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

Barbara Gillespie, MD

Rapid developments in glomerular disease in the past 5 years have warranted evolving approaches to clinical trial design, identifying new biomarkers, and redefining kidney care.

This research is reshaping the understanding and treatment of APOL1-mediated kidney disease, membranous nephropathy, and IgA nephropathy, along with adding to global efforts to refine clinical trial endpoints and accelerate therapeutic development, underscoring key challenges and breakthroughs in the field.

In this Q&A, Barbara Gillespie, MD, and Tobias Huber, MD, discuss advances in glomerular disease research and care at the International Society of Glomerular Disease (ISGD), including biomarker discovery, molecular technologies, and emerging targeted therapies

Both Huber and Gillespie emphasized the importance of collaboration across institutions, societies, and stakeholders, highlighting initiatives such as ISGD and PARASOL as examples of how shared frameworks are accelerating progress in glomerular disease research and care.

: What have been the most significant inflection points in glomerular disease research over the past five years?

Huber: The last five years have been the most dynamic period in glomerular disease research to date. Advances in single-cell and spatial technologies have significantly deepened understanding of disease biology, enabling higher-resolution stratification and identification of new biomarkers. This has improved diagnostic precision, including the emergence of autoantibodies such as anti-nephrin antibodies, which are increasingly linked to specific glomerular diseases.

Therapeutically, the field has also seen multiple successful Phase 3 trials across complement-mediated diseases, B-cell–mediated diseases, IgA nephropathy, and emerging modalities such as CAR T-cell–based approaches in lupus nephritis. In parallel, the creation of the International Society of Glomerular Disease has helped align academia, industry, and regulators, facilitating initiatives such as PARASOL to identify surrogate endpoints like proteinuria in FSGS.

: How has APOL1-mediated kidney disease influenced both research and clinical trial design?

Gillespie: APOL1 has been a major example of how genetic discoveries translate into clinical development. Early work through the Kidney Health Initiative helped establish a roadmap for APOL1 therapeutic programs. However, conducting trials in this space requires meaningful engagement with patients and communities that have historically been underrepresented and, in many cases, have appropriate levels of distrust toward the medical system.

One key lesson has been the importance of meeting patients where they are. In some communities, that has meant engaging faith leaders and churches as trusted sources of education around kidney disease and clinical trials. In one example, outreach through a church-based initiative resulted in nearly all congregants agreeing to be screened for a clinical trial, highlighting the importance of trust and community engagement.

The broader goals have included raising awareness of kidney disease in Black Americans, increasing screening, and improving clinical trial participation. With APOL1 variants identified in 2011, the field has progressed rapidly into Phase 2 and Phase 3 development, demonstrating how quickly precision nephrology can advance when biological targets are well defined.

: How are emerging biomarkers such as anti-nephrin antibodies changing disease classification and management?

Huber: Anti-nephrin antibodies represent a shift toward a more precise understanding of diseases such as minimal change disease, which historically lacked a clear mechanistic basis. Evidence now suggests that a large proportion of adult minimal change disease and even pediatric idiopathic nephrotic syndrome may be driven by autoantibodies.

This has implications for diagnosis, prognosis, and therapeutic decision-making. It also supports a shift away from prolonged steroid exposure toward more targeted B-cell–modulating or depleting therapies. However, a major limitation is that testing remains largely confined to academic centers, and broader clinical adoption will require standardized, commercially available assays.

Clinically, these antibodies may also help guide treatment monitoring and, in some cases, pre-transplant management in patients at high risk of recurrence.

: How is membranous nephropathy informing the development of surrogate endpoints in glomerular disease?

Gillespie: Membranous nephropathy has become a model for precision nephrology, particularly with PLA2R-positive disease, which accounts for approximately 75% to 80% of cases. The availability of measurable antibodies has allowed clinicians to directly link diagnosis, treatment response, and disease activity.

Through PARASOL initiatives, the field is now working to refine surrogate endpoints beyond proteinuria alone by integrating antibody dynamics. This approach may improve trial design and better reflect disease biology. However, a major challenge remains ensuring that antibody measurements are consistently incorporated into clinical trials and registries.

Without that data, opportunities to improve endpoint validation and regulatory pathways are missed.

: How are clinical trial design and execution evolving in glomerular disease?

Gillespie: Clinical trial design has improved significantly, particularly in defining disease-specific endpoints rather than applying a one-size-fits-all approach across glomerular diseases. However, execution remains a challenge, especially in patient recruitment.

Community nephrologists are increasingly central to trial enrollment, and efforts such as clinical trial boot camps aim to expand participation beyond academic centers. This is critical as the number of trials grows and earlier diagnosis increases the pool of potential participants.

Looking ahead, successful trial programs will require not only strong design but also broad engagement across academic and community practice settings.

: What are the key priorities for glomerular disease research heading into 2026?

Huber: Future priorities include continued implementation of surrogate endpoints, refinement of disease-specific trial designs, and improved molecular stratification of glomerular diseases. Advances in molecular imaging and biopsy analysis are expected to shift classification toward true disease endotypes.

Gillespie: There is also growing interest in hierarchical composite endpoints that integrate both clinical and patient-reported outcomes. In addition, the field is moving toward more collaborative models of drug development, including shared data initiatives and cross-industry cooperation.

Other emerging areas include cell and gene therapy, as well as expanded collaboration with specialties such as hematology and oncology, particularly as these modalities enter nephrology.

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

Hopper T, Olabisi OA. APOL1-Mediated Kidney Disease. JAMA. 2024;331(19):1668–1669. doi:10.1001/jama.2024.2667.

Vasquez-Rios G, et al. Novel Therapies in APOL1-Mediated Kidney Disease. Kidney Int Rep. 2023. doi:10.1016/j.ekir.2023.08.028.

Articles

Experts discuss major advances in glomerular disease research and care, including molecular technologies, biomarker discovery, APOL1-mediated kidney disease, and evolving clinical trial design and endpoints.

From APOL1 to Biomarkers, Glomerular Disease Research Is Redefining Kidney Care, With Tobias Huber, MD, Barbara Gillespie, MD

Clinical Trial Summit 2026: Advanced Therapies, Equity, and a Global Outlook for Glomerular Disease

The final episode looks ahead, weaving together summit planning, 2026 goals, cutting-edge therapies, and global equity.

Gillespie previews the International Society of Glomerular Disease (ISGD)’s inaugural Clinical Trial Summit in Galveston, Texas. Designed as a multi-stakeholder meeting, it will bring together basic scientists, trialists, venture capital, regulators, healthcare leaders, patients, study coordinators, and fellows. The format is intentionally interactive, aiming to break silos and “break barriers” in clinical trials.

Huber then proposes a “game” where each shares what they most look forward to by 2026. Their rapid-fire wishes include:

Implementing FSGS surrogate endpoints and widely sharing the work already completed.

Making substantial progress in membranous nephropathy endpoints, including integrating PLA2R titers into qualified surrogate measures.

Defining IgAN 2.0 trial designs as new drugs become standard of care, and learning how to combine multiple approved therapies targeting different points in the disease cascade.

Adapting hierarchical composite endpoints (HCEs) from cardiology, blending clinical outcomes, symptoms, and biomarkers to better reflect patient experience.

Advancing molecular stratification and endotyping of diseases via high-resolution tissue technologies, to eventually replace coarse histologic classifications.

The conversation then turns to cell and gene therapies, referencing an earlier KHI meeting with the 

 Center for Biologics Evaluation and Research (CBER) leaders and the approval of gene therapy for 

They anticipate cell therapies for diabetic kidney disease and membranous nephropathy, as well as gene therapy approaches for IgA nephropathy (IgAN) and Alport syndrome. They determine that success will require close collaboration with hematology and oncology teams already experienced with these modalities.

Huber closes with a reminder that all this high-end innovation must be matched by basic improvements in awareness and early detection, such as routine proteinuria screening, and by solutions for low- and middle-income countries. 

Gillespie adds a vision of glomerular disease centers of excellence, an idea long championed by her mentor Ron Falk, MD, and celebrates the growing cross-society collaboration that will be needed to turn glomerular disease into glomerular health worldwide.

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

, 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

Gale D. RaDaR Validation Confirms PARASOL Findings on FSGS Surrogate Endpoint, with Daniel Gale, PhD, MB BChir. HCPLive. Published June 7, 2025. Accessed March 6, 2026. https://www.hcplive.com/view/radar-validation-confirms-parasol-findings-on-fsgs-surrogate-endpoint

Radhakrishnan J. New Guidelines and Novel Therapies in IgA Nephropathy, With Jai Radhakrishnan, MD. HCPLive. Published 2025. Accessed March 6, 2026. 

https://www.hcplive.com/view/new-guidelines-and-novel-therapies-in-iga-nephropathy-with-jai-radhakrishnan-md

Videos

Experts outline a 2026 vision for glomerular disease care, including new endpoints, combination therapies, and gene therapy advances.

Clinical Trial Summit 2026: Advanced Therapies, Equity, Global Outlook For Glomerular Diseases

Parasol, Endpoints, and Rethinking Clinical Trials in Glomerular Disease

In this episode, the conversation broadens to the PARASOL framework and the evolving science of endpoints and trial design across glomerular diseases.

Gillespie briefly defines PARSOL, which is French for umbrella, as a unifying initiative conceived with leaders like Laurel Damashek to protect and guide the community toward better trial designs and therapeutic options across multiple diseases. PARASOL 1.0 focused on focal segmental glomerulosclerosis (FSGS), and newer extensions now target membranous nephropathy and APOL1-mediated kidney disease, with ambitions to cover many glomerular diseases over the coming decade.

The core philosophy of PARASOL is collaborative data sharing. For example, rather than each company independently shouldering the burden of building evidence for regulatory endpoints, sponsors with competing drugs work together, pooling clinical trial and registry data to evaluate potential surrogate endpoints. Gillespie underscores the importance of this shift, echoing other leading voices in the field who advocate for collaboration as essential to progress in rare and complex diseases.

Gillespie then gives a concise tutorial on endpoints:

In regulatory terms, endpoints must reflect how a patient feels, functions, or survives.

Validated surrogate endpoints (e.g., LDL cholesterol in atherosclerotic disease) have strong, long-term data linking biomarker changes to clinical outcomes.

Reasonably likely surrogate endpoints support accelerated approval, such as proteinuria reductions in IgA nephropathy.

Candidate surrogate endpoints, the focus of Parasol, are being evaluated for their potential to move up the hierarchy.

She notes that while some sponsors try to copy-paste the IgA nephropathy (IgAN) “recipe” to other diseases, this is inappropriate because each glomerular disease has unique pathobiology and mechanisms of action. Hence, disease-specific PARASOL projects for FSGS, membranous, APOL1, and beyond.

The episode also touches on Alport syndrome, where the ASSENT initiative is playing a similar endpoint-defining role, with roughly 45 companies interested.

Finally, Gillespie discusses practical trial challenges, including limited numbers of glomerular specialists, recruitment bottlenecks, and the need to mobilize community nephrologists. She highlights clinical trial boot camps that train new investigators and shows how collaborations with patient organizations are critical for dissemination, pricing, and implementation once drugs are approved.

Neuen B, Wadhwani, S. Kidney Compass: The PARASOL Initiative, with Laura Mariani, MD, MS, and Daniel Gale, PhD, MB BChir. Hcplive.com. Published December 11, 2024. Accessed March 6, 2026. https://www.hcplive.com/view/kidney-compass-the-parasol-initiative-with-laura-mariani-md-ms-and-daniel-gale-phd-mb-bchir

Neuen B. Kidney Compass: PARASOL Findings and Implications for FSGS. HCPLive. Published 2024. Accessed March 6, 2026. https://www.hcplive.com/view/kidney-compass-parasol-findings-and-implications-for-fsgs

The PARASOL initiative is reshaping glomerular disease trials through shared data and improved surrogate endpoints.

PARASOL, Endpoints, and Rethinking Clinical Trials in Glomerular Disease

PLA2R, Membranous Nephropathy, and the PARASOL Membranous Project”

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:

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.

Neuen B, Wadhwani, S. Kidney Compass: The PARASOL Initiative, with Laura Mariani, MD, MS, and Daniel Gale, PhD, MB BChir. Hcplive.com. Published December 11, 2024. Accessed March 6, 2026. 

https://www.hcplive.com/view/kidney-compass-the-parasol-initiative-with-laura-mariani-md-ms-and-daniel-gale-phd-mb-bchir

Neuen B. Kidney Compass: PARASOL Findings and Implications for FSGS. HCPLive. Published 2024. Accessed March 6, 2026. 

https://www.hcplive.com/view/kidney-compass-parasol-findings-and-implications-for-fsgs

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