Abstract: PUB170
Treatment of High-Titer Phospholipase A2 Receptor Autoantibody Membranous Nephropathy with Rituximab
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Haas, William Michael, University of Pittsburgh Division of Renal-Electrolyte, Pittsburgh, Pennsylvania, United States
- Tan, Roderick J., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
- Ramkumar, Mohan, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
Introduction
Membranous nephropathy (MN) accounts for ~20% of nephrotic syndrome cases. The vast majority are idiopathic and caused by circulating autoantibodies targeting the M-type phospholipase A2 receptor (PLA2R) on podocytes. Subepithelial immune deposits and complement activation cause podocyte injury and proteinuria. Diagnosis can be established with serological testing for anti-PLA2R antibodies, but the optimal treatment of high-titer antibodies is not well described.
Case Description
A 49-year-old male with a history of type-1 diabetes mellitus, hypertension, alcohol-use disorder and tobacco use presented with a sudden onset of bilateral lower extremity edema in July of 2025. Serum creatinine was 0.9-1.1 mg/dL and serum albumin was 1.7 g/dL with a spot urine protein-to-creatinine ratio (PCR) of 9.2 g/g. MN was diagnosed with a PLA2R titer of 1341 RU/mL (negative < 14). Although Obinutuzumab was considered due to the high titer, the patient was ultimately treated with Rituximab (1 g x 2 doses, 14 days apart) along with losartan, spironolactone, cyclosporine, and apixaban. Three months after rituximab, the PLA2R decreased to 123.9 RU/mL and B cell levels were 1 cell/uL (reference range: 79-574 cells/uL). PCR remained elevated at 8.9 g/g. The treatment plan is to evaluate the PLA2R antibody levels at the 6 month timepoint and re-dose with Rituximab if not fully suppressed, or switch to Obinutuzumab.
Discussion
This case highlights three important points regarding treatment of MN with high titer PLA2R. First, a significant reduction in antibody level, even with high starting titers, can be achieved through Rituximab induction as primary immunosuppressive modality. Second, B-cell depletion is correlated with a reduction in PLA2R burden, highlighting its effectiveness as a viable option to monitor therapeutic efficacy. Third, the reduction in PLA2R antibody precedes clinical improvement.