Value Of Urinary C5a In Monitoring Disease Activity And Prognosis In IgA Nephropathy

BackgroundIgA nephropathy(IgAN) is the most common form of primary glomerulonephritis in the world, is characterized by a predominant deposition of IgA-containing immune complexes in the glomerular mesangium, accompanied by C3 and(or) other immunoglobulins such as IgM,IgG deposition.IgA nephropathy is a relatively benign process,but a major reason of end-stage renal disease(ESRD),over the next 10-20 years,respectively up to10%-15% and 30-40% of affected patients will develop irreversible end-stage renal disease.At present,renal biopsy is a vital means for IgA nephroathy diagnosis,which is invasive and cannot be frequently repeated. Therefore, the development of non-invasive biomarkers would be of great signicance for clinical assessment of IgA nephropathy, which are in urgent need. Previous studies have found that alternative complement pathway actibation plays an important role in IgA nephropathy.Products of complement activation are the cleaved products C3 a and C5a, also terned anaphylatoxins.And C5a is the most important pro-inflammatory cytokines. The aim of this research is to evaluate the predictive value of urinary C5a in IgA nephropathy severity and progression. ObjectiveThe aim of this research is to explore correlations between the levels of urinary C5a with clinical features, renal histopathology and prognosis in patients with IgA nephropathy, providing the foundation for the use of urinary C5a in assessing disease activity and prognosis in IgA nephropathy. MethodsPatients who received renal biopsy for the first time from July 2012 to January 2013 at the Nephrology Department of First Affiliated Hospital of ZhengZhou University were consecutively recruited for the present study.According to Lee's grading system, IgA nephropathy patients are divided into five subgroups: Lee-I(27 cases),Lee-II(31 cases),Lee-III(53 cases),Lee-IV(32 cases),Lee-V(11 cases).Age-and gender-matched controls which included 38 patients with lupus nephritis as the positive controls,28 healthy volunteers were selected in the screening cohort.A whole-stream early moring urine specimen was collected at the of renal biopsy.The urine sample was centrifuged at 3000 R for 5 min at 4?;supernatant was discarded.and stored at-80°C until the time of assays. Then the urinary C5a was detected by enzyme linked immunosorbent assay-sandwich technique(ELISA).To evaluate correlations between the levels of urinary C5a with clinical features, renal histopathology and prognosis in patients with IgA nephropathy. ResultsA total of 153 IgAN patients were admitted in this study,including 82 males and 71 females.1. The levels of urinary C5a in IgAN patients were significantly higher than that of controls respectively(P<0.001). With increasing grades of renal pathology, the levels of urinary C5a were increased(P < 0.001).2. The levels of Urinary C5a positively correlated with serum creatinine(r = 0.515,P < 0.001), urinary protein excretion(r = 0.299, P = 0.001). negatively correlated with eGFR(r =?0.295,P = 0.005).3. Kaplan Meier-analysis showed that patients with high urianary C5a(?1.47 ug/L) had a significantly worse renal outcome during follow-up(Log- rank,P= 0.001). COX regression analysis further confirmed that urinary C5a levels were risk factor of renal prognosis [HR(95%CI)=13.02(3.517-48.204)]. ConclusionsUrinary C5a is closely related with disease severity of injury in IgA nephropathy, high levels of urinary C5a prompted poor prognosis.