Risk Factors For Progression Of IgA Nephropathy And Comparison Of Different Regimens In IgA Nephropathy

[Background] Primary IgA nephropathy is a common nephritis manifesting as hematuria,proteinuria,renal dysfunction or hypertension,and some patients will eventually progress to end-stage renal disease(ESRD).At present,independent risk factors for IgA nephropathy to ESRD may include proteinuria,hypertension,renal insufficiency,hyperuricemia and so on,and the relationship between parameters such as serum phosphate or PTH and disease prognosis is unclear.There are various kinds of treatment for IgA nephropathy patients,which includes ACEI / ARB,steroids and immunosuppressive agents.The KDIGO guideline suggests that steroids should be used in patients with persistant proteinuria>1.0 g / d of after supportive therapy,while the use of immunosuppressive agents is complicate.There is still no consensus on the treatment of IgA nephropathy patients with varying levels of proteinuria.Renal interstitial fibrosis is one of the common pathways for the progression of chronic kidney disease to ESRD.Previous studies have suggested that PTH may play an important role in the pathogenesis of renal interstitial fibrosis,whereas the relationship between serum PTH and renal interstitial fibrosis levels is to be further studied.[Objects] to investigate risk factors of IgA nephropathy progression,and to compare different regimens in the treatment of IgA nephropathy.[Methods] This was a retrospective study.Clinical parameters of IgA nephropathy patients of different oucome were collected and compared respectively through univariate analysis.Multivairate COX regression model was built up to find out independent risk factos for disease progression.Patients were divided into three groups according to different regimens including ACEI/ARB,ACEI/ARB combined with steroids as well as steroids combined with immunosuppressive agents.Stratified analysis based on proteinuria was conducted to compare the efficacy of those regimens on different proteinuria levels.Correlation between renal interstitial fibrosis levels and serum i PTH levels was studied and multivariate linear regression model was proposed to predict renal fibrosis levels.[Results] 1628 IgAN patients were enrolled in the first part of the study,including 835 males and 793 females.The average age was 36±12 years old.Univariate analysis indicated that baseline blood pressure,24 h proteinuria,serum uric acid,triglyceride,total cholesterol and serum phosphate were significantly higher in patients eventually progressed to ESRD compared to those didn’t progress to ESRD.While hemoglobin,serum albumin,e GFR and serum calcium levels were significantly lower(P<0.01).COX regression model reveals that male(P=0.027,OR=0.558),hypertension(P=0.001,OR=2.508),hypoalbuminemia(P=0.014,OR=0.953),lower baseline e GFR(P<0.001,OR=0.942),higher serum phosphate(P=0.016,OR=3.071),higher serum i PTH(P=0.002,OR=1.006)are independent risk factors for IgA nephropathy progression to ESRD.410 IgAN patients were enrolled in the second part of the study to compare different regimens in IgAN,which included 204 males and 206 females,the average age was 36±12 years old.ANOVA and Kaplan-Meier Survival Curve indicated that patients in the ACEI/ARB group and in the steroids group acquired better long-term outcome when initial proteinuria was less than 1.0g/d.Patients in ACEI/ARB group acquire best long-term outcome when initial proteinuria is 1.0-3.5g/d.And patients in immunosuppressive group acquire better long-term outcome when initial proteinuria is more than 3.5g/d.Proteinuria significantly decreased in almost every regimen group in each stratified analysis(P<0.05).226 IgAN patients were enrolled in the third part of the study to investigate the correlation between renal interstitial fibrosis and serum i PTH levels in IgAN,including 109 males and 117 females,the average age of which was 38±12 years old.ANOVA indicates that i PTH with different renal interstitial fibrosis levels are of significant difference(P<0.01).Spearman correlation analysis indicates that serum i PTH correlates with renal fibrosis levels significantly(P<0.01,R=0.35).Multivariate linear regression indicates that age of onset,serum i PTH and initial e GFR could reflect the severity of renal interstitial fibrosis.[Conclusions] Male,hypertension,hypoalbuminemia,low baseline e GFR,high serum phosphate and high serum PTH levels are independent risk factors for the progression of IgA nephropathy.For IgAN patients with mild proteinuria,ACEI / ARB combined with steroids were effective in reducing proteinuria,and ACEI/ARB was effective in protecting renal function,with or without steroids.For patients with moderate proteinuria,all the three regimens were effective in reducing proteinuria while ACEI/ARB alone was more beneficial in protecting long-term renal function.And for patients with severe proteinuria,the use of steroids combined with immunosuppressive agents(CTX / CNI / MMF)was more effective and could significantly improve proteinuria and the long-term prognosis was also better.Serum PTH correlates with levels of renal interstitial fibrosis.Serum PTH is an independent factor in predicting renal interstitial fibrosis levels in IgA nephropathy.