From APOL1 to Biomarkers, Glomerular Disease Research Is Redefining Kidney Care, With Tobias Huber, MD, 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.1

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 therapies2

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.

HCPLive: 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.

HCPLive: 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.

HCPLive: 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.

HCPLive: 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.

HCPLive: 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.

HCPLive: 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.

References

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

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