Correlation Between M2 Macrophages,AIM,TGFβ1 And Renal Fibrosis In IgA Nephropathy

Background: IgA(IgA nephropathy,IgAN)as a common primary glomerular disease in China,is one of the main causes of glomerulosclerosis,tubular matrix fibrosis and endstage renal disease.Renal fibrosis is the common way for all CKD(Chronic kidney disease)to progress and eventually to ESRD(end-stage kidney disease).How to slow down renal fibrosis is one of the most important links in the treatment of CKD.At present,many studies have found that macrophages,AIM(Apoptosis inhibitor of macrophage)and TGF-beta 1(transforming growth factor-β1)play an important role in this process,which will also provide new ideas for the study and treatment of renal fibrosis.Purpose: To observe the infiltration of M2 macrophages,the expression of AIM and TGF-beta 1 in the tissues of IgAN patients,and to explore the characteristics of M2 macrophage infiltration,the expression of AIM and TGF-beta 1 in the kidney tissues of IgAN,and the relationship between them and serum creatinine,24-hour urinary protein,e GFR and the area of renal fibrosis in IgAN.Methods: Thirty-nine patients with IgA nephropathy were selected from November 2017 to August 2018 in the Department of Nephrology of SUBEI’s Hospital(all specimens were diagnosed as IgA nephropathy by renal biopsy light microscopy and immunofluorescence pathology,and the possibility of secondary factors such as allergic purpura,systemic lupus erythematosus and liver disease was excluded.No hormones or immunosuppressive agents were used in all patients recently).There were 19 males and 20 females,aged 23-68 years.According to the diagnostic criteria of pathological grade of IgA nephropathy in 1982,all patients were divided into grade III-V(no specimens were collected for pathological grading I-II).In the control group,5 patients with renal tumors at the same time were selected as normal kidney tissues which were more than 2cm away from the pathological changes after resection of the tumors.Immunohistochemical technique was used to detect the expression of CD163(the specific antibody of M2 macrophages in renal biopsy specimens),AIM and TGF-beta-1.To analyze the relationship between the infiltration of M2 macrophages,the expression of AIM,TGF-beta 1 and the degree of fibrosis in IgA nephropathy and the results of laboratory tests.Result:1、The infiltration of M2 macrophages and the expression of AIM,TGF-beta 1 in normal kidney and IgAN patientsThere were no(or occasional)M2 macrophages,AIM and TGF-beta 1 in normal kidney tissues,but the expressions of M2 macrophages,AIM and TGF-beta 1 in renal tissues of IgAN patients were significantly increased.There were significant differences between patients with IgA nephropathy and normal kidney group(P<0.01).In IgA nephropathy group,M2 macrophages,AIM and TGF-beta 1 increased with increasing of pathological grade,and there was significant difference between groups(P<0.01).There was a significant positive correlation between the expression of M2 macrophages,AIM and TGF-beta 1 in IgAN patients(P<0.01).2、The relationship between M2 macrophages,AIM,TGF-beta 1 and clinical data and laboratory results in patients with IgA nephropathyThere were no significant differences in age,gender,urinary erythrocyte count and NAG among different pathological groups.Among different pathological groups,24-hour urinary protein and serum creatinine increased with the increase of pathological grading,while e GFR decreased with the increase of pathological grading,and there were statistical differences between groups(P<0.01).24-hour urinary protein,serum creatinine,NAG and e GFR were significantly correlated with M2 macrophages,AIM and TGF-beta-1.24-hour urinary protein,serum creatinine,NAG were positively correlated with M2macrophages,AIM and TGF-beta-1(P<0.01),while e GFR was negatively correlated with M2 macrophages,AIM and TGF-beta-1(P<0.01).3、The relationship between the M2 macrophages,AIM,TGF-beta 1 and fibrosis area in IgA nephropathy.The area of renal fibrosis in IgAN patients was significantly increased compared with that in normal kidney tissues.The degree of renal fibrosis in IgAN patients was more obvious with the increase of pathological grade(H = 35.27,P < 0.01).There was a positive correlation between M2 macrophages and fibrosis area(r = 0.777,P < 0.01),AIM and fibrosis area(r = 0.768,P < 0.01),also TGF-beta 1 and fibrosis area(r = 0.853,P < 0.01).Conclusion:1.M2 macrophages,AIM and TGF-beta 1 were positively correlated with the degree of IgAN renal fibrosis.2.M2 macrophages may play a role in the fibrosis process of IgA nephropathy through the pathway of AIM /TGF-beta 1.