Analysis Of Risk Factors Of Vein Thrombosis And Hypercoagulability In Patients With Primary Membranous Nephropathy

BackgroundVenous thromboembolism(VTE)is a common complication in patients with nephrotic syndrome(NS).Primary membranous nephropathy(PMN)is associated with the highest risk for developing venous thrombosis compared with other nephrotic diseases.Whether the pathognomonic anti-phospholipase A2 receptor(PLA2R)antibody as risk factors for VTE in PMN was reported by a few studies.The effect of plasma proprotein convertase subtilisin/kexin type 9(PCSK9)on hemostasis and thrombosis has been studied in other diseases such as coronary heart disease and type II diabetes.To date,there have been no studies on the association between elevated circulating PCSK9 concentrations and hypercoagulable states in patients with nephropathy.Aims1.Assess the predictive value of anti-PLA2R antibody with regard to incidence of venous thrombosis in PMN.2.Explore the potential associations between PCSK9 and coagulation indexes in patients with PMN.Methods1.A retrospective analysis was performed on 365 in-hospital patients diagnosed with PMN at Shandong Provincial Hospital from January 2018 to August 2021.Anti-PLA2R antibody was detected by commercial enzyme-linked immunosorbent assay(ELISA).Multivariate logistic regression was used to detect the independent risk factors for venous thrombosis.2.A total of 87 patients diagnosed with PMN at Shandong Provincial Hospital from March 2021 to September 2022 were enrolled in this study.30 healthy participants were recruited to match PMN participants according to age and sex.Plasma PCSK9 and tissue factor(TF)concentrations were tested by ELISA.Correlations between PCSK9 and coagulation abnormalities in patients with PMN was analyzed using univariate and multiple linear regression analysis.Results1.37 patients(10.14%)had venous thrombosis.Patients with venous thrombosis had higher levels of cholesterol(CHOL),low density lipoprotein(LDL),and D-dimer than those without venous thrombosis(P<0.05).Patients with venous thrombosis had significantly lower levels of albumin(P=0.049).No significant differences were found in proteinuria,serum creatinine(SCR),estimated glomerular filtration rate(eGFR),platelets(PLT)and fibrinogen between patients with and without thrombosis.Anti-PLA2R antibody levels in patients with venous thrombosis were significantly higher than in patients without it(P=0.004).In the univariate logistic regression,anti-PLA2R antibody(OR:1.340;P=0.004),albumin(OR:0.945;P=0.050),cholesterol(OR:1.191,P=0.006),and low density lipoprotein(LDL)(OR:1.271,P=0.006)were associated with venous thrombosis.Ln anti-PLA2R antibody(OR=1.269;95%CI:1.032～1.561),and LDL(OR=1.213;95%CI:1.017～1.448)were the independent risk factors for venous thrombosis(P<0.05)in multivariate analysis.2.Plasma PCSK9 levels in patients with PMN were significantly higher than that in healthy controls(P=0.001).Plasma levels of PCSK9 were positively correlated with factorⅧ,factor Ⅸ,factor Ⅺ,TF,protein C and protein S(r=0.267,P=0.013;r=0.496,P<0.001;r=0.217,P=0.045;r=0.584,P<0.001;r=0.372,P=0.001;r=0.282,P=0.011).In multiple linear regression analysis,PCSK9 concentration was independently and positively correlated with factor Ⅷ,factor Ⅸ,and TF(β=0.186,P=0.047;β=0.325,P=0.001;β=0.531,P<0.001;respectively).PCSK9 concentration was independently and negatively correlated with PT(P=-0.343,P=0.011).Conclusions1.Anti-PLA2R antibody was the independent risk factor for venous thrombosis in PMN.Larger prospective studies were warranted to verify the results in future.2.Plasma PCSK9 levels had good positive correlations with procoagulant clotting factors and negative correlations with PT in PMN,which might provide novel information with regard to PCSK9 and hypercoagulability in PMN.