Study On The Change Of Concentration Of Plasma C4d During The Treatment Of Idiopathic Membranous Nephropathy

Objective: Complement activation involved in podocyte injury and proteinuria,both CP and LP activation process can produce C4 d.Renal C4 d staining can be used to differentially diagnose immune mediated glomerular diseases from non-immune mediated glomerular diseases.Almost all membranous nephropathy(MN)shows C4 d positive Immunofluorescence.Positive staining of renal M-type phospholipase A2receptor(PLA2R)is a specific biomarker for the diagnosis of idiopathic membranous nephropathy(IMN).The specific antibody to PLA2 R in serum is useful both in diagnosis and monitoring the disease activity.However,the positive rate is only 60%~70%。This study explored the changes of C4 d levels in plasma and urine during treatment of PLA2R-positive IMN.Methods: Plasma C4 d concentration were measured by enzyme linked immunosorbent assay(ELISA)among 187 patients treated with cyclophosphamide(CTX)for 3g~9g and confirmed IMN by renal biopsy.Among them,plasma from 13 pairs of the same patients with CTX treatment were selected at 0g,3g,6g and measured the C4 d levels alone.There are 78 untreated cases,3g CTX treatment 25 cases,6g CTX treatment 43 cases,7~ 9g CTX treatment 41 cases.Results:1.During the treatment with PLA2R-positive MN,plasma C4 d levels decreased with the accumulation of CTX 3g(2.31mg/L to 1.57mg/L),6g(2.31mg/L to1.71mg/L),and 7-9 g(2.31mg/L to 1.65mg/L).2.Initial plasma C4 d levels can predict the remission of PLA2R-positive MN with CTX accumulation at 3g(AUC=0.74,P<0.05,N=25),6g(AUC=0.74,P<0.05,N=43),7-9g(AUC=0.72,P<0.05,N=41).3.Among the13 PLA2R-positive MN patients with complete follow-up,plasma C4 d level could accurately reflect the disease activity and remission at the time of initial untreated and CTX accumulation of 3g(P<0.05)and 6g(P<0.05).4.The initial untreated and CTX accumulation with 3 g,6 g,7 ~ 9 g PLA2 R positive C4 d MN plasma levels shows positive correlation(P < 0.05)with urinary total proteinuria(URTP)and negative correlation(P < 0.05)with serum albumin(s ALB).Conclusion:During the treatment of IMN,the level of plasma C4 d concentration decreased with the process of disease remission。Plasma C4 d concentration can monitor the effect of IMN treatment with hormone combine with CTX and disease development activity.In addition,the beginning concentration of plasma C4 d can predict the sensitivity of CTX using.It may become a new biomarker for the diagnosis and treatment of IMN besides traditional monitoring indicators and serum anti-PLA2 R antibody(PLA2R-Ab)concentrations.