"Kerendia for integrated management of kidney and heart health"

Treatment strategy is shifting

Has expanded clinical areas, including heart failure·non-diabetic CKD

The importance of early intervention utilizing a combination strategy according to individual patient risk profiles is rising

"Chronic kidney disease associated with diabetes must be treated from the moment proteinuria is confirmed. Intervening early while kidney function is still sufficiently intact can make a difference in a patient's long-term lifetime prognosis."

Professor Brendon Neuen, a nephrologist at Royal North Shore Hospital in Australia, shared this clinical insight during a recent meeting with DailyPharm, emphasizing that the management of chronic kidney disease (CKD) is rapidly shifting toward an integrated approach that simultaneously protects both the heart and the kidneys.

Professor Brendon Neuen, a nephrologist at Royal North Shore Hospital in Australia

According to Professor Neuen, the emergence of novel therapeutic options, such as 'Kerendia (finerenone),' has expanded therapeutic goals beyond merely slowing the decline of renal function to managing cardiovascular risk. From now, he anticipates that personalized, risk-based strategies that modulate treatment intensity according to individual patient risk profiles will establish themselves as the new standard of care.

The therapeutic landscape for CKD has evolved over recent years. Previously, management relied on renin-angiotensin system (RAS) inhibitors to regulate systemic blood pressure and manage proteinuria. The subsequent introduction of SGLT2 inhibitors introduced a new paradigm, establishing concurrent renal protection and cardiovascular risk reduction as primary clinical endpoints.

The emergence of Kerendia, a non-steroidal mineralocorticoid receptor antagonist (MRA), has enabled clinicians to directly target and modulate both inflammation and fibrosis. Overactivation of the mineralocorticoid receptor is known to drive pathological changes across the heart, vasculature, and kidneys. Kerendia is particularly effective in disrupting this cascade by actively suppressing inflammation and fibrotic progression.

The paradigm shift is driven by high disease burden associated with diabetic kidney disease. Diabetes remains the leading etiology of CKD worldwide, and its clinical complications extend far beyond progressive renal decline. 

Patients who have concurrent diabetes and CKD face elevated risks of cardiovascular events, such as heart failure and myocardial infarction, alongside the risk of end-stage renal disease (ESRD). Notably, a significant proportion of this patient cohort succumbs to cardiovascular mortality before ever progressing to maintenance dialysis.

Consequently, the Cardiovascular-Kidney-Metabolic (CKM) framework has emerged as a dominant therapeutic paradigm, treating renal decline and cardiovascular risk as interconnected pathologies.

Because diabetes, CKD, and heart failure affect once another, accelerating disease progression and elevating mortality risk, clinical consensus strongly favors integrated, multi-organ management over isolated, organ-specific interventions. Reflecting this trend, major international clinical practice guidelines have shifted toward holistic cardio-renal protection and risk-stratified therapeutic intensification.

Meanwhile, Kerendia is expanding its clinical areas. Based on the FIDELIO-DKD and FIGARO-DKD trials, which demonstrated significant reductions in renal decline and major adverse cardiovascular events (MACE) in patients with CKD and type 2 diabetes, the FIDELITY analysis further confirmed the drug's consistent therapeutic efficacy. 

More recently, Kerendia has expanded its clinical application into broader fields, including heart failure, non-diabetic CKD, and combination therapy paradigms, through ongoing and subsequent trials such as FINEARTS-HF, FIND-CKD, and CONFIDENCE.

As a leading investigator in the CKM field, Professor Neuen has served as a co-author on the core FIDELIO-DKD, FIGARO-DKD, and FIDELITY trials and currently serves on the Steering Committee for the FIND-CKD trial.

He is recognized as an expert leading the CKM paradigm  shift through his extensive research into integrated cardio-renal management and risk-based treatment strategies.

Professor Neuen said, "Recently presented clinical data have significantly broadened both the target patient populations and the strategic boundaries of CKD management," and added "The future standard of care will center on risk-stratified, personalized medicine that manages both the heart and kidneys.

Q. What is the optimal stage for initiating early therapeutic intervention in patients with diabetic kidney disease?

The ideal window for early detection and intervention occurs when the estimated glomerular filtration rate (eGFR) is maintained above 90, or at the very least above 60, signifying relatively well-preserved baseline renal function. The critical objective is to identify and treat patients at this early, preserved stage when kidney function remains intact but the initial signal of structural damage, such as proteinuria, is detected.

A vast number of patients globally, including in South Korea, remain unaware that they present with persistent proteinuria despite showing normal standard serum creatinine or eGFR metrics. An elevation in proteinuria represents the definitive primary biomarker of progressive renal injury. 

If a patient is diagnosed only at an advanced stage, when renal function is largely depleted, and eGFR drops below 30, the residual functional nephron mass is severely diminished, meaning that even optimal therapeutic interventions will have significantly limited clinical utility.

Q. Could you elaborate on the clinical necessity of integrated management across cardiovascular, renal, and metabolic diseases?

The physiological interconnectedness of cardiovascular, renal, and metabolic pathologies is not a new concept. The co-occurrence of cardiac abnormalities in patients with established renal disease was first documented over two centuries ago. However, this axis has recently entered mainstream clinical discourse due to two major developments. 

First, our understanding of shared pathophysiological pathways and reciprocal mechanisms has deepened significantly, and second, we now possess therapeutic agents capable of modifying multiple disease pathways simultaneously. For example, GLP-1 receptor agonists and SGLT2 inhibitors. Most recently, Kerendia has demonstrated the capacity to simultaneously mitigate the risk of heart failure hospitalizations and renal progression, while additionally lowering the incidence of new-onset type 2 diabetes. 

The emergence of these multi-disease therapeutics allows clinicians to diagnose and treat patients from a more systemic perspective. This requires specialists across nephrology, cardiology, and endocrinology to break down clinical siloes, evaluate patient risk profiles through a broader lens, and deploy integrated treatment regimens.

Crucially, these organ systems affect one another. An exacerbation of heart failure accelerates the progression of underlying kidney disease, while a deterioration in renal function conversely destabilizes cardiac output and worsens heart failure. Ultimately, these conditions form a pathological feedback loop, driving mutual deterioration through shared metabolic and hemodynamic risk factors.

Q. What are your primary criteria for patient selection, and how do you evaluate therapeutic response?

In terms of patient selection, my primary focus centers on whether a patient exhibits persistent residual albuminuria or proteinuria despite receiving optimized, maximum-tolerated background therapy with a standard RAS inhibitor and an SGLT2 inhibitor. Persistent protein excretion serves as an objective sign that progressive renal injury is actively continuing despite standard intervention. Therefore, if a patient continues to demonstrate elevated urine albumin-to-creatinine ratios under an optimized baseline regimen, I proactively initiate combination therapy by adding Kerendia.

The reason for prioritizing combination therapy is that complex, multifaceted, and redundant biological pathways drive CKD progression. Effectively disrupting this disease process and securing optimal patient outcomes requires the simultaneous blockade of these distinct pathogenic streams.

In fact, data from the FIND-CKD trial demonstrate that this combination approach can be the standard of care even in non-diabetic CKD populations, where historical therapeutic options have been highly constrained. Synthesizing recent FIND-CKD data with data from the CONFIDENCE trial, which evaluates the upfront combination of Kerendia and an SGLT2 inhibitor in patients with CKD and type 2 diabetes, makes it clear that combination regimens will assume a pivotal role in concurrently managing both renal attrition and systemic cardiovascular risk.

Q.  As a researcher for the FIND-CKD trial, could you explain the core findings of the study?

The FIND-CKD trial was a randomized clinical study that enrolled 1,584 patients with non-diabetic chronic kidney disease to evaluate the efficacy of Kerendia in suppressing renal progression. While Kerendia's ability to delay renal decline and reduce cardiovascular events in patients with type 2 diabetes was already firmly established, whether these precise clinical benefits would translate to a non-diabetic CKD cohort had remained unverified.

The trial data revealed that patients randomized to the Kerendia group experienced a significant deceleration in the chronic eGFR slope, with the annual rate of decline slowing from 4.0 mL/min per year in the control arm to 3.3 mL/min per year. While an absolute difference of 0.7 mL/min per year might appear modest on the surface, it culminated in a substantial 23% risk reduction in the primary composite endpoint, which aggregated the incidence of kidney failure, a sustained eGFR decline of 57% or greater, hospitalization for heart failure, and cardiovascular mortality.

Notably, this therapeutic benefit remained remarkably consistent regardless of the underlying etiology of kidney disease, baseline renal function metrics, or concurrent baseline use of SGLT2 inhibitors. From a safety perspective, although the incidence of laboratory-monitored hyperkalemia was higher in the Kerendia cohort compared to the placebo group, clinically significant hyperkalemia events resulting in permanent treatment discontinuation or acute hospitalization were exceptionally rare.

It is significant that approximately half of the total cohort across the 24 participating nations consisted of Asian patients, with South Korean patients accounting for roughly 10% of the overall study population. This substantial regional representation provides highly actionable, high-value evidence directly generalizable to real-world clinical practice across Asia and South Korea.

Q. How do you evaluate the overall clinical value proposition of these findings?

It is significant that Kerendia's established efficacy in diabetic kidney disease extends consistently into the non-diabetic CKD patients.

It demonstrates that Kerendia can effectively address a broad patient demographic characterized by a severe, historical lack of treatment options. Anchored by the findings of FIND-CKD alongside the broader clinical trial portfolio, the molecule has demonstrated its potential to solidify its position as an essential, foundational therapeutic axis for both diabetic and non-diabetic CKD management.

Kerendia's renal-protective benefit was consistently demonstrated across diverse clinical etiologies and baseline sub-segments, and the safety profile confirmed excellent overall tolerability that aligned with investigator expectations. When these findings were officially unveiled at the international congress, the atmosphere among the attending delegates reflected a shared consensus that we were witnessing a milestone advancement in renal medicine. It was the moment the medical community collectively recognized that Kerendia could serve as a core cornerstone of long-term kidney disease management.

Q. What direction should chronic kidney disease management take?

Personally, I believe the management of kidney disease is systematically transitioning toward a strict "risk-based approach." Under this paradigm, when a patient presents with heavily elevated baseline proteinuria and is stratified into a high-risk category, clinicians must initiate intensive combination therapy as early as possible within the treatment algorithm.

Data from the CONFIDENCE trial provide strong evidence for an upfront, simultaneous initiation strategy using both an SGLT2 inhibitor and Kerendia on top of a foundational RAS inhibitor. For patients identified as high risk, our clinical mandate should be to deploy the full complement of validated, disease-modifying therapeutics with the utmost clinical urgency.

Q. How are real-world prescribing trends shifting, and how do you project the future of the CKM integrated framework?

There has been a rapid escalation in the clinical adoption and real-world uptake of GLP-1 receptor agonists, SGLT2 inhibitors, and Kerendia. For example, in recent clinical trial settings, the baseline utilization rate of SGLT2 inhibitors has climbed to 50%-60%. Compared with the 10% to 15% adoption rate observed when we initiated the FIND-CKD trial in 2020, clinical penetration within controlled study environments has progressed at an impressive pace.

There has been a rapid escalation in the clinical adoption and real-world uptake of GLP-1 receptor agonists, SGLT2 inhibitors, and Kerendia. For example, in recent clinical trial settings, the baseline utilization rate of SGLT2 inhibitors has climbed to 50%-60%. Compared with the 10% to 15% adoption rate observed when we initiated the FIND-CKD trial in 2020, clinical penetration within controlled study environments has progressed at an impressive pace.