Coagulation Disorders And Platelet Hyperactivity In Patients With Idiopathic Membranous Nephropathy

Membranous nephropathy(MN)is a common cause of idiopathic nephrotic syndrome in adults.The formation of subepithelial deposition of immune complex and complement activation result in podocyte injury,causing mass proteinuria.According to the difference in etiology,membranous nephropathy is divided into idiopathic membranous nephropathy(IMN)and secondary membranous nephropathy.Phospholipase A2 receptor located on the podocytes is considered to be the main antigen of idiopathic membranous nephropathy.Thromboembolism is a common complication in idiopathic membranous nephropathy.Coagulation disorders are fundamental to thromboembolism.Regarding to the underlying mechanism of hypercoagulable state in idiopathic membranous nephropathy patients,previous studies mostly focus on the imbalance of pro-and anti-coagulant factors caused by nephrotic syndrome state.But in fact,there are still controversies about the mechanisms of the coagulation disorders of idiopathic membranous nephropathy.Hence,our study aims at evaluating the coagulation function of idiopathic membranous nephropathy patients,and further investigating the specific manifestations and influencing factors of the coagulation disorders in idiopathic membranous nephropathy.Part I The characteristics of the coagulation disorders in patients with idiopathic membranous nephropathyIn this part we retrospectively involved in 242 patients with nephrotic syndrome who had undergone renal biopsy with the diagnosis of idiopathic membranous nephropathy from January 2012 to September 2016 in our clinical research center,and analyzed their thromboelastogram parameters such as R time,K time,a angle,MA value,and CI.Besides,we took 81 idiopathic membranous nephropathy patients with 24h urinary protein?1g as control group.Significant difference was noticed in MA value between idiopathic membranous nephropathy with nephrotic syndrome group and control group(69.6 vs.65.1mm,P<0.01),but not in R time(6.0vs.6.1 min,P=0.72).With regard to idiopathic membranous nephropathy patients with nephrotic syndrome,correlation analysis showed that Alb was negatively related to MA value(r=-0.19,P<0.01),a angle(r=-0.16,P=0.01)and CI(r=-0.13,P=0.05),positively related to K time(r=0.12,P=0.06),but not related to R time(r=0.01,P=0.87).Multiple linear regression analysis indicated that serum albumin was an independent relevant factor of platelet hyperactivity in idiopathic membranous nephropathy.And there were no differences in all the clinical characteristics and TEG parameters between PLA2R antibody(+)and PLA2R antibody(-)idiopathic membranous nephropathy patients with nephrotic syndrome.Besides,we divided 242 idiopathic membranous nephropathy patients with nephrotic syndrome into MA70 group(129 patients)and MA>70 group(113 patients)according to MA value.Compared with MA70 group,MA>70 group showed worsen renal function,lower hemoglobin and hematocrit,higher platelet count and triglyceride.However,there were no significant differences in serum albumin and proteinuria between these two groups.Part ? The characteristics of platelet function in patients with idiopathic membranous nephropathyWe have analyzed the coagulation disorders of idiopathic membranous nephropathy in different disease states by thromboelastogram in Part I,and found out platelet hyperactivity may exist in patients with idiopathic membranous nephropathy.Now we further analyzed the platelet activation biomarkers by flow cytometry to validate the platelet hyperactivity of idiopathic membranous nephropathy patients.In this part we involved in 20 patients with nephrotic syndrome who had undergone renal biopsy with the diagnosis of idiopathic membranous nephropathy in our clinical research center,and analyzed their percentage of CD62P and PAC-1.Besides,we took 21 volunteers as control group.Significant difference was noticed in percentage of CD62P between idiopathic membranous nephropathy with nephrotic syndrome group and control group,but no difference was found in percentage of PAC-1.PAC-1 is the biomarker of early stage platelet activation,while CD62P represents the late stage of platelet activation.These indicate that late stage platelet activation exists in the idiopathic membranous nephropathy patients,which further validate the platelet hyperactivity in patients with idiopathic membranous nephropathy.In conclusion,platelet hyperactivity is correlated closely to the coagulation disorders of idiopathic membranous nephropathy.Platelet hyperactivity is related to nephrotic syndrome state,but not PLA2R antibody.These results imply that combination of anticoagulant and anti-platelet therapy may decrease the incidence of thromboembolic events in idiopathic membranous nephropathy.