MO245: Risk Factors for Venous Thrombosis in ANTI-PLA2R + VE AND−VE Primary Membranous Nephropathy: A 6-YEAR Retrospective Analysis
Authors: Lin Henry Wu Hon , Alozai Abdur , Wing Ching LI Jennifer , Elmowafy Ahmed , Ponnusamy Arvind , Jeyalan Vishnu 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Venous thrombosis (VT) is an established cause of increased morbidity and mortality amongst patients with nephrotic syndrome. Previous studies suggest primary membranous nephropathy (PMN) to be associated with the highest risk of developing VT amongst all nephrotic diseases. Antibodies to the phospholipase A2 receptor (anti-PLA2R) is identified as a pathogenic marker to the disease activity of PMN, and considered a strong prognostic marker toward disease progression and treatment response. Recent evidence cites the potential of anti-PLA2R as an independent risk factor of VT in PMN. Nevertheless, the pathophysiology of VT for anti-PLA2R + ve and –ve PMN is not fully known. Whether the common risk factors of VT remain as significant within the anti-PLA2R + ve and –ve PMN context is also not convincingly elucidated of yet. Our study aimed to evaluate and compare risk factors for VT in patients with anti-PLA2R + ve and –ve PMN.

METHOD
This is a retrospective analysis of patients diagnosed with PMN between October 2015 and September 2021. Patients included are age ≥18 years, have biopsy-diagnosed PMN and anti-PLA2R direct immunofluorescence assay testing following PMN diagnosis. Patients excluded were those with secondary causes of membranous nephropathy, history of previous immunosuppression, kidney transplantation before or following PMN diagnosis, or where iatrogenic causes such as major surgery or prolonged immobilization led to VT. Study patients were screened until 28 November 2021 for any VT event and were grouped between those with anti-PLA2R + ve and −ve test results. Demographic and clinical parameters from age, gender, presence of co-morbidities and common risk factors associated with increased risk of VT (hypertension, diabetes mellitus, atrial fibrillation, CHA2DS2-VASC ≥ 3, BMI &gt;30, malignant disease, hormonal treatment and contraceptive pill use), serum and urine biochemical test results at PMN diagnosis (albumin, 24-h proteinuria, proteinuria/albumin ratio, creatinine, eGFR, cholesterol, triglycerides and IgG) were collected. The comparison of demographic and clinical parameters for patients with and without VT in each of the anti-PLA2R + ve and –ve groups was conducted through chi-squared, t and Mann–Whitney U tests. Multivariate regression analysis determined the significance of association between each parameter and VT event occurrence.

RESULTS
Seventy patients with PMN were included in this study, of which 39 patients are anti-PLA2R + ve and 31 patients are anti-PLA2R−ve. Eight patients (20.5%) had VT in the anti-PLA2R + ve group during follow-up whilst this was the case for four patients (12.9%) in the anti-PLA2R−ve group. In both groups, patients with VT were found to have higher serum cholesterol levels (P &lt; 0.05). Lower serum albumin levels, and greater 24-h proteinuria and proteinuria/albumin ratio was observed in patients with VT within the anti-PLA2R−ve group (P &lt; .05). Full results from the multivariate regression analysis are presented in Tables 1 and 2. Serum cholesterol is demonstrated to be significantly associated with VT in the anti-PLA2R + ve (OR 1.42, 95% confidence interval (CI) 1.12–1.72) and anti-PLA2R−ve groups (OR 1.45, 95% CI 1.15–1.76), respectively. Serum albumin (OR 0.72, 95% CI 0.49–0.96), 24-h proteinuria (OR 1.33, 95% CI 1.03–1.63) and proteinuria/albumin ratio (OR 1.32, 95% CI 1.04–1.59) are shown to be significantly associated with VT within the anti-PLA2R−ve group.

CONCLUSION
There is supporting evidence that serum cholesterol, albumin and proteinuria may all present as important markers of risk prediction for VT in patients with PMN, though this will require further validation in prospective multi-center studies with larger patient samples. Close monitoring of these markers, and early intervention in response to hypercholesterolemia, hypoalbuminemia and proteinuria with consideration of anti-PLA2R status should ensue as part of primary prevention strategies to reduce VT incidence in the PMN population.