Study On The Relationship Between Serum Complement Factor,Complement Regulatory Protein And DKD

Objective:To observe the relationship between serum complement factors(Clq,C3a,C5a,MBL and MAC)and serum complement regulatory proteins(CD59,CD46)and diabetic renal disease,and to evaluate their diagnostic value in early diabetic renal disease and their predictive value in the progression of renal function.Methods:A total of 312 patients were enrolled in the second affiliated Hospital of Kunming Medical University from June 2020 to December 2020.Group A:simple diabetes;group B:diabetic kidney disease;group C:no diabetes and chronic kidney disease.(group B was divided into 30mg/g ≤UACR<300mg/g or 60ml min-1(1.73m2)-1≤eGER<90ml·min-1(1.73m2)-1 UACR B-2 groups:UACR≥ 300mg/g or eGER<60ml min-1(1.73m2)-1),five serum complement factors(Clq,C3a,C5a,MBL and MAC)and two serum complement regulatory proteins(CD59,CD46)were detected by enzyme-linked immunosorbent assay((ELISA)).Collect the clinical and laboratory data of the patients,including demographic data(such as sex,age,height,weight,primary disease)and laboratory indicators(such as serum albumin,serum creatinine,blood urea nitrogen,total cholesterol,triglyceride,serum uric acid,blood leukocytes,hemoglobin).Glomerular filtration rate was estimated by EPI formula.Statistical methods:the data were analyzed by SPSS25.0 statistical software,the clinical data and serum complements of each group were compared,the renal function indexes and serum complements were analyzed by Spearman correlation analysis,the influencing factors of early diabetic renal disease were analyzed by univariate and multivariate Logistic regression analysis,and the diagnostic value of serum complements in early diabetic renal injury was evaluated by(ROC)curve of subjects’working characteristics.The difference was statistically significant(P<0.05).Results:1.Comparison of clinical data and complements among groups A,B and CAmong the 312 patients,the average age was(54.7±15.5)years,including 176males(56.4%)and 136females(43.6%),including 125cases(40.1%)in group A,76 cases(24.4%)in group B and 111cases(35.6%)in group C.There was no significant difference in sex,platelet,leukocyte and total cholesterol among the three groups(all P>0.05).The age of patients in group B was the highest,the levels of hemoglobin,albumin,triglyceride,glomerular filtration rate and body mass index were the highest in group An and the lowest in group C,while the levels of blood urea nitrogen,serum creatinine,serum uric acid,systolic blood pressure and diastolic blood pressure were the lowest in group An and the highest in group C.The levels of complement factors Clq,C3a,C5a,MBL and MAC were the highest in group B,the level of serum complement regulatory protein CD59 was the lowest in group B,and the level of CD46 was higher in group B and C,the difference was statistically significant(P<0.05).Compared with group A and group C,the levels of complement factors Clq,C3a,C5a,MBL and MAC in group B increased significantly and CD59 decreased significantly in group B,but there was no significant difference between group A and group C.2.1.Comparison of clinical data and serum complements between group A and group B-1 and group B-2The average age of 201 patients was 58.3±18.6 years,including 117males(58.2%)and 84 females(41.8%),including 125cases in group A(62.2%),33 cases in group 1(16.4%)and 43 cases in group 2(21.4%).The levels of white blood cell,blood urea nitrogen,serum creatinine,systolic blood pressure and serum complement factors Clq,C3a,C5a,MBL and MAC increased gradually from group A to group BMII.Hemoglobin,albumin,glomerular filtration rate and the level of serum complement regulatory protein CD59 decreased,while the level of CD46 was higher in BMUI 1 and BMel 1 groups.Furthermore,the complement factors in group A were significantly higher than those in group B(P<0.05),while the level of CD59 in group B was significantly lower than that in group B(P<0.05),but there was no significant difference in CD46 between group An and group B(P>0.05).2.2.Correlation between serum complement and related indexes of renal function(Spearman correlation analysis)The results of Spearman correlation analysis showed that serum complement factors Clq,C3a,C5a,MBL and MAC were negatively correlated with hemoglobin,albumin and glomerular filtration rate,positively correlated with blood urea nitrogen,serum creatinine,serum uric acid and urinary albumin,and serum complement regulatory protein CD59 was negatively correlated with serum uric acid and urinary albumin.The results showed that serum complement regulatory protein Clq,C3a,C5a,MBL and MAC were negatively correlated with hemoglobin,albumin and glomerular filtration rate,and positively correlated with blood urea nitrogen,serum creatinine,serum uric acid and urinary albumin.There was a positive correlation between CD46 and urinary albumin,and the difference was statistically significant(all P<0.05).2.3.Analysis of influencing factors of early renal damage in patients with diabetes mellituThe significant difference between group A and group B-1(d:P<0.05)was included in the univariate logistic regression,and the multivariate Logistic regression analysis was further included in the univariate logistic regression:Serum complement factor Clq(OR=1.032,95%CI 1.016-1.049 P<0.001),MBL(OR=1.007,95%CI 1.002-1.012,P=0.012)and MAC(OR=1.01,95%CI 1.003-1.016,P=0.003)were independent risk factors for early diabetic kidney disease.Glomerular filtration rate(OR=1.032,95%CI 1.016-1.049,P<0.001)and serum complement regulatory protein CD59(OR=0.958,95%CI 0.924-0.922,P<0.017)were independent protective factors for early diabetic kidney disease.2.4.Diagnostic value of serum complement in early diabetic renal injuryThe results of ROC curve showed that the sensitivity of serum Clq,MBL,MAC and CD59 in the diagnosis of early diabetic kidney disease was 84.8%,87.9%,93.9%and 39.4%,respectively,and the specificity was 80.0%,74.4%,79.2%and 98.4%,respectively.The AUC shown by the AUC curve was 0.893,0.828,0.908 and 0.73,of which MAC had the largest AUC(0.908).Conclusions:1.Relationship between serum complement and diabetic kidney disease:There is a phenomenon of global complement activation in patients with diabetic kidney disease,and circulating complement activation occurs in early diabetic kidney disease,which is related to the degree of renal injury.2.Relationship between serum complement and renal function index in patients with diabetes mellitu:There was a strong correlation between serum complement factor and renal function index,and there was a significant correlation between serum complement factor and complement regulatory protein and urinary Microalbumin/urinary creatinine ratio.It is suggested that serum complement plays a positive role in monitoring the progress of renal function and evaluating the degree of renal injury.3.Predictive value of serum complement in early diabetic kidney disease:Serum complement factors C1q,MBL and MAC are independent risk factors for early renal injury in patients with diabetes,and serum complement regulatory protein CD59 is an independent protective factor for early renal injury in patients with diabetes.4.The value of serum complement in the diagnosis of early diabetic kidney disease:the results of ROC curve showed that the areas under the curve of serum C1q,MBL,MAC and CD59 were all more than 0.7,and the sensitivity and specificity were all high,among which the AUC of MAC was the highest,indicating that it is possible to find new therapeutic targets by regulating the complement system and then develop new drugs to interfere with diabetic renal disease.