肾小球滤过率、尿微量白蛋白、血β2-微球蛋白和胱抑素C诊断糖尿病肾病的临床价值

Diagnostic value of glomerular filtration rate, microalbuminuria, β2-microglobulin and cystatin C for renal function in patients with diabetic nephropathy

目的 探讨GFR、尿微量白蛋白（mAlb）、血β2-微球蛋白（MG）和胱抑素C（CysC）诊断DN的临床价值.方法 经WHO 1999年糖尿病诊断和分型标准确诊的2型DM患者150例（2012年12月至2015年12月）,以同期肾移植供体33例为健康对照组.分别检测尿mAlb、Cr、白蛋白/Cr比值（ACR）、SCr、β2-MG、CysC、尿素、尿酸（UA）、空腹血糖（FBG）、糖化血红蛋白（HbA1c）、C-反应蛋白（CRP）.行99Tcm-DTPA肾动态显像,用Gates法测得GFR,同步用简化肾脏病膳食改良试验（MDRD）公式计算估算GFR（eGFR）,推导GFR和eGFR之间的相关性及回归方程.采用Mogenesen标准法对2型DM患者的肾功能进行临床分期,依UA、CRP值的高低进行分组,用两样本t检验分析各指标的差异.利用ROC曲线分析GFR诊断DN各期的价值.结果 150例患者分为单纯DM组、DN早期（Ⅰ、Ⅱ、Ⅲ期）组和DN临床期（Ⅳ期）组.DNⅠ期仅GFR和eGFR高于单纯DM组（t值：-7.502和-3.629,均P＜0.01）.DN进展到Ⅱ、Ⅲ及Ⅳ期时,GFR和eGFR相继明显下降,而血UA、CRP、FBG和HbA1c明显升高, SCr、尿素、β2-MG、CysC和尿mAlb、ACR等肾功能指标也明显升高.GFR与eGFR间呈明显直线相关,回归方程为：y=0.957x＋6.823.ROC曲线分析GFR诊断DNⅠ期的AUC为0.989,诊断阈值为125.09 ml/min,灵敏度为96.2%（25/26）、特异性为98.4%（122/124）.高UA组与UA正常组相比,FBG和HbA1c差异无统计学意义（t值：-1.010、-1.034,均P＞0.05）,而各项肾功能指标差异均有统计学意义（t值：-5.090~2.209,均P＜0.01）.高CRP组与CRP正常组相比,FBG、HbA1c和各项肾功能指标差异均有统计学意义（t值：-6.114~7.386,均P＜0.01）.结论 2型DM中,GFR与eGFR间呈明显直线相关.ROC曲线分析GFR是诊断DNⅠ期的灵敏和特异指标.血β2-MG、CysC和尿mAlb、ACR的检测有利于DN早期的诊断.UA是DN发病的独立危险因子,CRP是2型DM引起DN的致炎损伤因子.

Objective To investigate the clinical value of GFR, microalbuminuria （mAlb）, serum β2-microglobulin （MG） and cystatin C （CysC） for the evaluation of renal function in patients with DN.Methods A total of 150 patients with type 2 DM diagnosed by WHO standard （1999） from December 2012 to December 2015 were retrospectively analyzed.Thirty-three kidney transplantation donors during the same time were chosen as the control group.The urine mAlb, Cr, albumin/Cr ratio（ACR） and SCr, serum β2-MG, CysC, urea, uric acid（UA）, fasting blood glucose （FBG）, hemoglobin A lc （HbA1c） and C-reactive protein （CRP） were measured.99Tcm-DTPA renal dynamic imaging was performed.The Gates method was used to calculate GFR, and the modification of diet in renal disease （MDRD） method was used to calculate the estimated GFR （eGFR）.The relative equation between GFR and eGFR was studied.The clinical stages of renal function in type 2 DM patients were evaluated by Mogenesen standard method.Two-sample t test was used for data analysis.ROC curve analysis was performed to study the diagnostic value of GFR in DN.Results The patients were divided into merely type 2 DM group, early stage DN （Ⅰ, Ⅱ, Ⅲ）, and clinical DN（Ⅳ） groups by Mogenesen standard method.GFR and eGFR in the DNⅠstage were higher than those of the merely type 2 DM group （t values：-7.502,-3.629, both P〈0.01）, and GFR and eGFR decreased with the increased stage of DN.However, serum UA, CRP, FBG and HbA1c, SCr, urea, β2-MG, CysC, mAlb and ACR increased when the stage of DN was higher.GFR and eGFR showed a linear correlation, with the regression equation of y=0.957x＋6.823.AUC of ROC in patients with DN Ⅰ was 0.989.With the cutoff value of 125.09 ml/min, the sensitivity and specificity was 96.2%（25/26） and 98.4%（122/124） respectively in diagnosis of DNⅠ.Between high UA and normal UA groups, FBG and HbA1c were not significantly different （t values：-1.010,-1.034, both P〉0.05）, but the renal function indicators were different （t values：-5.090-2.209, all P〈0.01）.Compared with the normal CRP group, the FBG, HbA1c and renal function indicators were statistically different in high CRP group （t values：-6.114-7.386, all P〈0.01）.Conclusions GFR and eGFR show a linear relationship in type 2 DM.GFR is a sensitive, specific diagnostic index in DN Ⅰ period.β2-MG, CysC, mAlb and ACR are conducive to the early diagnosis of DN.High UA is an independent risk factor for the onset of DN, and high CRP is an inflammatory damage factor in DN.