Abstract
KEY POINTS: Higher serum phospholipase A2 receptor antibody is an independent risk factor of arterial and venous thromboembolic events in patients with primary membranous nephropathy. The inflammatory system may play a role in this relationship. BACKGROUND: This study investigated risk factors and possible mechanisms of arterial and venous thromboembolic events in patients with primary membranous nephropathy (pMN). METHODS: Patients with pMN confirmed by renal biopsy from June 1, 2010, to March 3, 2023, were included, and the study outcome was set as a composite end point of acute coronary syndrome, heart failure, cerebral infarction, arrhythmia, pulmonary embolism, deep venous thrombosis, and all-cause mortality. RESULTS: A total of 433 pMN patients with complete data were included, with a median follow-up time of 73 (45.5–101.6) months and a composite end point rate of 10.2%. We divided all patients with events into an early event group (events occurring in the first 2 years after renal biopsy) and a late event group (events occurring after 2 years after renal biopsy) according to the time of event. It showed a lower serum albumin and higher baseline value of serum phospholipase A2 receptor (PLA2R) antibody titer and mean value of each follow-up in the early event group compared with the late event group. Cox proportional hazards model showed that after adjusting for confounding factors, in addition to older age, history of deep vein thrombosis and higher urinary protein, higher baseline serum PLA2R antibody titers (odds ratio [OR], 1.034; 95% confidence interval [CI], 1.006 to 1.063; P = 0.015), and high high-sensitivity C-reactive protein level (OR, 1.049; 95% CI, 1.002 to 1.098; P = 0.041), renal pathology with segmental sclerotic lesions (OR, 3.480; 95% CI, 1.338 to 9.050; P = 0.011) were also independent risk factors for the occurrence of end point events. The results also showed that baseline serum IL-6 levels were significantly higher in the event group compared with the nonevent group (4.25 versus 3.21 pg/ml), and the difference was statistically significant (P = 0.009). CONCLUSIONS: In the early event group, higher serum PLA2R antibody and renal pathology with segmental sclerosis lesions may affect the occurrence of cardiovascular, cerebrovascular, and venous thrombotic events. The inflammatory system may play a role in this relationship.