摘要
目的 探讨血清长链非编码RNA(LncRNA)无远端同源框6反义RNA 1(Dlx6os1)、LncRNA牛磺酸上调基因1(TUG1)水平与老年糖尿病肾病(DN)患者肾脏损伤及预后的相关性.方法 选取2019年1月—2021年1月西安交通大学第一附属医院榆林医院肾病学科收治的老年DN患者201例作为DN组,同期单纯T2DM患者112例作为单纯T2DM组,同期体检健康的老年人105例作为健康对照组,随访3年根据预后将老年DN患者分为不良预后亚组(61例)和良好预后亚组(140例).检测血清LncRNA Dlx6os1、LncRNA TUG1和肾脏损伤指标[计算肾小球滤过率(eGFR)、尿白蛋白肌酐比(UACR)]水平;采用Spearman相关系数分析血清LncRNA Dlx6os1、LncRNA TUG1水平与老年DN患者肾损伤的相关性;以老年DN患者预后为因变量,建立多因素非条件Logistic回归模型分析其影响因素,并绘制受试者工作特征(ROC)曲线评价血清LncRNA Dlx6os1、LncRNA TUG1水平对其的预测价值.结果 健康对照组、单纯T2DM组、DN组血清LncRNA Dlx6os1和UACR水平依次升高,血清LncRNA TUG1和eGFR依次降低(F/P=870.484/＜0.001、566.671/＜0.001、271.117/＜0.001、196.722/＜0.001);Spearman 相关性显示,老年 DN 患者血清LncRNA Dlx6os1 水平与 eGFR 呈负相关、与 UACR 呈正相关(r/P=-0.816/＜0.001、0.809/＜0.001),血清 LncRNA TUG1水平与eGFR呈正相关、与UACR呈负相关(r/P=0.832/＜0.001、-0.806/＜0.001);随访截至2024年1月,老年DN患者201例不良预后发生率为30.35％(61/201);多因素非条件Logistic回归显示,慢性肾脏病≥4期、UACR升高、LncRNA Dlx6os1升高为老年DN患者不良预后的独立危险因素[OR(95％CI)=5.758(1.480～22.401)、1.013(1.005～1.022)、1.426(1.201～1.693)],eGFR 升高、LncRNA TUG1 升高为保护因素[OR(95％CI)=0.958(0.939～0.978)、0.418(0.254～0.689)];ROC 曲线显示,血清 LncRNA Dlx6os1、LncRNA TUG1 及二者联合预测老年 DN 患者不良预后的 AUC 分别为 0.774、0.777、0.852,二者联合预测的 AUC 最大(Z/P=2.930/0.003、3.335/0.001).结论 老年DN患者血清LncRNA Dlx6os1水平升高、LncRNA TUG1水平降低,与肾脏损伤加重和不良预后风险增加有关,血清LncRNA Dlx6os1联合LncRNA TUG1水平预测老年DN患者不良预后的效能较高.
Abstract
Objective To investigate the correlation between serum long non-coding RNA(LncRNA)distal-less homeobox6 antisense RNA 1(Dlx6os1),LncRNA taurine up-regulated gene 1(TUG1)levels and renal injury and prognosis in elderly diabetic nephropathy(DN)patients.Methods Two hundred and one elderly DN patients admitted to the Depart-ment of Nephrology,Yulin Hospital,the First Affiliated Hospital of Xi'an Jiaotong University from January 2019 to January 2021 were selected as the DN group,112 patients with pure T2DM during the same period as the pure T2DM group,and 105 healthy elderly people with physical examination during the same period as the control group,and the elderly DN pa-tients were divided into a poor prognosis subgroup(61 cases)according to the 3-year prognosis and a good prognosis subgroup(140 cases).The levels of serum LncRNA Dlx6os1,LncRNA TUG1 and renal injury indicators[estimated glomeru-lar filtration rate(eGFR),urinary albumin creatinine ratio(UACR)]were detected;the correlation between the levels of serum LncRNA Dlx6os1 and LncRNA TUG1 and renal injury of the elderly patients with DN was analyzed using Spearman's corre-lation coefficient;a multifactorial unconditional Logistic regression model to analyze the influence factors with the elderly DN patients'prognosis as the dependent variable,a multifactorial unconditional Logistic regression model was established to an-alyze the influencing factors,and the predictive value of serum LncRNA Dlx6os1 and LncRNA TUG1 levels was evaluated by plotting the receiver operating characteristics(ROC)curves.Results Serum LncRNA Dlx6os1 and UACR levels were se-quentially increased and serum LncRNA TUG1 and eGFR were sequentially decreased in the control,T2DM-only,and DN groups(F/P=870.484/＜0.001,566.671/＜0.001,271.117/＜0.001,196.722/＜0.001);Spearman's correlation showed that serum LncRNA Dlx6os1 levels were negatively correlated with eGFR and positively correlated with UACR in elderly DN patients(r/P=-0.816/＜0.001,0.809/＜0.001),and serum LncRNA TUG1 levels were positively correlated with eGFR and negatively cor-related with UACR(r/P=0.832/＜0.001,-0.806/＜0.001);Follow-up as of January 2024,the incidence of poor prognosis in 201 cases of elderly DN patients was 30.35％(61/201);multifactorial unconditional logistic regression showed that chronic kidney disease stage 4,high UACR,and high LncRNA Dlx6os1 were the independent risk factors for poor prognosis in eld-erly DN patients[OR(95％CI)=5.758(1.480-22.401),1.013(1.005-1.022),1.426(1201-1.693)],and high eGFR and high Ln-cRNA TUG1 were the independent protective factors[OR(95％CI)=0.958(0.939-0.978),0.418(0254-0.689)];ROC curves showed that the AUCs of serum LncRNA Dlx6os1,LncRNA TUG1,and the combination of the two for predicting poor prog-nosis in elderly DN patients were 0.774,0.777,and 0.852,respectively,and the AUCs for the combination of the two were the largest(Z/P=2930/0.003,3335/0.001).Conclusion Elevated serum LncRNA Dlx6os1 levels and reduced LncRNA TUG1 levels in elderly DN patients are associated with increased risk of aggravated renal injury and poor prognosis,and serum LncRNA Dlx6os1 in combination with LncRNA TUG1 levels are of high value for predicting poor prognosis in elderly DN patients.
基金项目
陕西省重点研发计划项目(2019-YBSF-568)
维普
万方数据