Clinicopathological Features Of Multicentric IgA Nephropathy And The Role Of Elabela In IgA Nephropathy

Objective: 1.The clinicopathological data of patients with multi-center IgA Nephropathy were retrospectively analyzed and divided into three groups according to Lee classification.The clinicopathological characteristics and risk factors affecting the severity of IgA nephropathy were compared among the three groups.2.To explore the correlation between serum Elabela level and clinicopathology of IgAN patients,and to explore whether serum Elabela level is related to Lee grade and Oxford type of IgA nephropathy,so as to provide new ideas for predicting pathological damage and treatment of the disease.Methods: 1.A total of 512 patients with pathologically diagnosed IgAN who underwent renal biopsy in the Department of Nephrology of the Second Hospital of Jilin University,People’s Hospital of Jilin City and People’s Hospital of Jilin Province from October 2012 to October 2021 were collected,including general data,clinical data and pathological data.The pathological damage of IgAN patients was evaluated by Lee grading.Statistical software was used to compare the clinicopathological data of IgAN patients with different pathological grades and the risk factors affecting the severity of IgA nephropathy.2.A total of 60 patients diagnosed with IgA nephropathy by renal puncture in the Department of Nephrology,The Second Hospital of Jilin University from October 2018 to October 2021 and healthy subjects matched with age,sex and body mass index of IgAN patients were enrolled as the control group.IgA nephropathy patients were divided into two groups according to Lee grading: IgA1 group（IgA Lee I^III,28 patients）and IgA2 group（IgA Lee IV^V,32 patients）.According to Oxford classification,they were divided into M0 group（n=2）and M1 group（n=58）.E0 group（n=43）,E1 group（n=17）;S0 group（n=48）,S1 group（n=12）;T0 group（n=17）,T1 group（n=26）,T2 group（n=17）;There were fewer cases in C1 and C2 groups,so they were divided into C0 group（n=39）and C1+2 group（n=21）.Fasting venous blood of IgAN patients and healthy subjects was collected,centrifuged immediately and supernatant was taken and stored in-80℃ refrigerator.Enzyme-Linked immunosorbent assay（ELISA）was used to determine serum Elabela concentration.Statistical methods were used to analyze the relationship between serum Elabela level and clinicopathology of patients with IgA nephropathy,and to explore whether serum Elabela level was related to Lee grade and Oxford type of IgA nephropathy.Results: 1.Comparison of clinicopathological features of IgA nephropathy patients with different pathological grades（1）Comparison of basic clinical data of IgA nephropathy patients with different Lee pathological grades A total of 512 patients with IgAN were enrolled in this study,which were divided into 3 groups according to Lee classification,including IgAN1 group（IgAN Lee Grade I-II,58 patients）,IgAN2 group（IgAN Lee Grade III-IV,371 patients）and IgAN3 group（IgAN Lee Grade V,83 patients）.Different pathological grading of the patient’s age,sex,body mass index（BMI）,double leg edema,platelet count,white blood cell count,neutrophil count,fasting glucose,total protein,total cholesterol,triglycerides,high-density lipoprotein cholesterol（hdl-c）,low-density lipoprotein cholesterol（ldl-c）,urine red blood cells and urine leucocyte,high-sensitivity c-reactive protein,C3,C4 and creatine kinase,creatine kinase isoenzyme And lactate dehydrogenase had no statistical significance.With the increase of pathological grade of IgAN patients in the three groups,the levels of hemoglobin,serum albumin,e GFR,serum Ig G and serum Ig M in IgAN1 group,IgAN2 group and IgAN3 group gradually decreased,and the levels of serum creatinine,blood urea nitrogen,uric acid,SCys C,systolic blood pressure,diastolic blood pressure,24-hour urine protein and serum IgA gradually increased.The difference was statistically significant（P<0.05）.（2）Comparison of pathological data of IgA nephropathy patients with different pathological grades Katafuchi score was used for the pathological data of IgAN patients in the three groups in this study.The pathological scores of IgAN patients included spherical sclerosis score,segmental sclerosis score,glomerular mesangial cell proliferation score,renal tubular atrophy score,interstitial fibrosis score,inflammatory cell infiltration score,vascular wall thickening score and hyaline degeneration score（P<0.05）,and were positively correlated with the pathological grade of IgAN patients.In this study,the most common immunofluorescence types of IgAN patients were IgA type alone and IgA+C3 type,among which IgA+C3 type was less common in IgAN1 group than IgAN2 group and IgAN3 group,and the difference was statistically significant（P<0.05）,there was no statistical significance in the other immunofluorescence types of IgAN patients with different Lee grades（P > 0.05）（3）Analysis of risk factors for pathological grade progression in IgAN patients In this study,univariate logistic regression analysis showed that serum creatinine,blood urea nitrogen,urinary protein,uric acid,serum Ig M,e GFR,hemoglobin and neutrophils/WBC ratio were correlated with the severity of pathological grade in IgAN patients（P<0.05）.Multivariate logistic regression analysis showed that high uric acid,anemia and low e GFR were independent risk factors for pathologic progression of IgAN patients.2.Correlation between serum Elabela level and clinicopathological data of patients with IgA nephropathy.（1）Differences of serum Elabela level in patients with nephropathy of different IgAN Lee grades.In general,serum Elabela levels in IgAN patients increased with the increase of pathological grade.Serum Elabela levels were similar between the healthy control group and IgAN Lee grade I to III group without statistical difference（P>0.05）,and serum Elabela level in IgAN Lee IV^V group was significantly higher than that in healthy control group and IgAN Lee I^III group,with statistical significance（P<0.05）.（2）Comparison of Elabela levels between IgAN Oxford types.The serum Elabela level of IgAN patients in Oxford type T2 group was significantly higher than that in T0 group and T1 group,and the difference was statistically significant（P<0.05）;With the increase of interstitial fibrosis and tubule atrophy in IgAN patients,serum Elabela level gradually increased.However,there was no statistically significant difference in Elabela level among Oxford classification group E,group S and group C of IgAN patients（P > 0.05）.（3）Correlation between serum Elabela level and clinicopathological data of patients with IgA nephropathy and risk factors.Serum Elabela level was negatively correlated with hemoglobin and e GFR（P < 0.05）.There was positive correlation with serum creatinine,blood urea nitrogen,urine red blood cell,24-hour urine protein,glomerular sclerosis score,renal tubular atrophy score,interstitial fibrosis score,inflammatory cell infiltration score and Oxford type T（P < 0.05）.According to multiple linear regression analysis,the independent risk factors for serum Elabela elevation in IgAN patients were e GFR and inflammatory cell infiltration in renal pathological lesions.Conclusion: 1.Anemia,high uric acid and low e GFR are independent risk factors for the pathological progression of IgAN patients,and renal biopsy should be performed as soon as possible in clinical practice to clarify the treatment plan for such patients.2.The serum Elabela level of IgAN Lee grade IV^V patients was significantly higher than that of healthy control group and IgAN Lee grade I^II.The level of serum Elabela in Oxford type T2 group of IgAN patients was significantly higher than that in T0 group and T1 group.e GFR and inflammatory cell infiltration were independent risk factors for elevated Elabela level.