717,P=0.016)were the independent risk factors for RI in MM patients.The comparison of area under the ROC(AUC)among these risk factors showed the AUC ofβ2-MG was larger than that of NLR or uric acid(both P<0.05),while there were no significant differences in the rest of pairwise comparison(all P>0.05).The AUC ofβ2-MG predicting RI was the largest(AUC=0.907,95%CI 0.853-0.962,P<0.001).Conclusions MM patients have high morbidity of RI,and there are more RI patients with RB1 deletion in RI patients.Light chain type,hyperuricemia,high level of NLR,high bone-marrow plasma cell percentage and increasedβ2-MG are the independent risk factors for RI in MM patients.Among them,β2-MG is the best predictor for RI,and NLR plays an important role in predicting RI as a convenient and effective inflammatory marker.