Effect of Phospholipase A2 Receptor (PLA2R) Antibody and Inflammatory Factors on Cardiovascular and Thromboembolic Events in Patients with Primary Membranous Nephropathy

Background: Primary membranous nephropathy (pMN) is the most likely cause of venous thromboembolic complications in all pathological types of NS, as well as arterial thrombotic events, especially cardiovascular events. What are the high-risk groups for arterial and venous thromboembolic events in patients with pMN? Why are arterial and venous thromboembolic events likely to occur in this population? Methods: Patients with pMN diagnosed by renal biopsy in our hospital from June 1, 2010 to March 3, 2023 were included. The study outcome was set as a composite of ACS, HF, stroke, arrhythmia, VTE, pulmonary embolism and all-cause mortality. Results: A total of 433 patients were included, with a median follow-up of 75 months. The proportion of composite endpoint was 8.1%. Univariate analysis showed that the event group had a higher proportion of males, smokers, with hypertension, a previous history of venous thromboembolism, a higher amount of urinary protein, a higher blood PLA2R antibody titer, a higher hsCRP level, and a higher D-dimer and FDP level than the non-event group. Cox proportional hazards model results showed that both high blood PLA2R antibody titer (OR 1.045, 95%CI 1.013-1.078, P=0.006) and high hsCRP levels were independent risk factors for the occurrence of endpoint events (OR 1.057, 95%CI 1.002-1.115, P=0.041).The results of correlation analysis showed that there was a correlation between blood PLA2R antibody titer and hsCRP level (r=0.185, P<0.001), so we inferred that blood PLA2R antibody may lead to endothelial cell injury through an inflammatory mechanism, causing cardiovascular events or thromboembolic events. We initially detected IL-6 levels in the enrolled patients, and the results showed that IL-6 levels were 5.58±4.44pg/ml in the cardiovascular and thromboembolic event groups and 2.95±1.22pg/ml in the non-event group, and the difference between the two groups was statistically significant (p=0.015). Conclusion: Both high serum PLA2R antibody titer and high hsCRP level are independent risk factors for cardiovascular events or thromboembolic events in patients with pMN, and IL-6 level is significantly increased in the event group, which may suggest that serum PLA2R antibody and inflammation play a role in the mechanism of pMN and provide a basis for our subsequent basic experiments.