Abstract: FR-PO0810
Is Antibody Clearance Enough? Immunologic Remission Frequently Fails to Translate into Proteinuria Resolution in Phospholipase A2 Receptor (PLA2R)-Associated Membranous Nephropathy
Session Information
- Glomerular Diseases: Practice and New Concepts Shaping Modern Care
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Patel, Nilang G., Richmond VA Medical Center, Richmond, Virginia, United States
- Gupta, Naman, Richmond VA Medical Center, Richmond, Virginia, United States
- Silvey, Scott, Richmond VA Medical Center, Richmond, Virginia, United States
- Kidd, Jason M., Virginia Commonwealth University, Richmond, Virginia, United States
- Athavale, Ambarish, University of California San Diego, La Jolla, California, United States
Background
In PLA2R antibody–associated membranous nephropathy(MN), immunological clearance(IC) is used as a surrogate treatment endpoint. There is uncertainty on whether current ELISA–based thresholds accurately define IC.
Methods
We performed a retrospective analysis of adults with primary MN from the VHA and TriNetX US cohorts (2015–2025). Inclusion criteria were proteinuria ≥1000 mg/g and positive PLA2RAb (≥19 RU/mL). Patients with ESRD, kidney transplant, eGFR ≤15 mL/min/1.73 m2, or secondary causes were excluded. IC was defined as PLA2RAb <14 RU/mL by ELISA or negative immunofluorescence(IF). Proteinuria outcomes were assessed up to 24 months after IC. Complete remission(CR) was defined as proteinuria ≤300 mg/g; partial remission(PR) as ≥50% reduction from baseline with final proteinuria >300–≤3500 mg/g.
Results
In the VHA cohort, 195 patients were included; 112 had follow–up PLA2RAb testing, and 53 (47%) achieved IC. Despite IC, only 49% achieved CR and 38% PR. Rituximab use was significantly higher among immunological responders (60% vs. 34%, p=0.009). Higher baseline proteinuria was associated with failure to achieve CR.
In the TriNetX cohort, 283 of 538 patients had repeat PLA2RAb testing; 140 (50%) achieved IC. Among those with follow–up proteinuria data, 64% reached CR and 22% PR. Importantly, restricting IC definition to ELISA–only testing reduced observed CR rates (56% vs. 64% with ELISA+IF), suggesting systematic underestimation of both immunological and clinical response.(Fig 1)
Conclusion
In large real–world cohorts, immunological clearance occurs in only half of patients with PLA2R–associated MN and fails to reliably predict complete proteinuria remission. Dependence on current ELISA–only thresholds (<14 RU/mL) may overestimate antibody clearance; adding negative immunofluorescence improves complete remission prediction. These findings challenge current surrogate endpoints and underscore the need to recalibrate immunological remission definitions in MN.