六种肾小球滤过率估算公式用于多发性骨髓瘤患者肾功能评估的一致性分析

Comparison of estimated glomerular filtration rates in patients with multiple myeloma among six equations

目的系统评价不同估算肾小球滤过率(eGFR)公式用于多发性骨髓瘤(MM)患者肾功能评估的一致性,初步筛选出更适合中国MM患者的eGFR公式。方法收集372例确诊为MM的患者,检测其血清游离轻链(FLC)水平及血清尿素(Sur)、肌酐(Scr)、尿酸(UA)、胱抑素C(CysC)及总钙(Ca)水平。利用肾脏病膳食改善(MDRD)公式、MDRD中国改良公式(MDRD-C)、慢性肾脏病流行病合作工作组(CKD-EPI)公式、中国CysC简化(CysC-C)公式、及慢性肾脏病流行病合作工作组推荐的CysC公式(CysC-K)及Scr和CysC联合(Cr-CysC)公式计算患者的eGFR。利用Bland-Altman图、κ一致性分析、Box-whisker图等进行相互比较,并研究FLC,UA等因素与不同公式间eGFR差值的相关性。结果①各指标中仅Scr及UA水平在不同性别的患者间的差异具有统计学意义(P<0.01)。Pearson相关分析表明Sur、Scr、CysC、UA和Ca与FLC差值的常用对数值(lgd-FLC)间的相关性均高于lgFLC-κ/λ值。②与CKD-EPI公式相比,MDRD和MDRD-C的eGFR值整体偏高,而CysC-C、CysC-K和Cr-CysC整体偏低,其中MDRD-C最高,而CysC-K最低。Cr-CysC与CKD-EPI公式间的平均偏差及SD最小。③MDRD、MDRD-C、Cr-CysC、CysC-C及CysC-K公式对患者的肾病分期与CKD-EPI公式的一致性加权κ值分别为0.955,0.933,0.719,0.477及0.533(均P<0.001)。相比CKD-EPI公式,MDRD和MDRD-C倾向于降低患者的CKD分期,而Cr-CysC及CysC-K公式则相反。CysC-C公式倾向于将早期CKD患者分为较高的分期,但却倾向于将晚期患者分为较低的分期。④对于1-2期肾病患者,MDRD-C公式的eGFR值最高,CysC-C及CysC-K公式的eGFR值最低(均P<0.001);对于4-5期的患者,CysC-C公式的eGFR值最高(P<0.001)。⑤除Scr和CysC外,lgd-FLC与不同eGFR计算值间的差值的偏相关性较高,而UA则与三种基于Scr的eGFR计算值间的差值的偏相关性较高。结论Cr-CysC公式对MM患者GFR的估算值与目前指南推荐的CKD-EPI公式一致性高,且更为灵敏。对早期患者,可考虑优先使用Cr-CysC公式进行肾功能评估。

Objective To systematically evaluate the consistencies of different equations for estimating glomerular filtration rate(eGFR)in patients with multiple myeloma(MM),and preliminarily screen a suitable equation for Chinese MM patients.Methods A total of 372 patients with MM were enrolled in this study.Serum levels of free light chain(FLC),urea(Sur),creatinine(Scr),uric acid(UA),cystatin C(CysC)and total calcium(Ca)were detected.Modification of diet in renal disease(MDRD)equation,modified MDRD equation for the Chinese population(MDRD-C),Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)equation,Chinese simplified CysC(CysC-C)equation,CysC equation suggested by the Kidney Disease:Improving Global Outcomes(KDIGO)guidelines(CysC-K),and the equation based on both Scr and CysC proposed by the KDIGO guidelines(Cr-CysC)were used to estimate the GFR values.The agreements among these equations were investigated using Bland-Altman plots,κstatistic,and Box-whisker plots.Relationship between FLC,UA,other factors and the eGFR difference between different equations was studied by Pearson and partial correlation.Results①Among all of the indicators,only Scr and UA levels showed statistical difference between male and female(P<0.01).Pearson correlation showed that the correlation coefficient between Sur,Scr,CysC,UA,Ca and the lg value of FLC difference(lgd-FLC)were higher than lgFLC-κ/λ.②The eGFR estimated by MDRD and MDRD-C was higher than that of CKD-EPI equation,while eGFR by CysC-C,CysC-K and Cr-CysC were lower.The eGFR was the highest by MDRD-C and the lowest by CysC-K.Bias and SD between Cr-CysC and CKD-EPI equations were the lowest.③Theκagreements between MDRD,MDRD-C,Cr-CysC,CysC-C and CysC-K equations and CKD-EPI equation on chronic kidney disease(CKD)staging were 0.955,0.933,0.719,0.477 and 0.533,respectively(P<0.001).Compared with CKD-EPI equation,MDRD and MDRD-C equations tended to degrade the CKD staging of patients,while Cr-CysC and CysC-K equations were the opposite.The CysC-C equation tended to assign patients with early stages of CKD to higher stages,but assign patients with late stages of CKD to lower stages.④For patients in early CKD stages,eGFR values by MDRD-C equation were the highest,while those were the lowest by CysC-C and CysC-K equations(P<0.001).For patients in late CKD stages,the eGFR values by CysC-C equation were the highest(P<0.001).⑤Except for the indexes of Scr and CysC,the partial correlations between lgd-FLC and the differences between five eGFR values were higher.Besides,the partial correlations between UA and the differences between three Scr-based eGFR values were also higher.Conclusion The eGFR estimated by Cr-CysC equation is more consistent with that of CKD-EPI equation recommended by the current guidelines,and Cr-CysC equation has higher sensitivity.The Cr-CysC equation may be more suitable for eGFR evaluation in patients with early MM-related kidney injury.