南方医科大学学报

南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (03): 387-.

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2型糖尿病肾病患者生长分化因子-15的表达及临床意义

李慧，高方，薛耀明，钱毅   

  • 出版日期:2014-03-20 发布日期:2014-03-20

Value of plasma growth differentiation factor-15 in diagnosis and evaluation of type 2
diabetic nephropathy

  • Online:2014-03-20 Published:2014-03-20

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摘要： 目的探讨生长分化因子-15（GDF-15）在2 型糖尿病肾病中的表达水平及其临床意义。方法纳入80 例2 型糖尿病
（T2DM）患者，根据Mogensen分期标准，分为正常白蛋白尿组（30例）、微量白蛋白尿组（20例）和大量白蛋白尿组（30例），采用
ELISA法测定血浆GDF-15水平。结果大量白蛋白尿组GDF-15水平高于微量白蛋白尿组和正常白蛋白尿组（P均<0.01），分
别为1773.9（1099.1~2357.4）pg/ml、864.0（636.1~994.3）pg/ml 和704.5（548.8~975.8）pg/ml；微量白蛋白尿组GDF-15水平高于
正常白蛋白尿组（P>0.05），且在肾功能轻度受损（60≤肾小球滤过率<90 ml/min/1.73 m2）时GDF-15 浓度即有增加，为999.5
（769.2~1372.1）pg/ml。偏相关分析显示，血浆GDF-15与糖尿病病程、尿微量白蛋白（mAlb）、尿素氮（BUN）及肌酐（sCr）呈正相
关（r=0.246，0.493，0.390，0.471，P均<0.05），与估计的肾小球滤过率（eGFR）及血浆白蛋白（Alb）呈负相关（r=-0.438，-0.397，P均
<0.01）。多元线性回归分析提示较高水平的GDF-15为mAlb增加的独立危险因素。在对肾功能受损（eGFR<90 ml/min/1.73 m2）
的诊断中，GDF-15和mAlb的曲线下面积分别为0.801和0.717，GDF-15曲线下面积大于mAlb（P<0.05）。当733.78 pg/ml 作为
GDF-15诊断肾功能受损的临界值时，敏感性和特异性达到最佳，分别为88.1%和58.1%。结论GDF-15在2型糖尿病肾病不同
临床阶段有不同程度的增高，不但与mAlb、eGFR有良好的相关性，而且是mAlb增加的独立危险因素，故在2型糖尿病肾病的
早期诊断、病情评估及预测其疾病转归方面具有一定的应用价值。

Abstract: Objective To detect the plasma level of growth differentiation factor-15 (GDF-15) in patients of type 2 diabetic
nepropathy and assess its value in diagnosis and evaluation of type 2 diabetic nepropathy. Methods Thirty type 2 diabetic
patients with normoalbuminuria, 20 with microalbuminuria, and 30 with macroalbuminuria, diagnosed according to
Mogensen’s criteria, were examined for plasma GDF-15 level using enzyme-linked immumosorbent assay. Results The
patients with macroalbuminuria had significantly higher plasma GDF-15 level than those with microalbuminuria and
normoalbuminuria [1773.9 (1099.1-2357.4) pg/ml vs 864.0 (636.1-994.3) pg/ml and 704.5 (548.8-975.8) pg/ml, respectively, P<
0.01], and patients with microalbuminuria had higher GDF-15 level than those with normoalbuminuria (P>0.05). Plasma
GDF-15 level was found to increase early in the stage of mild renal dysfunction (60≤GFR<90 ml·min-1·1.73 m-2) with a median
level of 999.5 (769.2-1372.1) pg/ml. Partial correlation analysis showed that plasma GDF-15 level was positively correlated with
diabetic durations, mAlb, BUN and sCr (r=0.246, 0.493, 0.390, and 0.471, respectively, P<0.05), and negatively with eGFR
(r=-0.438) and Alb (r=-0.397) (P<0.01). Multivariate linear regression analysis showed that a high plasma GDF-15 level was an
independent risk factor for increased mAlb. In the diagnosis of renal dysfunction (eGFR<90 ml·min-1·1.73 m-2), the area under
the receiver-operating characteristic curve (AUC) of GDF-15 was 0.801, significantly higher than that of mAlb (0.717, P<0.05).
With the cut-off value of 733.78 pg/ml, plasma GDF-15 level had a sensitivity of 88.1% and a specificity of 58.1% for renal
dysfunction diagnosis. Conclusion In patients with type 2 diabetic nephropathy, plasma GDF-15 level increases with the
Mogensen stage, and as a independent risk factor for increased mAlb, it is significantly correlated with mAlb and eGFR, and
serves, suggesting its value in early diagnosis, evaluation and prediction of the outcomes of type 2 diabetic nephropathy.