The Role Of C3a,C5a In Focal Segmental Glomerulosclerosis

BackgroundFocal segmental glomerulosclerosis(FSGS)usually manifests as proteinuria in the range of nephrotic syndrome,with pathological manifestations of focal and segmental glomerular sclerosis.The incidence of FSGS is increasing recently and FSGS is becoming more common in adult glomerular diseases.Nearly 50% of patients who fail to achieve proteinuria relief will progress to end stage renal disease within 5-10 years.In addition,20-25% of patients will have recurrent diseases after kidney transplantation and a higher risk of recurrence in the transplanted kidney.I t is also difficult for the treatment of FSGS.FSGS is not sensitive to glucocorticoids,and it has high resistance rate,long treatment duration,and poor therapeutic effect.The exact pathogenesis of FSGS is still unclear.Previously,studies focused on non-immune factors such as mechanical stress,genetic mutation and cyclic permeability factor,which lead to podocyte injury.In recent years,it is demonstrated that C3 deposites in the glomerular segmental sclerosis region in immunofluorescence,and 85% of C1 q nephropathy has a light pathological manifestation of FSGS.Thus,we hypothesize that complement activation may be involved in the pathogenesis of FSGS.C3 a and C5 a are small cleavage fragments produced by complement activation and they are the major pro-inflammatory effector molecules that exert a broad pro-inflammatory effect by binding to specific receptors.Our study aimed to investigate the role of C3 a and C5 a in FSGS and hope to provide new directions and ideas for the treatment of FSGS.ObjectiveTo study the role of C3 a and C5 a in focal segmental glomerulosclerosis(FSGS).Methods(1)A tocal of 66 patients with FSGS confirmed by renal biopsy were selected,including 18 cases of tip lesion,11 cases of perihilar,22 cases of not otherwise specified(NOS),10 cases of cellular,and 5 cases of collapsing FSGS.The normal renal tissues resected from patients with kidney tumor were taken as negative controls.The expressions of C3 a and C5 a in renal tissues were detected by immunohistochemistry.(2)Sixty-six patients with FSGS were selected,and 10 healthy adult controls were selected from the same physical examination center as normal in the same term.The levels of C3 a and C5 a in serum and urine were detected by ELISA.Results(1)Immunohistochemical results showed that C3 a and C5 a were deposited in glomerulus of FSGS patients,and no deposition in normal renal tissues.Kidney C3 a score was significantly associated with serum creatinine(r=0.547,P<0.001)and proteinuria(g/24h)(r=0.329,P=0.007)in FSGS patients.Kidney C5 a score was significantly associated with serum creatinine(r=0.415,P<0.001)and proteinuria(g/24h)(r=0.414,P<0.001)in FSGS patients.(2)The levels of serum C3 a and C5 a in FSGS patients were higher than those in healthy adults(P<0.05),but there was no significant difference among the different pathological types(P>0.05).Urinary C3a/urinary creatinine,urinary C5a/urinary creatinine levels were higher in FSGS patients than in healthy adults(P<0.05).The urine C3a/urinary creatinine and urinary C5a/urinary creatinine levels were higher in collapsing FSGS than other FSGS types(P<0.001),but there was no significant difference among the tip lesion,the perihilar,the not otherwise specified and the cellular(P>0.05).(3)The urinary C3a/urinary creatinine levels were significantly associated with serum creatinine(r=0.774,P<0.001)and proteinuria(g/24h)(r=0.430,P<0.001)in FSGS patients.The urinary C5a/urinary creatinine levels were significantly associated with serum creatinine(r=0.677,P<0.001)and proteinuria(g/24h)(r=0.333,P=0.007)in FSGS patients.Conclusions(1)Complement C3 a and C5 a participate in the occurrence of FSGS and could play an important role in the development of FSGS.(2)The degree of the activation of complement C3 a,C5a may relate to the severity of FSGS.