Kidney Compass: Navigating Clinical Trials

Kidney Compass: Navigating Clinical Trials
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Hosted by Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, Kidney Compass: Navigating Clinical Trials is a regular podcast exploring and breaking down the latest updates and nuances of clinical trials in nephrology. By listening to Kidney Compass, you'll get the guidance you need to navigate the changing landscape of clinical trials across the spectrum of kidney disease.

  1. REMODEL Trial Provides Mechanistic Rationale for Semaglutide in CKD

    APR 14

    REMODEL Trial Provides Mechanistic Rationale for Semaglutide in CKD

    At the World Congress of Nephrology 2026 in Yokohama, Japan, growing attention is being paid not just to whether therapies improve outcomes in chronic kidney disease, but how they work at a mechanistic level. In this episode of Kidney Compass, host Brendon Neuen, MBBS, PhD, spoke with David Cherney, MD, PhD, about the REMODEL trial, a mechanistic study designed to better understand the kidney-protective effects of semaglutide in patients with type 2 diabetes and chronic kidney disease. 0:00:00 – Episode intro & guest setup0:00:54 – What is REMODEL & link to FLOW0:01:21 – Design, outcomes & mechanistic readouts of REMODEL0:04:30 – Additive effects with SGLT2 inhibitors0:07:17 – Perirenal fat, venous pressure & “toxic adiposity”0:10:28 – Relevance to non‑diabetic CKD & SMART trial link0:13:20 – Clinical messaging & patient communication https://www.hcplive.com/view/kidney-compass-remodel-trial-provides-mechanistic-rationale-for-semaglutide-in-ckd

    15 min
  2. IV Iron and Functional Outcomes in Kidney Transplant Recipients

    APR 14

    IV Iron and Functional Outcomes in Kidney Transplant Recipients

    Iron deficiency is increasingly recognized as a clinically meaningful yet underexplored contributor to morbidity in kidney disease, extending beyond its traditional association with anemia. In populations such as kidney transplant recipients, where graft function may be stable, many patients continue to experience impaired physical function, reduced quality of life, and lingering fatigue. As evidence from other fields, particularly cardiology, has begun to demonstrate the benefits of intravenous iron on functional outcomes independent of hemoglobin, questions are emerging about whether similar strategies could improve how patients with kidney disease feel and function, not just how they measure on laboratory parameters. In this episode of Kidney Compass recorded on-site at World Congress of Nephrology in Yokohama, Japan, hosts Shikha Wadhwani, MD, MS, and Brendon Neuen, MBBS, PhD, spoke with Martin de Borst, MD, PhD, about his investigator-initiated randomized trial of intravenous iron in kidney transplant recipients. 0:00:00 – Episode intro & topic framing0:01:11 – Rationale & observational signals0:03:03 – Choice of primary endpoint (6‑minute walk)0:04:35 – Trial design & blinding details0:05:11 – Inclusion criteria & population profile0:07:48 – Dosing regimen & primary outcome result0:09:03 – Secondary outcomes & “fixed labs, not patients”0:12:32 – Lessons learned & future trial directions https://www.hcplive.com/view/kidney-compass-iv-iron-and-functional-outcomes-in-kidney-transplant-recipients

    17 min
  3. New 2-Year APPLAUSE-IgAN Data for Iptacopan at WCN 2026

    APR 14

    New 2-Year APPLAUSE-IgAN Data for Iptacopan at WCN 2026

    The treatment landscape for IgA nephropathy (IgAN) continues to evolve at a rapid pace, and new data presented at the World Congress of Nephrology (WCN) in Yokohama, Japan, suggest a potential shift in how clinicians approach disease modification in high-risk patients. In this episode of Kidney Compass, hosts Shikha Wadhwani, MD, MS, and Brendon Neuen, MBBS, PhD, spoke with Vlado Perkovic, MBBS, PhD, about newly presented 2-year eGFR slope data from the phase 3 APPLAUSE-IgAN trial evaluating iptacopan. 0:00:00 – Episode intro & trial topic0:00:52 – Overview of APPLAUSE trial & headline efficacy0:02:40 – Hard outcome composite & safety profile0:04:21 – Positioning iptacopan in guidelines & background therapy0:05:10 – Consistency across subgroups & need for biomarkers0:07:37 – Acute vs chronic eGFR slope with immunologic therapies0:11:29 – Rationale for combination immunologic therapy0:13:01 – Magnitude of effect, residual risk & early diagnosis https://www.hcplive.com/view/kidney-compass-new-2-year-applause-igan-data-for-iptacopan-at-wcn-2026

    20 min
  4. ASSIST Trial Shows Atrasentan Benefit on Top of SGLT2 Inhibitors

    APR 14

    ASSIST Trial Shows Atrasentan Benefit on Top of SGLT2 Inhibitors

    As the treatment landscape for IgA nephropathy grows increasingly complex, new data presented at the World Congress of Nephrology 2026 in Yokohama, Japan, are beginning to clarify how emerging therapies may work together. In this episode of Kidney Compass, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, sat down with Hiddo Heerspink, PhD, PharmD, to discuss the phase 2 ASSIST trial, which evaluated the efficacy and safety of atrasentan in combination with SGLT2 inhibitors. 0:00:00 – Episode introduction & trial focus0:00:40 – Rationale & design of ASSIST0:02:04 – Detailed crossover structure0:02:59 – Inclusion of lower proteinuria patients0:04:20 – Relationship to ALIGN trial0:05:42 – Main efficacy & safety findings0:08:43 – Role of crossover studies & individual response0:10:37 – Future sequencing of therapies https://www.hcplive.com/view/kidney-compass-assist-trial-shows-atrasentan-benefit-on-top-of-sglt2-inhibitors

    12 min

  5. 12/13/2025

    Phase 3 Data on Telitacicept in IgA Nephropathy at ASN Kidney Week 2025

    New phase 3 data released by Vor Bio underscore the potential of telitacicept, a dual BLyS/APRIL inhibitor, as a disease-modifying therapy for IgA nephropathy (IgAN), particularly for patients at high risk of progression.In this special edition episode of Kidney Compass: Navigating Clinical Trials, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS sit down with study investigators Jicheng Lv, MD, PhD, and Hong Zhang, MD, PhD, professors of internal medicine at Peking University First Hospital, following their presentation at the American Society of Nephrology (ASN) Kidney Week 2025.Telitacicept is a recombinant fusion protein designed to neutralize BLyS and APRIL, upstream drivers of B-cell survival and immunoglobulin class switching, including production of galactose-deficient IgA1, the pathogenic hallmark of IgAN. The 39-week multicenter, randomized, double-blind trial evaluated the agent’s impact on proteinuria, B-cell activity, immunoglobulin levels, and kidney function.In stage A, adults were randomly assigned 1:1 to telitacicept 240 mg subcutaneous weekly or placebo, in addition to background supportive care. The primary endpoint, which was defined as change in 24-hour urine protein-to-creatinine ratio (UPCR), was met with a −58.9% reduction in the telitacicept arm compared with −8.8% with placebo (P .0001). Week-39 data were consistent, with the treatment group showing a 55% 24-hour UPCR reduction.Clinically meaningful thresholds associated with improved long-term renal outcomes were achieved at substantially higher rates with telitacicept: 24h-UPCR 0.8 g/g: 61% vs 19.5% (placebo) 0.5 g/g: 42.1% vs 7.5% 0.3 g/g: 24.5% vs 0.6% Investigators highlighted kidney function remained stable across secondary endpoints. Mean eGFR change at week 39 was essentially unchanged with telitacicept (−0.010 mL/min/1.73 m²) compared with a modest decline in the placebo group (−0.77 mL/min/1.73 m²). Investigators also observed a lower risk of ≥30% eGFR decline (27%) with telitacicept versus placebo.Editor's Note: LV reports relevant disclosures with Chinook Therapeutics, KBP Bioscience, and others. Zhang reports no relevant disclosures.References: Lv, J, Liu LJ, Wang W, et al. Efficacy and Safety of Telitacicept in Patients with IgAN: Results from Stage A of a Phase 3 Clinical Study. Journal of the American Society of Nephrology. Telitacicept Achieved Primary Endpoint in Phase 3 Clinical Study for IgA Nephropathy | Vor Bio. Vor Bio. Published 2025. https://ir.vorbio.com/news-releases/news-release-details/telitacicept-achieved-primary-endpoint-phase-3-clinical-study-0

    18 min
  6. Understanding Renal Outcomes in SURPASS-CVOT, With Sophia Zoungas, MBBS, PhD

    11/13/2025

    Understanding Renal Outcomes in SURPASS-CVOT, With Sophia Zoungas, MBBS, PhD

    Welcome to Kidney Compass: Navigating Clinical Trials!In this special edition episode of Kidney Compass: Navigating Clinical Trials, host Brendon Neuen, MBBS, PhD, is joined by Sophia Zoungas, MBBS, PhD, an endocrinologist and head of the School of Public Health and Preventive Medicine at Monash University, to discuss a post hoc analysis of the phase 3 SURPASS-CVOT trial from American Society of Nephrology (ASN) Kidney Week 2025, which concluded tirzepatide (Mounjaro) significantly slowed kidney function decline and reduced albuminuria progression compared with dulaglutide (Trulicity) in patients with type 2 diabetes, atherosclerotic cardiovascular disease (ASCVD), and very high-risk chronic kidney disease (CKD).The analysis applied the KDIGO 2025 CKD risk classification, defining very high-risk CKD as eGFR 30 mL/min/1.73 m², or eGFR 30 to 45 mL/min/1.73 m² with micro/macroalbuminuria, or eGFR 45 to 60 mL/min/1.73 m² with macroalbuminuria.Among 1241 patients meeting these criteria, the mean age was 68.5 years, mean body mass index (BMI) was 33.0 kg/m², mean HbA1c was 8.5%, and mean diabetes duration was 19.2 years. SGLT2 inhibitor use at baseline was 24.9%.At 36 months, tirzepatide was associated with a significantly smaller decline in eGFR compared to dulaglutide: Change in eGFR: −3.0 (±0.5) mL/min/1.73 m² with tirzepatide vs −7.2 (±0.4) with dulaglutide (between-group difference: +4.1 mL/min/1.73 m²; P .001).Reductions in urinary albumin-to-creatinine ratio (UACR) also favored tirzepatide: Percent change in UACR: −45.6% with tirzepatide vs −28.0% with dulaglutide (between-group difference: −24.6%; P .001).The risk of the composite kidney outcome, which was defined as onset of macroalbuminuria, ≥50% eGFR decline, kidney failure, or kidney-related death, was 33% lower with tirzepatide (hazard ratio [HR], 0.67; 95% CI, 0.52 to 0.87; P = .002). Event rates were 16.7% (108/647) with tirzepatide and 23.0% (137/594) with dulaglutide. No new safety concerns were identified, and benefits were consistent regardless of baseline SGLT2 inhibitor use.Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Zoungas include AstraZeneca, Boehringer Ingelheim, CSL Seqirus, Eli Lilly Australia, Moderna, MSD Australia, Sanofi and Novo Nordisk.References: Zoungas S, Nicholls S, Miller DL, Nishiyama H, Wiese RJ, D’Alessio DA. Tirzepatide vs. Dulaglutide Is Associated with Reduced Major Kidney Events in Patients with Type 2 Diabetes, CVD, and Very High-Risk Kidney Diseases. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025. Eli Lilly and Company. Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefit in patients with type 2 diabetes and heart disease. July 31, 2025. Accessed July 31, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

    17 min

  7. 11/08/2025

    Setanaxib, Alport Syndrome, and RaDaR Updates at Kidney Week 2025, With Danny Gale, MB BChir, PhD

    In this special edition episode of Kidney Compass: Navigating Clinical Trials, host Brendon Neuen, MBBS, PhD sits down with Daniel Gale, PhD, MB BChir, is the director of the UK-based RaDaR Registry and the St Peter's Chair of Nephrology at University College London, at the American Society of Nephrology (ASN) Kidney Week 2025 to discuss a phase 2 trial of setanaxib in Alport syndrome and the unmet need within the disease.Interim results from the phase 2a clinical trial suggest setanaxib, a novel enzyme-driven hydrogen peroxide–depleting agent with antifibrotic properties, was safe and associated with trends toward reduced proteinuria in patients with Alport syndrome at risk for disease progression despite optimized background therapy.Alport syndrome, a rare hereditary kidney disease caused by collagen IV gene abnormalities, leads to interstitial fibrosis and progressive loss of kidney function. Gale explained targeting fibrotic pathways has been proposed as a potential strategy to slow disease progression.The 24-week, randomized, double-blind, placebo-controlled trial enrolled 20 patients aged 12–40 years with genetically confirmed Alport syndrome (AS), urine protein-to-creatinine ratio (UPCR) ≥0.8 g/g, and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m². Participants were randomized 2:1 to receive oral setanaxib (800 mg twice daily for adults 18–40 years; 800 mg + 400 mg daily for adolescents 12–17 years; n = 13) or placebo (n = 7), in addition to stable background therapy, for 24 weeks, followed by a 4-week off-treatment observation period.Most participants were receiving renin–angiotensin–aldosterone system inhibition and/or SGLT2 inhibitors: 16 were on ACE inhibitors (11 setanaxib, 5 placebo), 11 on SGLT2 inhibitors (7 setanaxib, 4 placebo), and 10 on both (7 setanaxib, 3 placebo).Primary endpoints of safety and tolerability were met. One patient in the setanaxib group experienced a serious adverse event of acute cholecystitis, deemed unrelated to treatment, and no adverse events of special interest occurred. The overall adverse event rate was similar between groups.Regarding efficacy, the setanaxib group experienced a 15% mean reduction in UPCR at week 24 versus placebo. Two patients (15.4%) achieved ≥25% reduction in UPCR, and 5 (38.5%) achieved ≥10% reduction compared with 1 (16.7%) in the placebo arm. Of note,, a 27% mean UPCR reduction was observed 4 weeks after treatment discontinuation, suggesting a sustained pharmacodynamic effect.Shifting to RaDaR registry updates, Gale highlights work evaluating C3 staining on biopsy in more than 500 patients with IgA nephropathy. Independent of proteinuria and eGFR, C3 positivity strongly predicted both eGFR decline and kidney failure, reinforcing the relevance of complement activation. The team also developed a large language model capable of reliably assigning MEST-C scores, performing comparably to expert pathologists. This innovation opens the door to analyzing the >10,000 biopsies across RADAR at scale.Gale discusses new findings on post-transplant recurrence across glomerular diseases. Patients with recurrent conditions such as nephrotic syndrome, C3 glomerulopathy, and Alport syndrome experience significantly earlier graft loss and higher lifetime transplant needs. Proteinuria ≥0.5 g/day at one year post-transplant was associated with >4-fold higher graft failure risk—underscoring an important, actionable prognostic marker.Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Gale include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.References:Gale D. Safety and Preliminary Efficacy Findings from a Phase 2A Randomized, Double- Blind, Placebo-Controlled Trial of Setanaxib in Patients with Alport Syndrome. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.Wong K, Pitcher D, Rogers DJ, Gale D. Urine Albumin-to-Creatinine Ratio and Protein-to-Creatinine to Predict Kidney Failure Rates in Patients with Glomerular and Nonglomerular Diseases in the UK National Registry of Rare Kidney Diseases (RaDaR) Cohort. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

    12 min

  8. 11/08/2025

    Obinutuzumab, REGENCY, & Updates in Lupus Nephritis, With Brad Rovin, MD

    In this special edition episode of Kidney Compass: Navigating Clinical Trials, host Shikha Wadhwani, MD, MS, sits down with Brad Rovin, MD, Lee A. Hebert Distinguished Professor of Nephrology at The Ohio State University Wexner Medical Center, to discuss updates in lupus nephritis at the American Society of Nephrology (ASN) Kidney Week 2025, including a late-breaking analysis of the phase 3 REGENCY trial.Building on the phase 2 NOBILITY signal and addressing lessons from the negative LUNAR rituximab study, where depth of B-cell depletion predicted response, REGENCY is the first successful phase 3 anti-CD20 trial in LN, showing a higher complete renal response (CRR) with obinutuzumab. The phase 3 trial randomized adults with active LN to obinutuzumab (Gazyva) plus standard therapy, which was defined as mycophenolate mofetil (MMF) and glucocorticoids, or placebo plus standard therapy. At week 76, obinutuzumab significantly increased rates of CRR compared with placebo (46.4% vs 33.1%; adjusted difference 13.4%; 95% CI, 2.0–24.8; P = .0232), leading to its FDA approval for lupus nephritis in October 2025.In a prespecified histologic substudy, 64 participants underwent paired baseline and post-week 76 kidney biopsies, and 29 provided additional tissue for B-cell and plasma cell analyses via a novel 5-plex immunofluorescence assay (CD79a, CD19, CD38, CD138, Ki67).Histologic remission (activity index [AI]=0) and near-histologic remission (AI≤1) were achieved in 46.9% and 65.6% of obinutuzumab-treated patients versus 18.8% and 21.9% with placebo (adjusted differences 30.75% and 47.69%; P = .0111 and P = .0002, respectively). The mean reduction in AI was –5.0 (SD 4.7) for obinutuzumab versus –1.8 (SD 4.6) for placebo, while chronicity index changes were minimal in both arms.Notably, more than half of obinutuzumab-treated patients who did not achieve clinical CRR still achieved histologic remission (AI=0), with a rate of 52.6% versus 8.3% among non-responders (adjusted difference 44.9%; P=0.0018), which Rovin suggests is indicative of clinical endpoints underestimating tissue-level improvement.Tissue-level biomarker data confirmed near-complete renal B-cell depletion with obinutuzumab (median change –98.3% from baseline), compared to a +29.8% increase with placebo. Plasma cell counts declined by 57.1% with obinutuzumab versus a +2.7% increase in the placebo arm, confirming deep immunologic inactivation within the kidney.Relevant disclosures for Wadhwani include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Relevant disclosures for Rovin include Alexion, Artiva, AstraZeneca/MedImmune, Aurinia Pharmaceuticals, Biogen Idec, Bristol Myers Squibb, Calliditas Therapeutics, Genentech/Hoffmann-La Roche, GSK, Omeros, Travere Therapeutics, and others.References: Rovin B. Beyond Clinical Response in the REGENCY Trial: The Impact of Obinutuzumab on Histologic Remission in Patients with Active Lupus Nephritis. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025. Genentech. FDA Approves Genentech’s Gazyva for the Treatment of Lupus Nephritis. October 20, 2025. Accessed October 20, 2025. https://www.businesswire.com/news/home/20251019548091/en/FDA-Approves-Genentechs-Gazyva-for-the-Treatment-of-Lupus-Nephritis

    32 min
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Hosted by Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, Kidney Compass: Navigating Clinical Trials is a regular podcast exploring and breaking down the latest updates and nuances of clinical trials in nephrology. By listening to Kidney Compass, you'll get the guidance you need to navigate the changing landscape of clinical trials across the spectrum of kidney disease.

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