Expression And Clinical Value Of Serum HMGB1 And NLRP3 In Diabetic Kidney Disease

Objective:To investigate the expression of high mobility group protein 1（HMGB1）and NOD-like receptor thermal protein domain associated protein 3（NLRP3）in patients with diabetic kidney disease（DKD）and to analysis their clinical value in the progression of chronic kidney disease（CKD）.Methods:122 type 2 diabetes mellitus（T2DM）patients who were hospitalized in the second Hospital of Lanzhou University from January 2021 to December 2021 and40 healthy adults of the same age at the medical examination center were included.The basic information of age,sex,height,weight,systolic blood pressure（SBP）,diastolic blood pressure（DBP）and the course of diabetes were collected,the related indexes of glucose metabolism,blood lipid,renal function and electrolytes were collected,24-hour urine protein（24h-UP）,urine protein,urine creatinine,albumin（ALB）,and 25hydroxyvitamin D（25（OH）D）were collected.Body mass index（BMI）,urinary albumin to creatinine ratio（UACR）,urinary albumin excretion rate（UAER）and estimated glomerular filtration rate（e GFR）were calculated.In term of the 2021 edition of Chinese guidelines for the prevention and treatment of diabetic kidney disease,the122 patients were grouped in three ways:（1）It is fell into three groups in term of the severity of UACR:normal albuminuria group（group D1,n=45）,microalbuminuria group（group D2,n=31）and macroalbuminuria group（group D3,n=46）.（2）It is fell into two groups in term of the degree of e GFR level:e GFR≥60m L/min/1.73m~2 group（E1 group,n=79）and e GFR<60m L/min/1.73m~2 group（E2 group,n=43）.（3）It is fell into three groups in term of the risk of CKD progression according to e GFR and UACR classification:low risk group（group F1,n=46）,medium and high risk group（group F2,n=39）and very high risk group（group F3,n=37）.And 40 healthy individuals as negative control group（NC group）.The content of serum HMGB1 and NLRP3 were tested by enzyme linked immunosorbent assay（ELISA）.The outcome and relevant clinical indexes were statistically analyzed by SPSS 25.0,P<0.05 refers to statistical implication.Results:1.In groupings based on the severity of the UACR,the HMGB1 and NLRP3 in D1,D2 and D3 groups were higher than those in NC group,the difference is prominent（P<0.05）.The HMGB1 in D2 and D3 group was higher than that in D1group（P<0.05）,but there was no remarkable distinction between D3 group and D2group（P>0.05）.The NLRP3 in D2 and D3 group was higher than that in D1 group,and that in D3 group was higher than that in D2 group（P<0.05）.There was a prominent positive correlation between UACR with HMGB1 and NLRP3（P<0.001）.Multivariate ordered Logit regression showed that elevated NLRP3 level（OR=1.08,95%CI:1.040?1.120）was a separate risk factor for increased albuminuria in patients with DKD.Binary logistic regression showed that NLRP3（OR=1.157,95%CI:1.078?1.240）was separate risk factor for DKD patients with UACR≥30mg/g.The area under the ROC curve of DKD patients with UACR≥30mg/g evaluated by NLRP3 was 0.879.2.In groupings based on the level of the e GFR,compared with NC group,HMGB1and NLRP3 in E1 and E2 groups increased,E2 group was higher than E1 group,there were prominent differences among the three groups（P<0.05）,e GFR has prominent negative correlation with HMGB1 and NLRP3（P<0.001）.Binary logistic regression showed that elevated NLRP3 level（OR=1.070,95%CI:1.017?1.125）was separate risk factor for DKD patients with e GFR<60m L/min/1.73m~2.The area under the ROC curve of DKD patients with e GFR<60m L/min/1.73m~2 evaluated by NLRP3 was 0.858.3.In groupings based on the risk of CKD progression,the HMGB1 and NLRP3 of F1,F2 and F3 groups were higher than those of NC group,and the HMGB1 of F2 and F3 group was higher than that of F1 group（P<0.05）,but there was no remarkable distinction between F3 group and F2 group（P>0.05）.The NLRP3 of F2 and F3 group was higher than that of F1 group,and that of F3 group was higher than that of F2 group（P<0.05）.Multivariate ordered Logit regression showed that elevated HMGB1 level（OR=1.002,95%CI:1.001?1.003）was the separate risk factor for the severity of CKD progression risk in DKD patients.Binary logistic regression showed that elevated NLRP3 level（OR=1.054,95%CI:1.011?1.099）was separate risk factor for very high risk progression of CKD.The areas under the ROC curves of NLRP3 at very high risk of CKD progression was 0.852.Multivariate linear regression indicated that Scr（β=1.455,P<0.05）and SUA（β=1.851,P<0.05）were positive influencing factors of HMGB1.Scr（β=0.02,P<0.05）and SBP（β=0.169,P<0.05）were positive influencing factors of NLRP3.e GFR（β=-0.175,P<0.05）and ALB（β=-0.465,P<0.05）were negative factors for NLRP3.Conclusion:1.The levels of serum HMGB1 and NLRP3 in patients with DKD are higher than those in normal subjects,which is closely related to the severity of DKD（increase in albuminuria and decrease in e GFR）.2.Both HMGB1 and NLRP3 are associated with CKD progression in patients with DKD,they may provide reference for the prediction of early diagnosis and disease progression of DKD.