KLF4在糖尿病肾脏病Ⅲ~Ⅳ期肾精亏虚证中的表达和临床意义

Expression and clinical significance of KLF4 in stage III-IV diabetic kidney disease(DKD)with kidney essence deficiency

目的探讨尿液Krüppel样转录因子4(krüppel-like factor 4,KLF4)在糖尿病肾脏病(diabetic kidney disease,DKD)中的表达和临床意义,探寻KLF4与DKD肾精亏虚证的关联性。方法纳入2022年1月至2023年3月期间就诊于北京中医药大学附属东直门医院的符合诊断标准的Ⅲ~Ⅳ期DKD患者45例,2型糖尿病(type 2 diabetes mellitus,T2DM)患者56例及健康对照者44例,并依据中医证型诊断标准将DKD患者分为肾精亏虚证组27例和非肾精亏虚证组18例。分别比较受试者实验室指标及尿液KLF4的表达差异,Pearson相关性分析KLF4与DKD临床特征相关性,Logistic回归分析DKD危险因素,ROC曲线计算KLF4的诊断效能。结果DKD组尿液KLF4的表达水平低于健康对照组和T2DM组(P<0.05),相关性分析中DKD患者尿液KLF4表达水平与eGFR(r=0.378,P<0.05)呈正相关,与Scr(r=-0.358,P<0.05),CysC(r=-0.388,P<0.05)和24 h-UTP(r=-0.344,P<0.05)呈负相关。其中DKD肾精亏虚证组尿液KLF4表达水平低于非肾精亏虚证组(P<0.05),相关性分析中KLF4表达水平与肾精亏虚证候积分呈负相关(r=-0.323,P<0.05)。Logistic回归分析提示KLF4是DKD的保护因素,但ROC曲线显示诊断效能一般。结论DKD患者尤其肾精亏虚证患者存在尿液KLF4异常低表达,其可能成为非侵入性辅助诊断DKD的新型分子标志。

Objective To investigate the expression and clinical significance of KLF4 in the urine of patients with diabetic kidney disease(DKD),and to explore the relationship between KLF4 and the TCM pattern of kidney essence deficiency in DKD.Methods From January 2022 to March 2023,a total of 45 patients with stage III-IV DKD,56 patients with type 2 diabetes mellitus(T2DM),and 44 healthy controls were enrolled at Dongzhimen Hospital affiliated with Beijing University of Chinese Medicine.Based on the diagnostic criteria for kidney essence deficiency,the DKD patients were divided into two groups:27 cases with kidney essence deficiency and 18 cases without.Differences in laboratory parameters and urinary KLF4 expression were compared.The correlation between KLF4 and clinical characteristics of DKD was analyzed using Pearson correlation analysis,DKD risk factors were assessed via Logistic regression analysis,and the diagnostic efficacy of KLF4 was evaluated with ROC curves.Results The expression level of KLF4 in the urine of patients with DKD was lower than that of healthy control group and T2DM group(P<0.05),and the level of KLF4 in urine of patients with DKD was positively correlated with eGFR(r=0.378,P<0.05),negatively correlated with Scr(r=-0.358,P<0.05),CysC(r=-0.388,P<0.05)and 24 h-UTP(r=-0.344,P<0.05)in correlation analysis.The expression level of KLF4 in urine of kidney-essence deficiency group was lower than that of non-kidney-essence deficiency group,which was negatively correlated with the score of kidney essence deficiency syndrome(r=-0.323,P<0.05).Logistic regression analysis suggested that KLF4 was a protective factor for DKD,but the diagnostic performance was generally moderate.Conclusion DKD patients,especially those with kidney essence deficiency,have abnormally low levels of urinary expression of KLF4.This finding suggests that KLF4 could potentially serve as a novel molecular marker for the non-invasive auxiliary diagnosis of DKD.