Anti-PLA2R antibody levels are associated with thromboembolism risk in individuals with membranous nephropathy and hypoalbuminemia.

BACKGROUND: Studies to evaluate markers of thrombotic risk in individuals with high-risk membranous nephropathy (MN) are needed. We hypothesized that high anti-phospholipase A2 receptor (PLA2R) titers at the time of severe hypoalbuminemia, reflecting ongoing immunologic disease activity, may be associated with a higher risk of thrombotic complications. METHODS: We conducted a multicenter retrospective cohort study of individuals with membranous nephropathy and serum albumin <2.5 g/dL and evaluated risk factors for first thrombotic events. RESULTS: Sixty-seven individuals met the inclusion criteria. Median serum creatinine was 1.2 mg/dL (Interquartile range [IQR] 0.9-1.6), median urine protein-to-creatinine ratio (UPCR) was 11.9 g/g (IQR 8.5-16.5), and median nadir serum albumin level was 1.9 g/dL (IQR 1.6-2.2). Twenty-four individuals (36%) received no thromboprophylaxis, 20 (30%) received prophylaxis with only antiplatelets, and 23 (34%) received anticoagulation prophylaxis. Thrombotic events occurred in 11 individuals (16%) with incidence rates of 0.11, 0.10, and 0.02 per person-year in the no prophylaxis, antiplatelet, and anticoagulation groups, respectively. In individuals with anti-PLA2R antibody-positive MN who did not receive anticoagulation thromboprophylaxis, higher anti-PLA2R antibody levels were associated with a higher risk of developing thrombotic complications (adjusted Hazard Ratio [HR] = 1.51 per 10 RU/mL increase in PLA2R, 95% Confidence Interval [CI]: 1.10-2.09, P = .012) after adjusting for serum albumin nadir and age. CONCLUSIONS: Higher anti-PLA2R antibody levels at the time of hypoalbuminemia are associated with a higher risk of thrombotic complications in individuals with anti-PLA2R-positive MN.