SFRP1、GDF-15、RBP联合检测在糖尿病肾病早期诊断及预后中的价值OA
Value of combined detection of SFRP1,GDF-15,and RBP in the early diagnosis and prognosis of diabetic kidney disease
目的:糖尿病肾病(diabetic kidney disease,DKD)是2型糖尿病(type 2 diabetes mellitus,T2DM)常见的微血管并发症之一,也是终末期肾病的主要危险因素.目前尿微量白蛋白(urine microalbumin,mAlb)是DKD早期筛查的常用指标,但其敏感性及预后评估存在一定的局限,因此亟需寻找更有效的新型生物标志物.分泌型卷曲相关蛋白1(secreted frizzled-related protein 1,SFRP1)、生长分化因子-15(growth differentiation factor-15,GDF-15)及视黄醇结合蛋白(retinol-binding protein,RBP)已被证实参与糖尿病及其并发症的发生、发展,但其在DKD中的临床应用价值尚待验证.本研究探究SFRP1、GDF-15、RBP在DKD早期诊断及预后中的价值.方法:选取2023年7月至2024年6月在张家港市第一人民医院就诊的100例T2DM患者,根据尿白蛋白与肌酐比值(urinary albumin-to-creatinine ratio,UACR)分为对照组(UACR<30 mg/g,n=50)和观察组(UACR 30~300 mg/g,n=50).采用双抗体夹心酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)测定血清GDF-15水平,ELISA法检测血清SFRP1水平,免疫比浊法测定尿RBP水平.将随访2年期间估计肾小球滤过率(estimated glomerular filtration rate,eGFR)下降≥15%或开始肾脏替代治疗定义为预后不良,根据随访结局将观察组患者分为预后良好亚组与预后不良亚组,比较2亚组患者基线及2年随访时SFRP1、GDF-15、RBP水平的变化情况.采用受试者操作特征(receiver operating characteristic,ROC)曲线评估SFRP1、GDF-15、RBP单独及联合检测对DKD的诊断效能,以及24 h mAlb单独及联合SFRP1、GDF-15、RBP对DKD患者预后不良的预测效能.结果:观察组患者的血清SFRP1水平显著低于对照组,而血清GDF-15水平及尿RBP水平均显著高于对照组(均P<0.05).ROC曲线显示,血清SFRP1、血清GDF-15、尿RBP均有良好的DKD诊断效能,三者联合诊断效能更佳,曲线下面积(area under the curve,AUC)为0.980(95%CI 0.929~0.997,均P<0.001).预后良好亚组患者基线时血清SFRP1水平高于预后不良亚组患者,而尿RBP水平、血清GDF-15水平均低于预后不良亚组患者(均P<0.05).且预后不良组亚组患者随访2年时血清SFRP1水平更低,血清GDF-15水平、尿RBP水平更高,2亚组患者基线与2年随访时各指标的比较,差异均有统计学意义(均P<0.05).24 h mAlb预测DKD患者随访2年预后不良的AUC为0.729(95%CI 0.585~0.845),同时联合SFRP1、GDF-15、RBP可将预测DKD患者随访2年预后不良的AUC增加至0.862(95%CI 0.735~0.943).结论:血清SFRP1、血清GDF-15、尿RBP可作为DKD的新型诊断标志物,三者联合24 h mAlb对DKD患者的预后具有较高的预测效能.
Objective:Diabetic kidney disease(DKD)is one of the common microvascular complications of type 2 diabetes mellitus(T2DM)and a major risk factor for end-stage renal disease(ESRD).Currently,urine microalbumin(mAlb)is commonly used for early screening of DKD;however,its sensitivity and prognostic value are limited.Therefore,there is an urgent need to identify more effective novel biomarkers.Secreted frizzled-related protein 1(SFRP1),growth differentiation factor-15(GDF-15),and retinol-binding protein(RBP)have been shown to be involved in the occurrence and development of diabetes and its complications,but their clinical value in DKD remains to be elucidated.This study aims to investigate the value of SFRP1,GDF-15,and RBP in the early diagnosis and prognosis of DKD. Methods:A total of 100 patients with T2DM who visited Zhangjiagang Hospital from July 2023 to June 2024 were selected.According to the urinary albumin-to-creatinine ratio(UACR),patients were divided into a control group(UACR<30 mg/g,n=50)and an observation group(UACR 30-300 mg/g,n=50).Serum GDF-15 levels were measured using a double-antibody sandwich enzyme-linked immunosorbent assay(ELISA),serum SFRP1 levels were measured by ELISA,and urinary RBP levels were measured by immunoturbidimetry.Poor prognosis was defined as a decline in estimated glomerular filtration rate(eGFR)≥15%or initiation of renal replacement therapy during the 2-year follow-up period.According to follow-up outcomes,patients in the observation group were further divided into a good prognosis subgroup and a poor prognosis subgroup.Changes in SFRP1,GDF-15,and RBP levels at baseline and after 2 years were compared between the 2 subgroups.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of SFRP1,GDF-15,and RBP alone and in combination for DKD,as well as the predictive performance of 24 h mAlb alone and in combination with SFRP1,GDF-15,and RBP for poor prognosis in patients with DKD. Results:The serum SFRP1 level in the observation group was significantly lower than that in the control group,whereas the serum GDF-15 level and urinary RBP level were significantly higher than those in the control group(P<0.05).ROC curve analysis showed that serum SFRP1,serum GDF-15,and urinary RBP all had good diagnostic performance for DKD,and their combined detection showed superior performance,with an area under the curve(AUC)of 0.980(95%CI 0.929 to 0.997,P<0.001).At baseline,patients in the good prognosis subgroup had higher serum SFRP1 levels and lower urinary RBP and serum GDF-15 levels than those in the poor prognosis subgroup(all P<0.05).After the 2-year follow-up,patients in the poor prognosis subgroup had lower serum SFRP1 levels and higher serum GDF-15 and urinary RBP levels.Comparisons of these indicators between baseline and 2-year follow-up in both subgroups showed statistically significant differences(P<0.05).The AUC of 24 h mAlb for predicting poor prognosis in patients with DKD over 2 years was 0.729(95%CI 0.585 to 0.845).and when combined with SFRP1,GDF-15,and RBP,the AUC increased to 0.862(95%CI 0.735 to 0.943). Conclusion:Serum SFRP1,serum GDF-15,and urinary RBP may serve as novel diagnostic biomarkers for DKD.Their combination with 24 h mAlb provides higher predictive performance for prognosis in patients with DKD.
倪文慧;钱文娟
张家港市第一人民医院肾内科,苏州 215600张家港市第一人民医院肾内科,苏州 215600
医药卫生
2型糖尿病糖尿病肾病分泌型卷曲相关蛋白1生长分化因子-15视黄醇结合蛋白
type 2 diabetes mellitusdiabetic kidney diseasesecreted frizzled-related protein 1growth differentiation factor-15retinol-binding protein
《临床与病理杂志》 2026 (1)
29-36,8
张家港市青年科技项目(ZJGQNKJ202205).This work was supported by the Zhangjiagang City Youth Science and Technology Project,China(ZJGQNKJ202205).
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