ERA 2025 Late-Breaking Trials Preview

The 62nd European Renal Association (ERA 2025) Congress looks to continue the ongoing momentum seen in nephrology. At ERA 2024, the field welcomed the landmark FLOW trial and this year, the field is once again entering the meeting with expectations they could witness practice-changing advancements.

As part of ERA 2025, the conference is hosting a pair of late-breaking research sessions featuring pivotal readouts, new therapeutic angles, and high-level discussion with the field’s top investigators. Included in this year’s agenda are a pair of late-breaking sessions containing a combined 7 presentations on chronic kidney disease, dialysis patients, and developments in glomerular disease.

Check out our overview of the 7 studies being presented during late-breaking clinical trial sessions at ERA 2025 and our Q&A with HCPLive Nephrology advisory board member Brendon Neuen, MBBS, PhD, a senior research fellow with the George Institute for Global Health and director of the Kidney Trials Unit with Royal North Shore Hospital.

ERA Late-Breaking Clinical Trials Session 1

1. MK-2060 for Preventing Arteriovenous Graft Thrombosis in Hemodialysis Patients

Presentation: Thursday, June 05, 2025, from 11:15 to 11:40 CEST
Presenter: Wolfgang Winkelmayer, MD, MPH, of Baylor College of Medicine)

Summary:
AV graft thrombosis is a common complication in hemodialysis, leading to access failure and repeated interventions. MK-2060, a novel factor XI inhibitor, is being investigated for its antithrombotic efficacy with a potentially lower bleeding risk. This phase 2b trial evaluates whether MK-2060 can prevent graft thrombosis in chronic dialysis patients without compromising safety.

2. The CONFIDENCE Trial: Efficacy/Safety of Combining Finerenone with Empagliflozin in CKD and Type 2 Diabetes

Presentation: Thursday, June 05, 2025, from 11:40 to 12:05 CEST
Presenter: Rajiv Agarwal, MD (Indiana University & VA Medical Center)

Summary:
Both SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce kidney and cardiovascular risks in patients with diabetic CKD, but their combined use is not well studied. The CONFIDENCE trial evaluates whether combining finerenone and empagliflozin offers additive kidney protection and cardiovascular benefits, with a focus on safety, especially around hyperkalemia and volume status.

3. Exploring the Margins of Survival Benefit in Deceased Donor Kidney Transplantation: An International Target Trial Emulation

Presentation: Thursday, June 05, 2025, from 12:05 to 12:30 CEST
Presenter: Rachel Hellemans, MD (Antwerp University Hospital)

Summary:
Although deceased donor kidney transplantation improves survival over dialysis, benefits vary across patient populations. This international study uses target trial emulation methods to estimate the survival advantage in different subgroups, helping to refine transplant candidacy criteria and inform shared decision-making.

ERA Late-Breaking Clinical Trials Session 2

1. Sibeprenlimab for Patients with IgA Nephropathy: Prespecified Interim Analysis of the Phase 3 VISIONARY Study

Presentation: Friday, 6 June | 11:15–11:33 CEST
Presenter: Vlado Perkovic, MBBS, PhD, of George Institute for Global Health

Summary:
Sibeprenlimab, a monoclonal antibody targeting APRIL, aims to reduce pathogenic IgA production in IgA nephropathy. The VISIONARY trial is a global phase 3 study evaluating whether sibeprenlimab slows kidney function decline. This interim analysis reports efficacy and safety data in patients with biopsy-confirmed IgAN and persistent proteinuria despite standard care.

2. Impact of Acute eGFR Dips and Markers of Disease Severity on Effects of Empagliflozin on Acute Kidney Outcome

Presentation: Friday, June 06, 2025, from 11:33 to 11:51 CEST
Presenter: Natalie Staplin, PhD, ofthe University of Oxford

Summary:
SGLT2 inhibitors commonly cause early eGFR dips, which are often reversible and non-pathologic. This analysis examines whether the magnitude of the eGFR dip, along with baseline disease severity, influences longer-term kidney outcomes in patients taking empagliflozin, helping clinicians interpret initial renal function changes during therapy.

3. Spironolactone in Patients Undergoing Maintenance Dialysis: The ACHIEVE Trial

Presentation: Friday, June 06, 2025, from 11:51 to 12:09 CEST
Presenter: Michael Walsh, MD, PhD, of McMaster University

Summary:
Spironolactone has shown cardiovascular benefit in earlier-stage CKD, but its role in dialysis patients is unclear due to concerns about hyperkalemia. The ACHIEVE trial evaluates whether spironolactone improves cardiovascular outcomes in dialysis patients, with a focus on safety and efficacy in this high-risk group.

4. Mineralocorticoid Receptor Antagonists in Kidney Failure Receiving Dialysis: An Updated Systematic Review and Meta-analysis

Presentation: Friday, June 06, 2025, from 12:09 to 12:27 CEST
Presenter: Lonnie Pyne, MD, of McMaster University

Summary:
Building on trials like ACHIEVE, ALCHEMIST, and others, this updated meta-analysis synthesizes recent evidence on MRAs in dialysis patients. It assesses effects on cardiovascular mortality, hospitalization, and adverse events—particularly hyperkalemia—providing a clearer picture of the risk–benefit profile of MRAs in end-stage kidney disease.

Q&A on ERA 2025 Trials to Watch, with Brendon Neuen, MBBS, PhD

HCPLive: After a historic ERA 2024, what are you looking forward to most from ERA 2025?

Brendon Neuen MBBS, PhD: I think last year was a fantastic meeting in Stockholm with a lot of practice-changing science. And I think we can expect a similar theme from this year's meeting in Vienna, there's some really important trial data that are being presented—studies like the CONFIDENCE trial, studies like ACHIEVE looking at Spironolactone in end stage kidney disease, as well as sibeprenlimab, an APRIL inhibitor, in the VISIONARY trial in IgA nephropathy. So, really important new clinical trial updates.

Aside from that, ERA is always a great meeting with lots of great debates on important clinical topics in nephrology, like genetic testing and kidney disease use of plasma exchange and important and controversial topics, and of course, a lot of new updates across the spectrum of kidney diseases, from IGA nephropathy to ultra rare diseases like C3 glomerulopathy, and, of course, new insights from trials in diabetic kidney disease with agents such as finerenone and empagliflozin. So overall, I think a really interesting and broad but also in-depth program at era that I'm really looking forward to.

HCPLive: Can you explain why the CONFIDENCE trial is on your shortlist of trials to watch from ERA 2025?

Brendon Neuen MBBS, PhD: I am really excited about CONFIDENCE. We are now in an era of multiple highly effective therapies for diabetic kidney disease with SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone, but we don't yet have a lot of direct randomized evidence about how to use these medications in combination, and importantly, initiate them simultaneously. This is important because we know that there are potential gaps in implementation and treatment inertia with using multiple medicines. The CONFIDENCE trial seeks to address that evidence gap about combination therapy. It's enrolling about 800 patients with type 2 diabetes and chronic kidney disease, with an EGFR greater than 30 milliliters per minute and at least a UACR of 100 milligrams per gram, and randomizing them to empagliflozin and finerenone or combined simultaneous initiation with a primary outcome of change in albuminuria at 6 months. And I think what is really important about this trial is it will give us direct randomized evidence not only about the efficacy of simultaneous initiation in CKD of these 2 classes of agents, but importantly, safety data, and that is the kind of information that is really critical to nephrology practice if we are going to implement these therapies in a way that is being tested, such as in the CONFIDENCE trial.

HCPLive: Can you provide background on the ACHIEVE trial and why you have included it in your trials to watch for ERA 2025?

Brendon Neuen MBBS, PhD: Well, we're really witnessing a renaissance in interest in mineralocorticoid biology and aldosterone in general, with so many new agents targeting this pathway, from nonsteroidal MRAs like finerenone to new agents like aldosterone synthase inhibitors being tested, not only in kidney disease, but for heart failure and for heart failure prevention. Now, there has always been very limited evidence for the use of MRAs in patients with advanced CKD, particularly those with kidney failure on dialysis, and this is important because this population is at extremely high risk of cardiovascular disease, an extremely high risk of heart failure, hospitalization, yet there is the fewest data available. The ACHIEVE trial is the largest international, multicenter trial that has been conducted evaluating the effect of an MRA, in this case, spironolactone versus placebo, on heart failure hospitalization or cardiovascular death in about 2000 patients with dialysis-dependent kidney failure.

A few years ago, there was a French study called ALCHEMIST evaluating spironolactone in dialysis. That trial was overall neutral in terms of the primary cardiovascular outcome, but suggested potential benefits on heart failure. So, these data will be really important in determining the efficacy and safety of spironolactone in end stage kidney disease on dialysis, who face not only high risk of heart failure, hospitalization and cardiovascular events, but also at the same time, high risk of adverse events like hypokalemia. So, evaluating the safety and efficacy profile of spironolactone in this population is going to be critically important, and this is the question that this trial seeks to answer.

HCPLive: With so much advancement in IgA nephropathy, what separates sibeprenlimab from other agents, either approved or in the pipeline, and how does this set the stage for VISIONARY?

Brendon Neuen MBBS, PhD: You've touched on the key issues here. That, you know, we're seeing so many new treatment options and expanding opportunities to improve outcomes for patients with IGA nephropathy, agents being approved, things like iptacopan, complement inhibition, budesonide, and also sparsentan in IgA nephropathy. But what is so interesting about sibeprenlimab is that it's an APRIL inhibitor, and it targets the underlying immunological basis of IgA nephropathy. That is, it reduces the production of galactose deficient IgA, which is important and central to the pathogenesis the development and progression of IgA nephropathy.

There are data from earlier phase studies of APRIL inhibitors that demonstrate that this class of agent substantially reduces proteinuria and albuminuria in people with IgA nephropathy, but we don't have long term outcomes yet, and we don't have phase 3 data. This trial is enrolling about 500 people with biopsy-proven IgA nephropathy who are at high risk of progression, all patients are on RAAS blockade, and almost half of patients also on an SGLT2 inhibitor. So, this is going to provide really important information on albuminuria, lowering effects, and also in longer term effects on GFR slope, which won't be presented, of course, at this meeting, but will also be presented in the longer term.