A Study Of Early Prognosis Model Of IgA Nephropathy

Background: Primary IgA nephropathy(IgAN)is a most common primary glomerulonephritis characterized by deposition of immunoglobulin A(IgA)in the glomerular mesangial region,with or without C3 deposition.Its pathogenesis has not yet been fully elucidated.It is considered that multifactors involved the causes of IgAN,such as autoimmunity,inflammatory activation,genetic and environmental factors.Approximately one third of IgAN patients developed into end stage renal disease(ESRD)in a 20-to 30-year period.Currently,several clinical factors,such as urinary protein,serum creatinine levels and features of renal biopsy pathology,were recognized as predictors of poor renal outcome in patients with IgAN.However,early prognosis of poor renal outcome is still difficult.How to determine who eventually will be in progress to end-stage renal disease has been the focus of clinical practice.An easily obtained clinical test which can early efficiently and accurately predict the poor renal outcome in patients with IgAN may be useful for clinician to indicate the treatment of patients with IgAN.Part I.Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with Immunoglobulin A nephropathyObject: An association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy(IgAN)remains controversial.To analyze the relationship between serum complement C3,C4 and prognosis in IgA nephropathy.Methods: We conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN.Between 2009 and 2013,patients with biopsy-confirmed IgAN were identified and various parameters were documented during follow-up until 2015.The data was analyzed using R statistical software.Results: A total of 403 patients(55.3% female,average 33.7 months of follow-up)were identified and enrolled,with the primary endpoint occurring in 39(9.8%)patients.Among the patients selected,202(50.1%)received corticosteroid treatment alone or in combination with another immunosuppressant(GS group),while others did not receive immunosuppressive treatment(non-GS group).The incidence of the primary endpoint was slightly lower in the GS group compared to the non-GS group(7.0% versus 12.6%,p = 0.06).Multivariate Cox proportional-hazard regression analyses,adjusting for age,systolic and diastolic blood pressure,24-hour urine protein,and immunosuppressive therapy,showed that serum complement 4(C4)levels(hazard ratio [HR] 2.4,95% confidence interval [CI] 1.6-3.8,p < 0.001)and serum complement 3 levels(HR 0.6,95% CI 0.2-0.6,p < 0.001)were significantly associated with a poor prognosis among patients with IgAN.For visualization of the role of these risk factors in predicting poor renal outcomes,all variables in the multivariate models were used to construct a nomogram for estimating three-and five-year survival.ConclusionsWe demonstrated that an increase in serum C4,as well as a decrease in C3,was an important outcome determinant for patients with IgAN.Testing serum C3 and C4 levels might assist in predicting renal outcomes among these patients.Using nomogram to evaluate the prognosis of IgA nephropathy was more operable and practical than commonly used clinical indicators such as urinary protein and blood creatinine.Part II.Elevated serum fibrinogen levels are an independent risk factor for IgA nephropathyObject: IgA nephropathy is a primary cause of renal failure,and inflammation and renal fibrosis are the main mechanisms leading to kidney damage.The serum fibrinogen level is closely related to inflammatory states,but its relationship to the prognosis of IgAN is unclear.To analyze the relationship between serum complement C3,C4 and prognosis in IgA nephropathy.Methods: 1053 patients diagnosed with IgAN after renal biopsy were enrolled.Demographic and clinical data and histopathological features were collected.The patients were divided into four groups(Q1-Q4)according to the serum fibrinogen levels at the time of renal biopsy,and the relationships of serum fibrinogen levels with other risk factors and the prognosis of IgAN were investigated.The data was analyzed using R statistical software.Results: 672 patients with proven primary IgAN were enrolled in this study,which included a median follow-up of 36 months.Patients with higher serum fibrinogen levels had elevated Age,body mass index,total cholesterol,triglycerides,low density lipoprotein cholesterol,serum uric acid,serum creatinine levels,24-hour urinary protein,and blood pressure compared with patients with the lowest levels of serum fibrinogen as well as severe renal damage,lower albumin and estimated glomerular filtration rate(eGFR)at the time of renal biopsy.Multivariate Cox regression analyses confirmed that the serum fibrinogen level,serum uric acid,albumin,urinary protein and T2(Renal pathology according to the Oxford classification)at the time of renal biopsy was significantly related to the prognosis of patients with IgAN.Glucocorticoid and Angiotensin-Converting Enzyme Inhibitors(ACEIs)/ angiotensin receptor blockers(ARBs)can improve the prognosis of IgA nephropathy especially in patients with high fibrinogen levels.Conclusions: In patients with IgAN,an elevated serum fibrinogen level at the time of renal biopsy is associated with poor renal outcomes,which suggests the need for more aggressive early interventions.Greater benefits of aggressive treatments were observed in patients with higher serum fibrinogen levels.