Brendon Neuen, MD

Welcome to Kidney Compass: Navigating Clinical Trials!

Kidney Compass: Understanding Renal Outcomes in SURPASS-CVOT

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; 

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%; 

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; 

= .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.

 include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for 

include AstraZeneca, Boehringer Ingelheim, CSL Seqirus, Eli Lilly Australia, Moderna, MSD Australia, Sanofi and Novo Nordisk.

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

Podcasts

Discover groundbreaking insights from ASN Kidney Week on the SURPASS-CVOT trial.

Kidney Compass: Setanaxib, Alport Syndrome, and RaDaR Updates at Kidney Week 2025

, 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 

 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.

include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.

Safety and Preliminary Efficacy Findings from a Phase 2A Randomized, Double- Blind, Placebo-Controlled Trial of Setanaxib in Patients with Alport Syndrome. 

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. 

Neuen and Gale break down groundbreaking insights on Alport syndrome and glomerular diseases, including RaDaR registry data.

Kidney Compass: Lafayette and ORIGIN 3 at Kidney Week 2025

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Ricahrd Lafayette, MD, from the floor at the 

 evaluating atacicept and how it adds to the totality of evidence supporting the use of the dual BAFF/APRIL inhibitor in IgA nephropathy (IgAN). 

Lafayette describes the moment as “predictably exciting,” noting that the phase 3 findings strongly mirror the promising signals seen previously in the ORIGIN phase 2 program.

The phase 2 trial, which evaluated weekly atacicept dosing, demonstrated a robust biologic impact with approximate reductions of 75% in galactose-deficient IgA1 and 50% in proteinuria at 96 weeks, hematuria resolution in most affected patients, and an annual eGFR decline of only ~0.6 mL/min/1.73 m², which Lafayette noted was far below the expected trajectory in this population. These data guided the design of ORIGIN 3, which enrolled biopsy-proven IgA nephropathy with >1 g/day of proteinuria, eGFR >30 mL/min/1.73 m², and maximally tolerated background therapy. More than half of the participants were also taking an SGLT2 inhibitor. 

Lafayette reports the 9-month primary outcome results aligned closely with phase 2. Atacicept achieved >45% reductions in proteinuria, compared with approximately 7% in the placebo group. Gd-IgA1 fell by approximately 75–80%, and hematuria resolved in most atacicept-treated patients with minimal change on placebo. Lafayette highlighted these effects were consistent across prespecified subgroups, including those on SGLT2 inhibitors.

Safety findings demonstrated there was no increase in infections or serious adverse events relative to placebo, aside from mild injection-site reactions. Lafayette pointed out, numerically, severe adverse events occurred more often in the placebo arm.

While regulatory restrictions prevent release of 9-month eGFR data, Lafayette notes the close resemblance to the phase 2 trajectory supports optimism for the upcoming 2-year readout. However, he emphasizes that atacicept-related biomarker improvements reverse when treatment stops, indicating that ongoing therapy may be necessary for sustained benefit.

The discussion concludes by situating atacicept within a rapidly expanding therapeutic landscape, including other B-cell–directed agents targeting APRIL alone. Head-to-head differences remain unknown, but atacicept’s dual BAFF/APRIL inhibition and consistent efficacy across optimized background therapy make it a compelling potential addition.

 include Aurinia, Callidatas, Complexa, Mallinckrodt, Omeros, Pfizer, Vera Therapeutics, and others. Relevant disclosures for 

 include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for

include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others.

Lafayette R, Barbour SJ, Brenner RM, et al. 

ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN

. Presented at the American Society of Nephrology (ASN) Kidney Week. Houston, Texas. November 05-09, 2025.

Vera Therapeutics Announces Atacicept Achieved 46% Proteinuria Reduction in ORIGIN Phase 3 Trial in Adults with IgA Nephropathy. Vera Therapeutics, Inc. June 2, 2025. Accessed June 2, 2025. 

https://ir.veratx.com/news-releases/news-release-details/vera-therapeutics-announces-atacicept-achieved-46-proteinuria

Discover groundbreaking insights from the ORIGIN 3 study on IgA nephropathy, showcasing promising results and future treatment possibilities.

Kidney Compass: Atacicept and ORIGIN 3 at Kidney Week 2025, with Richard Lafayette, MD

Counting down the biggest news from major medical meetings, it's the HCPLive Five!

HCPLive Five at European Renal Association (ERA) Congress 2025

European Renal Association (ERA) Congress

 is a medical conference bringing together world-renowned experts, researchers, and practitioners in nephrology. ERA Congress 2025 was hosted in Vienna, Austria, and saw more than 10,000 participants from  91 countries around the world, with a record 2835 abstract submissions. This year’s conference was centered around the theme “Game Changers in Nephrology” with the slogan “Beyond Nephrology,” boasting a comprehensive and innovative program exploring the latest advancements and transformative ideas in nephrology.

As part of HCPLive’s on-site coverage, the editorial team conducted expert interviews and reported on timely topics across therapeutic advances, pipeline updates, new renal clinical trial data, and more. In this edition of the HCPLive Five, the team highlights key conversations on pegcetacoplan in 

 and idiopathic immune-complex membranoproliferative glomerulonephritis (IC-MPGN), a trio of 

 drugs in clinical development, and the potential benefits of simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with 

Pegcetacoplan Sustains Proteinuria Reductions in C3G, IC-MPGN at 52 Weeks

Extended data from the phase 3 VALIANT trial were presented at ERA 2025 and support the sustained efficacy and safety of pegcetacoplan (Empaveli) in patients with C3G or IC-MPGN, including adolescents and adults with native or transplanted kidneys. The 52-week results show continued proteinuria reduction and eGFR stabilization in both treatment-naïve and crossover groups, reinforcing 26-week data presented at the American Society of Nephrology’s 2024 Scientific Sessions.

In this on-site interview at the meeting, Fadi Fakhouri, MD, PhD, co-lead principal investigator for the VALIANT study and a professor of nephrology at CHUV Lausanne, Switzerland, describes pegcetacoplan’s long-term potential in C3G and IC-MPGN and how the data presented at ERA could shift treatment strategies.

Understanding Zigakibart's Potential in IgA Nephropathy, with Jonathan Barratt, MD, PhD

100-week data from the phase 1/2 ADU-CL-19 trial presented at ERA suggest zigakibart, an APRIL inhibitor under development by Novartis, offers durable reductions in proteinuria and maintains a favorable safety profile in patients with IgAN. In the study, patients experienced a mean 60% reduction in proteinuria from baseline, with 55% achieving proteinuria below 500 mg and 31% below 300 mg, as described by Jonathan Barratt, MD, PhD, the Mayer Professor of Renal Medicine at the University of Leicester, in this interview. Additionally, serum IgA and pathogenic Gd-IgA1 levels dropped by 74%, building on earlier 52-week data showing reductions in IgA, IgM, and IgG of 67%, 78%, and 35%, respectively.

Kidney Compass: CONFIDENCE Trial at ERA 2025, with Rajiv Agarwal, MD, MS

Simultaneous initiation of finerenone (Kerendia) and empagliflozin (Jardiance) in patients with CKD and type 2 diabetes was well-tolerated and resulted in significantly greater reductions in urinary albumin-to-creatinine ratio (UACR) than either agent alone, according to results from the CONFIDENCE trial. During ERA, Kidney Compass host Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and the director of the Kidney Trials Unit with Royal North Shore Hospital, held a discussion with trial investigators Rajiv Agarwal, MD, Professor Emeritus at Indiana University School of Medicine, about the study results and what they mean for CKD management landscape in real-world settings.

Phase 3 ORIGIN Sets Stage for Atacicept in IgA Nephropathy, with Richard Lafayette, MD

Just days before the ERA 2025, the nephrology community welcomed and celebrated new positive data for atacicept in IgAN in the form of topline results from the phase 3 ORIGIN trial. Announced by Vera Therapeutics on June 02, 2025, the data indicate the trial met its primary endpoint of reduction in proteinuria at week 36, with the atacicept group achieving a 46% reduction from baseline and a statistically significant 42% reduction compared to placebo at week 36.

’s coverage of ERA, we sat down with Lafayette to discuss how this latest data adds to our understanding of atacicept and its potential role in the management of IgAN if it were to receive FDA approval.

Kidney Compass: Sibeprenlimab and the VISIONARY Trial, with Vlado Perkovic, MBBS, PhD, at ERA 2025

, hosts Brendon Neuen, MBBS, PHD, and Shikha Wadhwani, MD, MS, are joined by Vlado Perkovic, MBBS, PhD, dean and scientia professor of Medicine at UNSW Sydney, as he dives into one of the meeting’s most anticipated releases—

. Less than 2 weeks prior to the presentation, Otsuka Pharmaceutical Co. announced the US Food and Drug Administration had granted priority review for their BLA and the application has been given a target action date of November 28, 2025.

These 5 represent only some of the data the 

 team covered at this year's meeting! Check out more KOL insight and our full conference coverage on our 

Videos

From new data for potential IgAN treatments to the use of combination initiation therapy for type 2 diabetes and CKD, here are 5 key updates from the annual meeting.

Brendon Neuen, MD

Articles