Relationships of soluble triggering receptor expressed on myeloid cell-1 and tissue inhibitor of metalloproteinase 3 levels with the severity and prognosis of diabetic nephropathy
Objective To observe the changes of serum soluble triggering receptor expressed on myeloid cell-1(sTREM-1)and tissue inhibitor of metalloproteinase 3(TIMP3)levels in patients with diabetic nephropathy(DN),and to investigate their relationships with the disease severity and prognosis of DN patients.Methods From January 2018 to December 2020,130 DN patients(DN group),80 type 2 diabetes mellitus(T2DM)patients(T2DM group),and 80 healthy controls(control group)in the First Affiliated Hospital of Xi'an Jiaotong University were detected the serum sTREM-1 and TIMP3 levels using ELISA.Based on estimated glomerular filtration rate(eGFR),DN patients were categorized into G1[eGFR:≥90 mL/(min·1.73 m2),n=31],G2[eGFR:60 to＜90 mL/(min·1.73 m2),n=18],G3[eGFR:30 to＜60 mL/(min·1.73 m2),n=25],and G4[eGFR:15 to＜30 mL/(min·1.73 m2),n=56]stages.The serum sTREM-1 and TIMP3 levels were compared among DN,T2DM and control groups,and across G1 to G4 stages.DN patients were divided into poor prognosis group(n=39)and good prognosis group(n=91)based on the three-year follow-up results,and the clinical data as age and serum sTREM-1 and TIMP3 levels were compared between two groups.The correlations of eGFR with serum sTREM-1 and TIMP3 levels were analyzed using Spearman's method.Multivariate Cox regression was used to analyze the influencing factors of poor prognosis of DN patients.ROC curves were plotted to evaluate the efficiencies of serum sTREM-1 and TIMP3 levels on predicting poor prognosis of DN patients.Results Significant differences were found in serum sTREM-1[(71.45±19.34),(101.24±24.83),(138.21±33.68)ng/L]and TIMP3 levels[(968.99±187.77),(862.21±202.93),(671.55±160.55)ng/L]among control,T2DM and DN groups(F=146.005,P＜0.001;F=72.384,P＜0.001),with serum sTREM-1 levels increasing(P＜0.05),and TIMP3 levels decreasing sequentially(P＜0.05).Significant differences were also observed in serum sTREM-1[(94.41±16.93),(125.59±14.71),(138.62±11.68),(166.33±20.95)ng/L]and TIMP3 levels[(858.87±81.85),(765.05±64.48),(696.16±30.38),(526.82±103.85)ng/L]from G1to G4 stages(F=112.836,P＜0.001;F=114.064,P＜0.001),with sTREM-1 levels increasing(P＜0.05),and TIMP3 levels decreasing sequentially(P＜0.05).The eGFR was positively correlated with serum sTREM-1 level(r=0.787,P＜0.001),and was negatively correlated with TIMP3 level in DN patients(r=-0.796,P＜0.001).At a follow-up of(2.53±0.36)years,the poor prognosis rate was 30.00％in 130 DN patients.The age was older in poor prognosis group[(62.62±11.11)years]than in good prognosis group[(58.20±11.40)years](t=2.039,P=0.043).The rate of hypertension,and the levels of glycosylated hemoglobin,blood uric acid,blood creatinine and sTREM-1 were higher in poor prognosis group[35.90％,8.07％(7.37％,9.48％),(393.23±66.97)mmol/L,185.76(158.48,212.46)μmol/L,(163.12±27.16)ng/L]than those in good prognosis group[13.19％,7.43％(6.68％,8.41％),(358.11±80.68)mmol/L,159.12(133.67,189.54)μmol/L,(127.54±30.50)ng/L](x2=8.800,U=3.480,t=2.388,U=2.949,t=6.293;all P values＜0.05),while the eGFR and the levels of albumin and TIMP3 were lower in poor prognosis group[21.80(17.13,39.62)mL/(min·1.73 m2),(31.62±7.05)g/L,(550.49±155.35)ng/L]than those in good prognosis group[60.36(23.36,95.46)mL/(min·1.73 m2),(34.41±5.19)g/L,(723.44±133.14)ng/L](U=5.108,P＜0.001;t=2.227,P=0.030;t=6.450,P＜0.001).Hypertension(HR=3.587,95％CI:1.110-11.589,P=0.033),glycosylated hemoglobin(HR=2.801,95％CI:1.383-5.671,P=0.004),eGFR(HR=0.956,95％CI:0.928-0.985,P=0.003),sTREM-1(HR=1.047,95％CI:1.020-1.074,P=0.001),and TIMP3(HR=0.992,95％CI:0.987-0.996,P=0.001)were the influencing factors of poor prognosis of DN patients.When using the cut-off values of serum sTREM-1 and TIMP3 of 132.67 and 606.51 ng/L,the AUCs of serum sTREM-1,TIMP3,and their combination for predicting poor prognosis of DN patients were 0.793(95％CI:0.713-0.859,P＜0.001),0.796(95％CI:0.717-0.862,P＜0.001),and 0.875(95％CI:0.806-0.927,P＜0.001),with the sensitivities of 89.74％,66.67％and 79.49％,and the specificities of 53.85％,81.32％and 87.91％,respectively.The AUC of their combination was greater than that of sTREM-1 and TIMP3 alone(Z=2.767,P=0.007;Z=2.763,P=0.006).Conclusions With the aggravation of disease severity,the serum sTREM-1 level increases and the TIMP 3 level decreases in DN patients.Those with hypertension,elevated levels of sTREM-1 and glycosylated hemoglobin,and reduced eGFR and TIMP3 level have a high risk of poor prognosis,and the combined detection of serum sTREM-1 and TIMP3 levels has a high value to the prediction of poor prognosis of DN patients.
diabetic nephropathysoluble triggering receptor expressed on myeloid cell-1tissue inhibitor of metalloproteinase 3severity of disease
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