The Relationship Between HE4 Tissue Expression Concentration In Renal Biopsy And Renal Interstitial Fibrosis And Prognosis In Patients With IgA Nephropathy

Objective: It is well known that IgA nephropathy is a chronic progressive kidney disease,The degree of renal interstitial fibrosis plays an important role in the progression of IgA nephropathy.HE4((Human epididymis protein 4,HE4)),as a novel biomarker of renal fibrosis,that previous studies were limited to serological levels and there were few studies on the expression concentration of HE4 in human kidney tissue.This study was performed by immunohistochemical staining of paraffin embedded pathological tissues in patients with IgA nephropathy and to analyze the changes about HE4 tissue expression concentration in renal biopsy with the progression of renal interstitial fibrosis.The objective of this study is to investigate the relationship between HE4 tissue expression concentration in renal biopsy and renal interstitial fibrosis and prognosis in patients with IgA Nephropathy.Methods:A total of 102 patients with primary IgA nephropathy who was hospitalized in our department of Nephrology form 2012-2016 were enrolled.We retrospectively collect the patient's clinical and pathological data.The acquisition of clinical data comes from our electronic medical record system.All slides were re-assessed and the grades of renal interstitial fibrosis were recorded.HE4 tissue expression concentrations in renal biopsy were assessed by immunohistochemistry,The correlation between clinical and pathological data with HE4 tissue expression concentration was analyzed.The primary end point is doubling serum creatinine,or a 50% reduction in estimated glomerular filtration rate(eGFR),or end-stage renal disease.The comparison between groups was performed by one-way ANOVA,and the correlation analysis was performed by Spearman method.The Kapla-Meier(KM)survival curve was used to assess renal survival duration,and the difference between the curves was analyzed by Log-rank.Results: 1.HE4 tissue expression concentrations were significantly increased along with severity of RIF.HE4 tissue expression concentrations in different RIF groups is of great difference by ANOVA(P<0.001).There were significant differences in 24-hour urine protein quantitation,hemoglobin,serum phosphorus,serum uric acid,serum creatinine,urea nitrogen,and glomerular filtration rate between different renal interstitial fiber grades(P<0.001).There were significant differences in MAP,24-hour urine protein quantitation,hemoglobin,serum phosphorus,serum creatinine,urea nitrogen,glomerular filtration rate,and the degree of RIF between different HE4 grades(P<0.001).Paired comparison of ANOVA among HE4 0/1+,HE4 2+ and HE4 3+ demonstrated significant difference in RIF grades(Thamane)(all the P values less than 0.01).2.Spearman analysis showed positive correlation between severity of RIF and HE4 grades(P<0.001,R=0.819).HE4 tissue expression concentration was listed in the final linear regression model to predict severity of RIF.Spearman correlation analysis showed that HE4 grade was positively correlated with 24 h urine protein(R=0.439,P<0.001);positively correlated with serum creatinine(R=0.766,P<0.001);positively correlated with urea nitrogen(R=0.654,P < 0.001);negatively correlated with eGFR(R =-0.781,P < 0.001).3.Totally 102 patients of IgA nephropathy were enrolled in the study.During the follow-up(median:50months;range:12-63 months),7.84% of the patients reached the end point.Kaplan-Meier survival curves showed that higher HE4 tissue expression concentrations were associated with shorter survival duration.Conclusion: 1.There is a strong positive correlation between RIF grades and HE4 tissue expression concentration with IgA nephropathy.HE4 tissue expression concentration is significantly higher in patients with more severe RIF lesions.2.Higher HE4 tissue expression concentrations were associated with shorter survival duration.