The Changing Landscape of Glomerular Disease Research and Treatment - Episode 4

PLA2R, Membranous Nephropathy, and the PARASOL Membranous Project

Published on: March 6, 2026

Strategic Alliance Partnership | <b>International Society of Glomerular Disease (ISGD)</b>

PLA2R antibodies are advancing precision care in membranous nephropathy and informing new surrogate endpoints through PARASOL.

This episode builds a bridge from anti-nephrin autoantibodies to PLA2R-positive membranous nephropathy, positioning the latter as a role model for precision nephrology.

Gillespie recalls work with NEF Cure around the years 2021 to 2023, when they evaluated ongoing membranous nephropathy trials to see how frequently anti-PLA2R antibodies were being measured. To their disappointment, several sponsors were not systematically collecting PLA2R data, a missed opportunity when the goal is to support surrogate endpoints beyond proteinuria.

Gillespie emphasizes how steroids are poorly tolerated, sharing her own short-term experience versus patients who endure months or years of therapy. She highlights that antibody dynamics can precede changes in proteinuria: if PLA2R (or other autoantibody) titers fall before proteinuria improves, this could justify earlier tapering of toxic therapies, rather than waiting 3 to 6 months for proteinuria to decline. This is the clinical promise of antibody-based endpoints.

Huber then situates PLA2R-positive membranous nephropathy in the broader history. It represents a rare full success story where the community:

Identified a causal antigen (PLA2R)
Developed a measurable biomarker
Linked this to B cell–depleting therapies, such as rituximab, establishing precise, mechanism-based treatment.

Since commercial PLA2R assays have been available for over a decade, centers worldwide have accumulated large datasets, creating fertile ground for advanced analyses. This is the foundation for the PARASOL membranous project under the International Society of Glomerular Disease (ISGD). The project’s aim is to refine proteinuria-based surrogate endpoints by integrating PLA2R antibody titers, measuring not only the effect on the symptom, proteinuria, but also on the molecular cause.

Huber describes alignment with regulators and stakeholders to pursue endpoint qualification that includes PLA2R dynamics. The project encompasses building global registries, aggregating and harmonizing existing datasets, and correlating antibody kinetics with outcomes. The ultimate goal is to create stronger, more predictive endpoints that will support better trial design, faster drug development, and improved decision-making in membranous nephropathy.

Featured Experts

Barbara Gillespie, MD, Chief Medical and Strategy Officer of the International Society of Glomerular Disease and Adjunct Professor at the University of North Carolina

Tobias Huber, MD, President of the International Society of Glomerular Disease, Chair of the Center of Internal Medicine; Director of the III. Department of Medicine (Nephrology, Rheumatology, Endocrinology and Transplantation); and Director of the Hamburg Center for Kidney Health at the University Medical Center Hamburg-Eppendorf

Editors’ Note: Gillespie reports no relevant disclosures. Huber reports relevant disclosures with Boehringer Ingelheim, Novartis, Alexion, Pfizer, Retrophin-Travere, and Fresenius Medical Care.