Correlation Between Urinary NLRP3 Inflammasome Pathway And Dabetic Kidney Disease

Objective:Diabetes kidney disease(DKD)is the main chronic complication of diabetes.It is easy to progress to end-stage renal disease and needs dialysis treatment.The mortality is high.Our previous basic research shows that the inflammatory body pathway of nod like receptor thermal protein domain associated protein 3(NLRP3)may be involved in the occurrence and development of DKD,but there is no research report on the changes of this pathway in patients with DKD.In this study,we observed the changes of main factors of urinary NLRP3 inflammatory body pathway in patients with type 2 diabetes and DKD,including NLRP3,apoptosis associated speck like protein containing a card(ASC),caspase-1,IL-18 and IL-1β.On the basis of previous studies,to explore the possible relationship between NLRP3 inflammatory body pathway and DKD progression.Methods:1.Patients with type 2 diabetes and DKD hospitalized in the endocrinology department from November 2021 to February 2022 were selected as the control group.2.According to the diagnostic and screening criteria of the Chinese guidelines for the prevention and treatment of diabetes kidney disease in 2021,the patients were divided into three groups according to the urinary albumin/creatinine ratio(ACR),which were normal albuminuria group(ACR<30mg/g,DM group),microalbuminuria group(30mg/g ≤ ACR<300mg/g,DN1 group),massive albuminuria group(ACR ≥300mg/g,DN2 group),and healthy adults as the control group(NC group).There are10 people in each group,a total of 40 people.3.Collect the general clinical data of patients,and detect the biochemical indexes of all subjects on an empty stomach,such as fasting blood glucose,uric acid,creatinine,etc;All subjects took 24-hour urine,measured urine volume,and measured urinary biochemical indexes,such as urinary protein,urinary creatinine,etc;Take 10 ml of urine from sterile tube for 24 hours,and detect the concentration levels of NLRP3,ASC,caspase-1,IL-18 and IL-1β by enzyme-linked immunosorbent assay(ELISA).4.Apply spss23 statistical software was used to compare the differences of general data,blood and urine biochemical indexes,and the levels of five factors of urinary NLRP3 inflammatory body pathway among the groups.The correlation between the levels of five factors of urinary NLRP3 inflammatory body pathway and various indexes was analyzed.P<0.05 was statistically significant.Results:1.There was no significant difference in age,body mass index and diastolic blood pressure among the four groups(P>0.05).There was no significant difference in the proportion of main hypoglycemic drugs and antihypertensive drugs among DM,DN1 and DN2 groups(P>0.05).2.Comparison of general blood and urine biochemical indexes:1)Compared with NC group,fasting blood glucose,creatinine,blood uric acid,blood urea nitrogen and Cystatin-C increased and albumin decreased in DN2 group(P<0.05);Compared with DM group,there were significant differences in uric acid,blood urea nitrogen,creatinine and Cystatin-C between DN1 group and DN2 group(P<0.05);There was no significant difference in uric acid,blood urea nitrogen,creatinine and Cystatin-C between DN1 group and DN2 group(P>0.05).2)There was no significant difference in fasting blood glucose,albumin,glycosylated hemoglobin and high density lipoprotein cholesterol among DM,DN1 and DN2 groups(P>0.05).3)There was no significant difference in triglyceride,total cholesterol and lowdensity lipoprotein cholesterol among the groups(P>0.05).4)The level of urinary protein in DN2 group was significantly higher than that in the other three groups(P<0.05),and there was no significant difference among other groups(P>0.05)3.Comparison of urinary NLRP3 inflammatory body factor levels:1)Compared with NC group,the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 in urine of DN2 group were significantly higher(P<0.05);The levels of IL-1β in DN1 group and ASC in DM group increased significantly(P<0.05).2)Compared with DM group,the levels of NLRP3,IL-18 and IL-1β in urine of DN2 group were significantly higher(P<0.05);There was no significant difference in five factors in DN1 group(P>0.05).3)Compared with DN1 group,the levels of five urinary factors in DN2 group increased,but did not reach significant significance(P>0.05).4)There was no significant difference in urinary caspase-1 and ASC levels among DM,DN1 and DN2 groups(P>0.05).4.Correlation between urinary NLRP3 inflammatory body factor level and other indicators:The data of DM,DN1 and DN2 groups were combined for correlation analysis,which showed that:1)Urinary IL-1β was positively correlated with ACR(r=0.375,P=0.041<0.05),while urinary NLRP3,caspase-1,ASC and IL-18 were not correlated with ACR(P>0.05).2)Urinary NLRP3 was positively correlated with serum uric acid(r=0.419,P<0.05),but not with other indexes.3)Urinary caspase-1 and age,urinary creatinine,urinary α1-microglobulin was positively correlated(The r values were 0.41,0.363 and 0.411 respectively P<0.05),and had no correlation with other indexes.4)There was no correlation between urinary NLRP3,ASC,caspase-1,IL-18 and IL-1β and serum creatinine(P>0.05).Conclusions:1.With the increase of urinary albumin level,the main factors of urinary NLRP3 inflammatory body pathway in patients with type 2 diabetes increased significantly.It is suggested that this pathway may be involved in the progression of DKD and may also be a new therapeutic target.The main factor level of urinary NLRP3 inflammatory body pathway is not affected by renal function,which can be used as a stable index to evaluate the relationship between this pathway and DKD.