Clinical Significance Of Immunoglobulin And Complement In Patients With Type 2 Diabetes Mellitus Combined With Nephropathy

Objective:By retrospectively analyzing the clinicopathological data of patients with type 2diabetes mellitus（T2DM）combined with nephropathy,to analyze the clinical characteristics of different pathological types and to explore the pattern of changes of immunoglobulin and complement in patients with T2 DM combined with nephropathy,and the significance of differentiation in diabetic kidney disease（DKD）and nondiabetic kidney disease（NDKD）.Methods:In this study,250 patients with T2 DM combined with nephropathy confirmed by renal puncture biopsy at the Department of Nephrology,Second Hospital of Jilin University,from September 2015 to October 2021,and 150 healthy physical examiners selected during the same period were retrospectively studied.This study was divided into three parts:（1）According to whether the disease was present or not,T2 DM combined with nephropathy group and healthy control group were divided.（2）According to the type of pathology,DKD group,NDKD group,and DKD+NDKD group were divided.On this basis,according to 24-Hour urinary protein（24h UP）,each was divided into non-nephrotic range proteinuria group（24h UP <3.5g/24h）and nephrotic range proteinuria group（24h UP ≥3.5g/24h）.（3）According to whether Ig G deposition was in kidney tissue,DKD patients were divided into Ig G positive group and Ig G negative group.General,laboratory,and pathological data of the patients were collected.SPSS 26.0 statistical software was applied for data analysis.Results:1.The T2 DM combined nephropathy group had lower serum Ig G,Ig M,C3,C4,and C1 q levels compared with the healthy control group（p<0.05）,there was no statistical difference in age,gender,and Ig A level（p>0.05）.2.Among 250 patients with T2 DM combined with nephropathy,the pathological findings of renal puncture biopsy were DKD in 83 cases（33.20%）,NDKD in 114cases（45.60%）,and DKD+NDKD in 53 cases（21.20%）.The most common type of pathology in NDKD group and DKD+NDKD group was membranous nephropathy overall.The most common pathological type in the NDKD group was membranous nephropathy,followed by Ig A nephropathy and hypertensive renal damage;the most common pathological type in the DKD+NDKD group was also membranous nephropathy,followed by hypertensive renal damage and hepatitis B virus-associated glomerulonephritis.3.Analysis of clinical data of DKD group,NDKD group,and DKD+NDKD groupAnalysis of general data: The DKD group had lower age,longer duration of diabetes mellitus（DM）,higher systolic and diastolic blood pressure,and higher proportion of hypertension and diabetic retinopathy（DR）compared with the NDKD group（p<0.05）.The DKD group had lower age compared with the DKD+NDKD group（p<0.05）.The DKD+NDKD group had longer duration of DM and higher proportion of DR compared with the NDKD group（p<0.05）.There was no statistical difference among the three groups in terms of gender,body mass index（BMI）,smoking history,and alcohol-drinking history（p>0.05）.Analysis of laboratory data: The DKD group had lower hemoglobin,albumin,triglyceride,and estimated glomerular filtration rate（e GFR）levels,higher homocysteine（Hcy）,blood urea nitrogen（BUN）,serum creatinine（Scr）,24 h UP levels and mean value of the longitudinal axis of both kidneys,and higher proportion of renal insufficiency and hematuria compared with the NDKD group（p<0.05）.The DKD group had lower hemoglobin and e GFR levels,higher Hcy,BUN,and Scr levels,and higher proportion of renal insufficiency compared with the DKD+NDKD group（p<0.05）.The DKD+NDKD group had lower hemoglobin level and higher mean value of the longitudinal axis of both kidneys compared with the NDKD group（p<0.05）.There was no statistical difference among the three groups in the remaining indicators（p>0.05）.Analysis of serum immunoglobulin and complement data: The DKD group had lower C3 level compared with the NDKD group（p < 0.05）,the DKD+NDKD group had lower C3 level compared with the NDKD group（p<0.05）,there was no statistical difference among the three groups in Ig G,Ig A,Ig M,C4,and C1q（p > 0.05）.In the non-nephrotic range proteinuria group,there was no statistical difference among the three groups in terms of Ig G,Ig A,Ig M,C3,C4,and C1q（p>0.05）.In the nephrotic range proteinuria group,the DKD group had higher Ig G level and lower C3 level compared with the NDKD group（p<0.05）,the DKD+NDKD group had lower C3 level compared with the NDKD group（p<0.05）,there was no statistical difference among the three groups in Ig A,Ig M,C4,and C1q（p>0.05）.In the DKD group,the nephrotic range proteinuria group had lower Ig G level and higher C1 q level compared with the non-nephrotic range proteinuria group（p<0.05）,there was no statistical difference in Ig A,Ig M,C3,and C4（p>0.05）.In the NDKD group,the nephrotic range proteinuria group had lower Ig G level and higher C3,C4,and C1 q levels compared with the non-nephrotic range proteinuria group（p<0.05）,there was no statistical difference in Ig A and Ig M（p>0.05）.In the DKD+NDKD group,there was no statistical difference between the nephrotic range proteinuria group and the non-nephrotic range proteinuria group in terms of Ig G,Ig A,Ig M,C3,C4,and C1q（p>0.05）.4.Analysis of risk factors for the development of NDKD in patients with T2 DM combined with nephropathy: By univariate logistic regression analysis,the significant variables were screened,including age,BMI,duration of DM,history of hypertension,DR,serum C3,hemoglobin,albumin,triglycerides,BUN,Scr,e GFR,24 h UP,and mean value of the longitudinal axis of both kidneys.Further incorporation of multivariate logistic regression analysis showed that advanced age,shorter duration of DM,non-combined DR,high serum C3,and high hemoglobin levels were independent risk factors for the development of NDKD in patients with T2 DM combined with nephropathy.The ROC curve was applied to evaluate the predictive value of C3 in the development of NDKD in patients with T2 DM combined with nephropathy,the area under the ROC curve for C3 was 0.678,the cut-off value was93.70（mg/d L）,the sensitivity was 57.0%,and the specificity was 71.1%.5.In DKD patients,the Ig G positive group had higher BMI,lipoprotein（a）,urinary microalbumin,and urinary red blood cell levels compared with the Ig G negative group（p<0.05）.There was no statistical difference between the two groups in the remaining indicators（p>0.05）.Conclusions:1.Serum immunoglobulin and complement levels were reduced in the T2 DM combined nephropathy group compared with the healthy control group.2.NDKD accounted for a large proportion of patients with T2 DM combined with nephropathy,and membranous nephropathy was the most common pathological type of NDKD.Advanced age,shorter duration of DM,non-combined DR,high serum C3,and high hemoglobin levels were independent risk factors for the development of NDKD in patients with T2 DM combined with nephropathy.For patients with clinical features of NDKD,aggressive renal puncture biopsy is recommended to clarify the pathological type.3.Patients with DKD accompanied by Ig G deposition in kidney tissue had more severe kidney damage.