Rajiv Agarwal, MD, MS, is a Professor Emeritus of Medicine at Indiana University School of Medicine and VA Medical Centre in Indianaoplis.

Rajiv Agarwal, MD, MS

FIND-CKD Trial Poses Finerenone as a "Third Pillar" for Nondiabetic CKD

Finerenone (Kerendia), a nonsteroidal mineralocorticoid receptor antagonist (MRA) already approved for 

 slowed the rate of kidney function decline in adults with CKD who did not have diabetes, according to results of the phase 3 FIND-CKD trial published in the New England Journal of Medicine.

Rajiv Agarwal, MD, professor emeritus of medicine at Indiana University School of Medicine and staff physician at the Richard L. Roudebush VA Medical Center, frames finerenone as completing a trio of complementary mechanisms: RAS inhibitors work hemodynamically, SGLT2 inhibitors act on tubular and metabolic pathways, and finerenone targets inflammation and fibrosis. Together, he said, they may now function as 3 distinct pillars of CKD care.

 Nondiabetic CKD, phase 3 FIND-CKD (n=1584)

 22% reduction in heart failure hospitalization, 18% reduction in CV death

While you’re here, check out part 1 of our conversation with Agarwal:

https://www.hcplive.com/view/find-ckd-expands-finerenone-evidence-beyond-diabetic-ckd-with-rajiv-agarwal-md

How Much Did Finerenone Slow Kidney Decline?

Agarwal and colleagues randomly assigned 1584 adults with CKD and albuminuria who were already taking a renin–angiotensin system (RAS) inhibitor to finerenone, 10 or 20 mg daily, or placebo.

At baseline, participants had an eGFR of 25 to less than 90 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio of 200 to 3500, with a similar mean baseline eGFR between groups, at roughly 47 mL/min/1.73 m².

Over 32 months, the mean annual rate of change in eGFR, the trial's primary outcome, was −3.3 mL/min/1.73 m² with finerenone compared with −4.0 mL/min/1.73 m² with placebo, a difference of 0.7 mL/min/1.73 m² (95% CI, 0.3-1.1; 

A prespecified hierarchical analysis also showed a reduced risk of a composite kidney or cardiovascular outcome, defined as a sustained eGFR decline of at least 57%, kidney failure, heart failure hospitalization, or cardiovascular death, with finerenone versus placebo (hazard ratio, 0.77; 95% CI, 0.60-0.99; P = .04).

Does Finerenone Reduce Cardiovascular Events? What the Pooled Infinity Analysis Adds

In FIND-CKD alone, the cardiovascular composite trended favorably but did not reach statistical significance on its own (hazard ratio, 0.60; 95% CI, 0.27-1.33). A larger pooled analysis, Infinity, combining FIND-CKD with finerenone's prior diabetic CKD trials, filled in that picture: heart failure hospitalization and cardiovascular death were each independently, statistically significant, with reductions of 22% and 18%, respectively.

Notably, cardiovascular death reached nominal significance in the pooled analysis after narrowly missing it in an earlier pooled analysis limited to diabetic CKD trials (

= .076). Agarwal said this pattern, along with a parallel signal for all-cause mortality, represents a mortality benefit worth continued follow-up, since both cardiovascular and all-cause mortality comparisons were nominally significant across the pooled cohort.

Agarwal said the Infinity data support positioning finerenone as a foundational therapy to be layered in early alongside RAS and SGLT2 inhibitors, rather than reserved as a later-line option.

Finerenone selectively blocks the mineralocorticoid receptor, a pathway implicated in inflammation and fibrosis across multiple kidney disease etiologies, independent of glycemic status. 

The agent was first approved by the FDA in 2021 for adults with CKD associated with type 2 diabetes, based on the FIDELIO-DKD trial, which showed reduced risk of CKD progression and cardiovascular events compared with placebo in that population. 

FIND-CKD extends that evidence base to CKD without diabetes, a population that historically has had fewer disease-modifying options despite representing a substantial share of overall CKD cases.

What's Next: The SGLT2 Combination Question

Only about 17% of FIND-CKD participants were using an SGLT2 inhibitor at baseline, leaving the finerenone–SGLT2 inhibitor combination in nondiabetic CKD an open question. 

Of the roughly 14,500 participants in the Infinity pooled analysis, only about 1500 came from FIND-CKD itself, meaning the hard-outcome evidence in nondiabetic CKD still leans heavily on the diabetic trials within the pool. Agarwal pointed to a need for prospective combination data, including potassium and volume effects, adequately powered biopsy-confirmed studies in IgA nephropathy and FSGS, longer-term safety and durability data, and biomarker work to identify which patients benefit most.

Editor’s Note: Agarwal reports relevant disclosures with Alexion Pharmaceuticals, Inc. AstraZeneca, Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim, and others.

Heerspink HJL, Neuen BL, Agarwal R, et al. Finerenone in persons with chronic kidney disease without diabetes. N Engl J Med. Published online June 4, 2026. doi:10.1056/NEJMoa2604625

Neuen BL, Heerspink HJL, Perkovic V, et al. Efficacy and safety of finerenone in patients with chronic kidney disease: an individual participant data pooled analysis (INFINITY). Lancet. 2026;407(10546):2375-2386. doi:10.1016/S0140-6736(26)01009-3

Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229. doi:10.1056/NEJMoa2025845

Bayer. Phase III FIND-CKD results show Bayer's Kerendia (finerenone) improved eGFR slope and reduced risk of a composite kidney-cardiovascular outcome in adults with non-diabetic chronic kidney disease. Press release. June 5, 2026. 

https://www.bayer.com/en/us/news-stories/kerendia-for-non-diabetic-chronic-kidney-disease

Videos

Phase 3 FIND-CKD data show finerenone slows kidney decline and reduces CV events in adults with nondiabetic CKD, Rajiv Agarwal, MD, adds his perspective. 


FIND-CKD Expands Finerenone Evidence Beyond Diabetic CKD, With Rajiv Agarwal, MD

Finerenone (Kerendia) slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced kidney and cardiovascular events among adults with 

without diabetes, according to late-breaking phase 3 FIND-CKD data presented at the 63rd 

European Renal Association (ERA) Congress

The findings represent the first randomized placebo-controlled evidence evaluating finerenone in adults with CKD without diabetes, “It really removes the need to extrapolate from diabetic trials,” Rajiv Agarwal, MD, professor emeritus of medicine at Indiana University School of Medicine and staff physician at the Richard L. Roudebush VA Medical Center, told HCPLive.

In FIND-CKD, the mean annual rate of change in eGFR from baseline to month 32 was −3.3 mL/min/1.73 m² with finerenone compared with −4.0 mL/min/1.73 m² with placebo, corresponding to a 0.7 mL/min/1.73 m² slower decline with finerenone (95% Confidence Interval [CI], 0.3-1.1; 

Finerenone Proves CKD Benefit Extends Beyond Diabetes in FIND-CKD

Expanding the Role of Finerenone in CKD Care, With Brendon Neuen, MBBS, PhD

Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist that reduces mineralocorticoid receptor overactivation, a pathway associated with inflammation, fibrosis, and kidney injury.

Previous phase 3 trials demonstrated kidney and cardiovascular benefits with finerenone among adults with CKD associated with type 2 diabetes. FIND-CKD was designed to determine whether those benefits extended to adults with CKD without diabetes.

Although diabetes is a leading cause of CKD, a substantial proportion of patients with CKD do not have diabetes and historically have had fewer disease-modifying treatment options.

“Diabetic patients are not a niche group,” Agarwal said, noting that approximately 50% to 70% of CKD cases occur in adults without diabetes.

Beyond RAS blockade and SGLT2 inhibitors, these patients have had limited therapies with demonstrated kidney outcome benefits.

“The nonsteroidal MRA mechanism is not diabetes specific,” Agarwal said.

The phase 3 international, double-blind trial enrolled 1584 adults with CKD receiving maximally tolerated RAS blockade. Participants were randomized to finerenone (n = 793) or placebo (n = 791).

At baseline, mean eGFR was approximately 47 mL/min/1.73 m² in both groups.

After an initial increase in eGFR during the first 3 months, participants receiving finerenone experienced a slower chronic decline in kidney function.

At month 32, mean eGFR was 39.4 mL/min/1.73 m² with finerenone and 38.1 mL/min/1.73 m² with placebo.

Although the difference in annual eGFR slope was 0.7 mL/min/1.73 m², Agarwal emphasized that sustained changes in eGFR slope can be clinically meaningful because eGFR slope is a validated surrogate marker for kidney disease progression.

The composite kidney-cardiovascular outcome occurred in 13.9% of participants receiving finerenone compared with 16.9% receiving placebo (HR, 0.77; 95% CI, 0.60-0.99; P = .04).

Supporting Evidence Across CKD Populations

Agarwal noted that findings from FIND-CKD were further supported by an individual patient-level meta-analysis published in 

, which pooled data from FIND-CKD and previous phase 3 finerenone trials in adults with type 2 diabetes and CKD.

Across more than 14,500 participants, finerenone reduced the composite kidney outcome by 24% and the composite cardiovascular outcome by 20%, strengthening the evidence that mineralocorticoid receptor blockade provides benefits beyond diabetic CKD.

Safety findings were consistent with previous studies of finerenone.

Hyperkalemia occurred more frequently with finerenone, but few participants discontinued treatment or required hospitalization due to hyperkalemia. Rates of acute kidney injury were between groups.

FIND-CKD provides randomized evidence that finerenone may slow CKD progression among adults without diabetes, expanding the potential role of mineralocorticoid receptor antagonism across a broader CKD population.

FIND-CKD demonstrated reduced eGFR decline in patients with nondiabetic CKD, providing new data for a population of >50% of CKD cases. 

Who Benefits Most From CKD Combination Therapy? Breaking Down CONFIDENCE Trial Findings

The treatment paradigm for chronic kidney disease (CKD) is rapidly evolving, as clinicians move from a single-drug approach to a more complex, multi-therapy strategy. Over the past several years, the introduction of SGLT2 inhibitors, finerenone, and semaglutide alongside traditional RAAS blockade has created both new opportunities and new uncertainty around how best to deploy these therapies.

In an interview with HCPLive at World Congress of Nephrology (WCN) in Yokohama, Japan, Rajiv Agarwal, MD, MS, said this expanding toolkit has raised a critical question as to whether therapies should be introduced sequentially or started together. While clinicians have historically taken a stepwise approach titrating one agent at a time, he notes that this process can take up to a year, time during which ongoing kidney and cardiovascular damage may continue.

In response, the CONFIDENCE trial was designed to evaluate whether simultaneous initiation of combination therapy could accelerate benefit without compromising safety. He explains that this was the first adequately powered study to assess starting therapies such as finerenone and SGLT2 inhibitors at the same time. While prior studies evaluated add-on strategies, they did not address the safety and efficacy of concurrent initiation.

Concerns going into the trial included the potential for hypotension, acute kidney injury, and hyperkalemia, particularly given the hemodynamic effects of these agents. The findings, however, demonstrated that combination therapy could achieve meaningful reductions in albuminuria both safely and effectively.

A pair of additional analyses from CONFIDENCE presented at WCN offer further insight into patient response. The first examined differences by sex and age, revealing that women experienced approximately 20% greater reductions in urinary albumin-to-creatinine ratio compared with men. Agarwal noted that older patients also demonstrated enhanced responses, with each decade of age associated with a roughly 10% greater likelihood of benefit. Of note, these gains were not accompanied by increased safety concerns, challenging assumptions about treating higher-risk populations.

The second analysis addressed early declines in estimated glomerular filtration rate (eGFR), a common concern when initiating these therapies. Agarwal emphasizes that these initial dips are typically reversible and not predictive of long-term harm. Rather than discontinuing treatment, clinicians should monitor patients closely, particularly if eGFR declines exceed 30%, and adjust contributing factors such as volume status or concomitant medications.

Ultimately, he underscores that multimodal therapy represents the future of CKD management. Early and sustained use of combination treatment, he suggests, has the potential to significantly reduce cardiovascular events and extend patient survival.

Editors’ note: Relevant disclosures for Agarwal include Akebia Therapeutics, Alnylam, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Intercept, Novartis, and others.

Campbell P. CONFIDENCE: SGLT2i and Finerenone Effective, Safe to Initiate Simultaneously in CKD. HCPLive. June 5, 2025. Accessed April 2, 2026. 

https://www.hcplive.com/view/confidence-sglt2i-and-finerenone-effective-safe-to-initiate-simultaneously-in-ckd

Agarwal R. Effect of Simultaneous Initiation of Finerenone and Empagliflozin on Urinary Albumin-to-creatinine Ratio by Age and Sex in the CONFIDENCE Trial. Presented at World Congress of Nephrology (WCN) in Yokohama, Japan, March 28-31, 2026.

Agarwal R. Estimated Glomerular Filtration Rate, Systolic Blood Pressure, and Urinary Albumin-to-creatinine Ratio — Unravelling the Interplay in Combination: Findings From the CONFIDENCE Trial. Presented at World Congress of Nephrology (WCN) in Yokohama, Japan, March 28-31, 2026.

Further CONFIDENCE analyses support safe combination therapy in CKD, with improved responses in key patient subgroups.

CONFIDENCE Trial Insights on CKD Combination Therapy, With Rajiv Agarwal, MD, MS

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

HCPLive Five at European Renal Association (ERA) Congress 2025

 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 

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.

Rajiv Agarwal, MD, MS

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