Brendon Neuen, MBBS, PhD

Hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, welcome Dana Rizk, MD, professor of medicine in the Division of Nephrology at the University of Alabama at Birmingham. Rizk walks through the 24-month eGFR and safety findings from the phase 3 VISIONARY trial of sibeprenlimab (Voyxact) in 

She presented the late-breaking results at GlomCon Hawaii 2026, building on the proteinuria data reported earlier this year at the European Renal Association meeting. The conversation covers trial design, the eGFR slope and change-from-baseline outcomes, subgroup consistency, safety, and where residual proteinuria fits into the picture going forward.

Kidney Compass: VISIONARY 2-Year eGFR Data in IgA Nephropathy

VISIONARY Trial Design and 2-Year eGFR Results in Sibeprenlimab-Treated IgAN

Wadhwani opens by asking Rizk to set the scene, noting VISIONARY enrolled 510 patients with biopsy-proven, high-risk IgAN, making it the largest phase 3 trial in the disease to date. Rizk describes the eligibility criteria, an eGFR > 30, a recent biopsy for patients on the lower end, and significant proteinuria of ≥ 1 g/day. Patients were randomized to sibeprenlimab 400 mg subcutaneously every 4 weeks or placebo, on top of maximum tolerated RAS inhibition. 

Rizk explains sibeprenlimab targets APRIL, a cytokine driving B cells to become IgA-secreting within the four-hit model of IgAN pathogenesis, and Wadhwani calls the mechanism one of the most exciting new directions in the field.

Neuen reminds listeners the earlier phase 2 signal was compelling but short, often under a year, and asks Rizk for the full picture now the trial has matured. Rizk reports an annualized eGFR slope of 0.3 mL/min/1.73 m² per year with sibeprenlimab against a placebo decline of 4.2, a 4.5 mL/min/1.73 m² per year treatment difference. Mean eGFR change from baseline told a similar story, with a 9.2 mL/min gap between arms at 2 years. Rizk calls the result striking against the 2025 KDIGO goal of holding eGFR loss < 1 mL/min per year, a bar she once doubted was achievable within a 2-year window.

Consistent Subgroup Benefit and Reassuring Safety Data From VISIONARY

Rizk noted a trio of prespecified subgroups, defined by proteinuria level, baseline eGFR, and SGLT2 inhibitor use, all favored sibeprenlimab with no meaningful difference in effect size across strata. Neuen called the consistent benefit in SGLT2 inhibitor users reassuring for clinicians considering combination therapy for long-term kidney preservation.

On safety, Neuen names the theoretical concern hanging over any B-cell modulating agent: infection risk from suppressing immune function. Rizk reports adverse events in about 90% of both arms, with treatment-related events similar between groups and serious infections less common with sibeprenlimab than placebo. No deaths occurred, and discontinuation for adverse events stayed in the low single digits. Wadhwani follows up on immunoglobulin monitoring, and Rizk notes patients needed an IgG level > 600 at entry, with full IgA, IgG, and IgM data still to come.

Residual Proteinuria and the Road Ahead for B-Cell Therapy in IgAN

With median proteinuria still > 0.5 gram/day despite the 51% reduction, Wadhwani raised concern about residual proteinuria as a cardiovascular risk factor independent of stabilized eGFR. She compared it to how cardiologists treat persistent albuminuria. Rizk agreed proteinuria cannot distinguish ongoing immunologic activity from fixed scarring, and said mechanistic studies pairing biopsies before and after treatment should help clarify the distinction. 

The conversation closes on biomarkers, with Wadhwani asking whether galactose-deficient IgA1 can separate disease activity from fibrosis on its own. Rizk says the field has been spoiled by the PLA2R antibody in membranous nephropathy and expects IgAN will need a panel of biomarkers rather than one perfect test. She points to pediatric IgAN, membranous nephropathy, lupus nephritis, and IgA vasculitis as likely next frontiers for anti-APRIL therapy. 

Wadhwani adds trials still struggle to capture good hematuria data given how urine samples are collected. Rizk says post hoc analyses are planned for patients enrolled with lower baseline proteinuria, thanking the patients and investigators who carried VISIONARY through its multi-year follow-up.

Wadhwani closes by reflecting on how far the field has moved. A decade ago, clinicians reserved corticosteroids for patients with more than a gram of proteinuria after months of failed RAS inhibition, often leaving patients undertreated given the steroid burden. She contrasts this with a once-monthly injection appearing well tolerated and capable of stabilizing kidney function outright. Rizk also raises a question about whether anti-APRIL therapy has a role preventing IgAN recurrence after kidney transplant, calling it an open area for future study. 

 include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Disclosures for 

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

 include Novartis Pharmaceuticals, Otsuka Pharmaceutical Inc., Vera Therapeutics, Biogen, Travere Therapeutics, and others.

Perkovic V, Trimarchi H, Tesar V, et al. Sibeprenlimab in IgA nephropathy: interim analysis of a phase 3 trial. 

. 2026;394(7):635-646. doi:10.1056/NEJMoa2512133

Otsuka. Otsuka unveils unprecedented phase 3 VISIONARY two-year eGFR results demonstrating VOYXACT (sibeprenlimab-szsi) stabilizes kidney function decline to baseline physiologic rate, fundamentally altering disease progression in IgA nephropathy (IgAN). News release. August 3, 2026. 

https://www.otsuka-us.com/news/otsuka-unveils-unprecedented-phase-3-visionary-two-year-egfr-results-demonstrating-voyxactr

Rizk DV, Perkovic V, Trimarchi H, et al. Two-year eGFR and safety results from the VISIONARY phase 3 trial of sibeprenlimab in IgA nephropathy. Presented at: GlomCon Hawaii; August 3-7, 2026; Maui, HI.

Podcasts

Dana Rizk, MD, joins hosts Brendon Neuen and Shikha Wadhwani to unpack 2-year VISIONARY data showing sibeprenlimab stabilizes eGFR in IgAN.

Kidney Compass: Rituximab Cuts Relapse Risk in MCD, FSGS in TURING Trial

Congress in Glasgow, Scotland, results from the TURING trial offered long-awaited evidence that rituximab can meaningfully reduce relapse rates in adults with minimal change disease (MCD) and

 focal segmental glomerulosclerosis (FSGS)

These conditions have been historically managed with prolonged, high-dose corticosteroid courses, carrying a substantial burden of adverse effects. In this episode of 

, host Brendon Neuen, MBBS, PhD, spoke with Lisa Willcocks, MBBChir, MRCP, PhD, a consultant nephrologist who leads the primary glomerular disease service at Addenbrooke's Hospital in Cambridge, United Kingdom, about the trial she presented as a late-breaking clinical result at the congress.

"Rituximab is now so much cheaper than it used to be," Willcocks said. "Hopefully, this is a drug that will be available to people worldwide and will spare the burden of steroids that patients have been exposed to."

Indication: Relapsing/de novo MCD and FSGS in adults

Trial: Turing (phase 3, randomized, placebo-controlled)

Key result: >50% reduction in relapse rate vs placebo

Safety: No increase in adverse events vs placebo

Why Rituximab Was Evaluated in Adult Nephrotic Syndrome

The rationale for the TURING trial stems from a well-recognized clinical challenge: although most adults with MCD and FSGS respond initially to corticosteroids, the majority will relapse. Standard of care, as outlined by KDIGO guidelines, calls for prednisolone at 1 mg/kg per day, capped at 80 mg, followed by a slow taper over six months. In patients who relapse, this cycle repeats, meaning individuals with frequently relapsing disease accumulate substantial cumulative steroid exposure over years, often beginning in early adulthood.

Turing Trial Design: Population, Randomization, and Steroid Weaning Stratification

The TURING trial randomized 149 adults in a 1:1 ratio to either rituximab or placebo. Rituximab was administered as two 1 g doses given 1 to 3 weeks apart, initiated within 4 weeks of starting corticosteroid treatment for nephrotic syndrome. Patients who remained in remission at 6 months received a third dose of their assigned treatment. In the placebo arm, participants who relapsed were unblinded and offered open-label rituximab, providing an additional dataset on delayed treatment initiation.

The trial population had a median age in the early 50s, with approximately 70% identifying as White British, reflective of the UK referral base. 38% of participants had FSGS, while the remainder had MCD. Additionally, approximately one-third had de novo disease and two-thirds had relapsing disease at enrollment.

An important design feature was stratification by steroid tapering regimen. Clinicians were permitted to choose either the standard KDIGO taper or a faster wean, the latter reducing total prednisolone exposure by approximately 1 gram, allowing the trial to assess whether the rituximab effect held regardless of steroid management strategy.

What the Phase 3 Trial Showed: Relapse Rates, Disease Subgroups, and Duration of Remission

The primary endpoint was time from remission to relapse, assessed over a median follow-up of 2.8 years, with some participants followed for up to 4 to 5 years. In the placebo group, the median time to relapse was under 6 months. In the rituximab group, the median time to relapse was not reached during the follow-up period, meaning more than half of treated patients remained in remission at study close. Overall, rituximab was associated with a greater than 50% reduction in relapse rate compared with placebo.

Willcocks reported consistent effects across MCD and FSGS subgroups. In patients with relapsing disease, results were statistically significant; in those with de novo disease, the odds ratios were similar in direction and magnitude, but the confidence interval crossed zero, likely reflecting the smaller sample size in that stratum, approximately 50% of de novo placebo patients relapsed compared with approximately 22% in the de novo rituximab group. Notably, the benefit of rituximab was preserved regardless of which steroid tapering schedule was used, supporting the possibility that a faster, less toxic steroid wean can be combined with rituximab without compromising efficacy.

In the open-label phase, patients from the placebo arm who subsequently received rituximab after relapse showed Kaplan-Meier curves nearly identical to those of the primary rituximab group, underscoring the consistency and reproducibility of the effect.

Safety Findings Reported With Rituximab in the Turing Trial

Adverse event rates were similar between the rituximab and placebo groups, and no new safety signals emerged in the open-label treatment phase. Wilcox noted that although participants frequently entered the trial with hypogammaglobulinemia secondary to nephrotic syndrome, IgG levels improved as patients achieved remission, and no cases of treatment-emergent hypogammaglobulinemia were identified during the trial period. B-cell monitoring via CD19 levels was not performed systematically, partly to preserve blinding and partly because existing literature suggests limited utility in predicting relapse timing.

Unanswered Questions: Redosing Timing, Biomarkers, and Long-Term Use

Several clinically relevant questions remain open following the Turing trial. Willcocks acknowledged that the trial did not establish an optimal redosing interval for rituximab in patients who achieve sustained remission. Based on her clinical experience following the trial, she described a general approach of administering 2 initial doses followed by a 6-month dose and then monitoring for relapse, noting that most patients in the trial remained in remission for approximately two to three years from the time of initial treatment. Whether an annual maintenance dose would be sufficient to sustain remission for a broader population, and how to individualize that decision, were flagged as priorities for future investigation.

The role of anti-nephrin antibodies, a biomarker not yet available when the trial was designed, was also identified as an emerging area of interest, with Wilcox suggesting it may eventually inform relapse prediction. The trial's investigator-initiated design limited some ancillary biomarker collection, though a large dataset has been assembled, and the investigators indicated openness to collaborative analyses.

Editor’s Note: Willcocks reports relevant disclosures with Chemocentryx, Rigel, Novartis, GSK, and others.

Willcocks L. TURING trial: rituximab in adults with minimal change disease and FSGS. Presented at: European Renal Association Congress; Glasgow, Scotland; 2025.

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. 

Ravani P, Magnasco A, Edefonti A, et al. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. 

 2011;6(6):1308-1315. doi:10.2215/CJN.09421010

Rovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. 

The phase 3 TURING trial found rituximab slashed relapse rates in adults with minimal change disease and FSGS, offering a steroid-sparing alternative.


Kidney Compass: 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 

, 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.

As Cherney explained during the discussion, REMODEL was conceived as a companion to the landmark FLOW trial, which demonstrated significant reductions in cardiorenal outcomes with semaglutide. While FLOW established clinical efficacy, Cherney emphasized that REMODEL was designed to answer a different question: why these benefits occur. Both he and Neuen highlighted that prior analyses suggested the observed kidney protection could not be fully explained by traditional risk factor improvements such as glycemic control, weight loss, or blood pressure reduction.

To address this, Cherney described how REMODEL incorporated a range of advanced imaging and biomarker-based endpoints. The primary outcome focused on MRI-derived measures of kidney oxygenation, while secondary endpoints included albuminuria, kidney function, and a suite of mechanistic markers such as fibrosis, intrarenal fat, and inflammatory pathways. A subset of participants also underwent paired kidney biopsies, allowing for direct assessment of cellular and molecular changes within the kidney.

According to Cherney, the trial did not demonstrate an effect on kidney oxygenation, but did reveal several other important mechanistic signals. He noted that semaglutide led to a reduction in perirenal and hilar fat, a finding that Neuen highlighted as particularly intriguing given emerging hypotheses around the role of local adiposity in kidney injury. Cherney also pointed to improvements in markers of fibrosis and inflammation, including changes in endothelial cell biology and reductions in inflammatory cell populations, suggesting a direct intrarenal effect.

The conversation explored these findings in greater depth, with Neuen raising the possibility that perirenal fat may contribute to kidney injury through both mechanical and inflammatory mechanisms. In response, Cherney outlined multiple potential pathways, including physical compression of renal structures and the metabolic activity of adipose tissue driving cytokine-mediated injury. Both emphasized that these hypotheses warrant further investigation but may represent an underappreciated contributor to disease progression.

Clinically, Cherney reported that semaglutide reduced albuminuria by approximately 40%, reinforcing its potential as a kidney-protective therapy. He also presented subgroup analyses from the REMODEL trial showing consistent effects regardless of baseline use of SGLT2 inhibitors. Neuen noted that this finding aligns with broader evidence suggesting additive and complementary mechanisms between these drug classes, supporting their combined use in high-risk patients.

Looking ahead, both speakers emphasized the broader implications of these findings. Cherney suggested that the mechanisms observed in REMODEL, particularly those related to inflammation and endothelial dysfunction, are likely not specific to diabetes and may extend to non-diabetic kidney disease. He also stressed the importance of reframing semaglutide as a kidney-directed therapy, independent of its effects on glucose or weight, a point Neuen reinforced as critical for both clinicians and patients.

Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for Cherney include Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Abbvie, Janssen, AMGEN, Bayer, , Gilead, CSL-Behring, Otsuka, Novartis, GSK, and others.

David Cherney, MD, PhD, discusses REMODEL trial insights into how semaglutide reduces albuminuria and impacts kidney fat and fibrosis pathways.

Kidney Compass: 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.

Throughout the conversation, de Borst emphasized that the study was motivated by a gap between clinical perception and patient experience. While kidney transplant recipients are often thought to do well, he noted that a subset of patients continue to experience reduced exercise capacity, approximately 20% lower than healthy individuals on average. At the same time, iron deficiency remains common in this population, affecting roughly 1 in 5 patients.

Drawing on prior observational work, de Borst explained that iron deficiency had been associated with worse outcomes across multiple domains, including physical function, quality of life, and cognitive performance, raising the question of whether these relationships were causal.

Neuen reinforced that iron’s biological role extends well beyond erythropoiesis, highlighting its importance in mitochondrial function and muscle performance, while Wadhwani underscored the novelty of focusing on functional endpoints rather than traditional kidney metrics. As de Borst described, the trial was designed with a primary endpoint of the 6-minute walk test, selected for its practicality and reproducibility in a multicenter setting, alongside a broad range of secondary outcomes including neurocognitive testing, quality of life assessments, and cardiac imaging.

The study enrolled 148 stable kidney transplant recipients with iron deficiency, irrespective of hemoglobin levels, and randomized them to receive intravenous ferric carboxymaltose or placebo over a 24-week period. According to de Borst, the results showed modest improvements in exercise capacity. Of note, these improvements were observed in both the treatment and placebo groups, with no significant difference between them. He further noted that secondary outcomes, including cognitive function, cardiac parameters, and quality of life, were similarly neutral.

Despite these findings, de Borst pointed out that biochemical markers of iron status improved substantially in the treatment arm, indicating that while iron stores were corrected, this did not translate into measurable clinical benefit in this population. He also highlighted a small, unexpected signal suggesting a potential improvement in kidney function, though he cautioned that this finding requires further investigation.

The discussion then turned to how these results should be interpreted. Neuen raised the possibility of a ceiling effect, noting that patients in the trial were relatively high functioning at baseline, which may have limited the ability to detect meaningful improvements. De Borst agreed, explaining that while participants had some impairment compared with predicted values, they were not as severely affected as populations in which intravenous iron has shown benefit, such as heart failure.

Looking back, de Borst reflected that selecting a more symptomatic population or one with greater baseline functional limitation may have yielded different results. Both hosts emphasized that this highlights the challenges of trial design in relatively stable transplant populations and the importance of aligning endpoints with patient characteristics.

The conversation expanded beyond the trial itself to broader implications for the field. Neuen stressed that unlike cardiology, where intravenous iron has demonstrated benefits on functional outcomes, nephrology has remained largely focused on hemoglobin-based endpoints. He and de Borst both suggested that this paradigm may need to shift, particularly in non-dialysis chronic kidney disease populations where symptom burden is high and data on patient-centered outcomes remain limited.

Wadhwani echoed this perspective, noting the growing need to better understand how therapies impact how patients feel and function, not just traditional laboratory measures.

Editors’ note: Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. De Borst reports no relevant disclosures.

Martin de Borst, MD, PhD, discusses IV iron use in transplant recipients through an RCT focused on exercise capacity, function, and quality of life.

Brendon Neuen, MBBS, PhD

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