Welcome to Travere Therapeutics’ Rare Kidney Disease Show podcast, where rare kidney disease gets a spotlight. Host Dr. Chris Gisler, Senior Medical Director at Travere Therapeutics, is joined by Dr. Daniel Gale and Dr. Gaia Coppock for a practical and evidence-driven conversation on FSGS, proteinuria, and what registry and clinical data mean for clinical decision-making.

In this episode, Dr. Gaia Coppock reflects on how the heterogeneous nature of focal segmental glomerulosclerosis (FSGS) has historically been challenging for clinicians and highlights we are working towards a new era of research, diagnosis, and therapeutics. From there, the discussion focuses on FSGS as a podocytopathy, outlining different triggering events that converge on podocyte injury and shared downstream pathways. Dr. Daniel Gale goes on to discuss how RaDaR, PARASOL, and other real-world datasets have helped clarify the relationship between proteinuria remission and long-term kidney outcomes.

The conversation also explores the Phase 3 DUPLEX study. Dr. Coppock reviews the study design and key findings, including reductions in proteinuria, data on complete remission, safety profiles, and the challenges of interpreting estimated glomerular filtration rate (eGFR) slope in a complex and heterogeneous condition like FSGS.

Together, experts reflect on where FSGS care is heading, underscoring the importance of targeting lower proteinuria thresholds, improving diagnostic precision, and adopting multi-targeted approaches.

Speakers:

• Dr. Chris Gisler is a medical director at Travere Therapeutics and an adult Nephrologist
• Dr. Daniel Gale, MBBS, PhD (Professor of Nephrology, University College London. Director, RaDaR/Rare Renal Registry)
• Dr. Gaia Coppock, MD (Assistant Professor of Clinical Medicine, Renal-Electrolyte and Hypertension. University of Pennsylvania/Penn Medicine)

Key Takeaways:

• FSGS is a heterogeneous pattern of injury, not a single condition. FSGS can arise from multiple causes, which has historically made diagnosis, treatment, and clinical trial design difficult
• Proteinuria is one of the most important clinical signals in FSGS. RaDaR and PARASOL have helped validate what clinicians have long suspected: lower proteinuria targets matter, and proteinuria can serve as a meaningful predictor of disease activity and response
• DUPLEX , especially in a condition where eGFR slope can be difficult to assess because of heterogeneity, hyperfiltration, and variability in kidney function
• The future of FSGS care depends on pushing to achieve the lowest proteinuria targets possible while becoming more precise in diagnosis and treatment

Key Quotes:

• “Proteinuria really represents a very strong biomarker of disease activity, rather than simply a readout of how much damage has occurred in the kidney.” (6:08)
• “I think that clinicians should push harder with FSGS. You know, don't stop until you've exhausted all options and really push to get to the lowest proteinuria target possible.” (25:59)
• "I think the use of FSGS as a disease label is now really established to be doing more harm than good for many patients. It's the start of the diagnostic journey, not the end of it.” (26:27)

Disclaimer:
Guest speakers of the Rare Kidney Disease Show may be paid consultants of Travere Therapeutics. This podcast episode was recorded on June 9, 2026. Please always consult updated sources for the latest information, as information discussed may have changed since the recording date.

Welcome to Travere Therapeutics’ Rare Kidney Disease podcast, where rare kidney disease gets a spotlight. Host Chris Gisler brings together two leading voices in nephrology, Dr. Donald Kohan and Dr. Yelena Drexler, for an energetic conversation about why proteinuria matters so much in FSGS and IgA nephropathy.

What starts as a discussion of proteinuria as a lab value soon deepens: what is it, why does it mean more than just numbers, and how does it actually drive kidney injury?

Dr. Donald Kohan breaks down the biology of endothelin, showing its role at every stage of glomerulonephritis. Then, Dr. Yelena Drexler links research to real patient care and shares the practical impact of proteinuria on outcomes.

Whether you’re a clinician, researcher, or patient advocate, this episode delivers clear takeaways—from the latest studies shaping proteinuria targets to the call for multi-pathway, biology-informed treatment strategies.

Speakers:

• Dr. Chris Gisler is a medical director at Travere Therapeutics and an adult Nephrologist
• Dr. Donald Kohan is a Professor of Medicine, Division of Nephrology & Hypertension at the University of Utah
• Dr. Yelena Drexler is an Associate Professor of Clinical Medicine, Division of Nephrology & Hypertension at the University of Miami

Key Takeaways:

• Proteinuria is both a marker and a driver of FSGS and IgAN, actively fueling inflammation, fibrosis, and a “vicious cycle” of ongoing injury, thereby making early and sustained reduction a critical treatment goal
• Podocyte injury is the central pathway in glomerular diseases like FSGS, with diverse causes converging on podocyte loss, leading to proteinuria and irreversible kidney damage
• Endothelin is a key mechanistic driver across the kidney, directly damaging podocytes and other cell types while working synergistically with the renin-angiotensin system to accelerate disease progression

Key Quotes:

• “Fundamentally, FSGS is a podocytopathy. And proteinuria is so important because it's a signature of podocyte loss, it's a signature of podocyte injury” 07:48
• “Persistent proteinuria to me is really a sign of ongoing podocyte injury and ongoing podocyte loss and the formation of sclerosis, focal and segmental glomerulosclerosis, that ultimately is irreversible. And we want to intervene to prevent that” 10:47
• “We’re not just thinking about proteinuria as a marker of disease. Proteinuria itself can actually worsen kidney injury… And you end up with a vicious cycle - the more injury you get, the more proteinuria you get and then the cycle continues” 11:23
• "As we're thinking about targeting the endothelin system, we have to think this system is activated throughout the entire course of the disease. And if we're going to target it, we've got to target it throughout the entire course of the disease” 17:50

Disclaimer:

Guest speakers of the Rare Kidney Disease Show may be paid consultants of Travere Therapeutics. This podcast episode was recorded on March 6, 2026. Please always consult updated sources for the latest information, as information discussed may have changed since the recording date.

In this episode, Drs. Jonathan Barratt and Shikha Wadhwani discuss findings from the SPARTAN study, a Phase 2 open-label, single-arm trial evaluating sparsentan in 12 treatment-naïve patients with IgA nephropathy. The conversation explores the trial’s design, including assessments of proteinuria reduction and urinary biomarkers to better understand sparsentan’s mechanism of action.

Results from SPARTAN demonstrate a 69% mean reduction in proteinuria at 24 weeks, alongside biomarker trends consistent with decreased glomerular inflammation.

Dr. Barratt notes that no new safety signals emerged, with hypotension observed at a rate consistent with prior studies and no adverse hepatic events reported.

Together, the experts reflect on how these data support the biological plausibility of sparsentan’s anti-inflammatory properties and may inform the development of biomarker-guided strategies in IgA nephropathy, including ongoing evaluation of sparsentan in the PROTECT trial.

Key Takeaways:

• SPARTAN demonstrated a robust mean reduction in proteinuria (~69%) in treatment-naïve patients with IgA nephropathy after 24 weeks of sparsentan therapy.
• Biomarker analysis revealed reductions in markers of macrophage activation, complement activity, and inflammatory cytokines, supporting the hypothesis of a potential anti-inflammatory effect.
• No new safety signals were observed; hypotension rates were consistent with earlier trials, and no clinically significant changes in hepatic function were reported.
• These findings contribute to our mechanistic understanding of sparsentan and provide a framework for future investigation of biomarkers from samples from larger studies such as PROTECT.

Speakers:

• Dr. Jonathan Barratt, PhD, FRCP. Professor of Renal Medicine at the University of Leicester, where he leads the IgA Nephropathy Research Programme. He is internationally recognized for his leadership in translational and clinical research in glomerular diseases, particularly IgA nephropathy. Dr. Barratt directs the UK’s Rare Disease Group for the UK National Registry of Rare Kidney Diseases (RaDaR).
• Dr. Shikha Wadhwani, MD, MS, FASN. Associate Professor of Medicine in the Division of Nephrology and Vice Chair of Clinical Research in the Department of Medicine at University of Texas Medical Branch. She is also the inaugural Associate Research Officer for clinical research, overseeing clinical trials across all 5 schools at UTMB. She is the founding member of the International Society of Glomerular Disease (ISGD) and is steering a global effort aimed at supporting the growth and success of physician-trialists. In her spare time, Dr. Wadhwani co-hosts a podcast called Kidney Compass: Navigating Clinical Trials.

Disclaimer:

Guest speakers of the Rare Kidney Disease Show may be paid consultants of Travere Therapeutics. This podcast episode was recorded on July 25, 2025. Please always consult updated sources for the latest information, as information discussed may have changed since the recording date.