Nephrological perspectives on the underutilization of SGLT2is in heart failure and chronic kidney disease

Abstract

We read with great interest the study by Kocabaş and colleagues, which brings attention to the suboptimal use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in heart failure (HF), particularly in patients with chronic kidney disease (CKD), where these drugs should be regarded as cornerstone therapies.¹

The RED-HEART study involving 1923 patients highlights that SGLT2is are disproportionately prescribed to patients with more severe disease. This feature is evidenced by the higher proportion of New York Heart Association Class IV cases and the increased concomitant use of angiotensin receptor-neprilysin inhibitors (ARNis), mineralocorticoid receptor antagonists (MRAs), and diuretics. This prescribing pattern underscores a concerning trend: SGLT2is are often perceived as add-on therapies for advanced cases rather than essential treatments in HF management. As the authors note, clinical inertia likely contributes to this suboptimal integration of SGLT2is into standard care, limiting their potential to significantly improve outcomes.¹

HF and CKD are intricately intertwined, as the two conditions frequently coexist and share overlapping risk factors, pathophysiological mechanisms, and therapeutic targets. This interconnectedness underscores the importance of therapies like SGLT2is, which provide both cardiovascular and renal benefits.² The findings of the RED-HEART study present an opportunity to explore these renal aspects in greater depth.

The study does not clarify key methodological details, such as which estimated glomerular filtration rate (eGFR) formula was used (e.g., Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease) or the specific cut-off values applied to define CKD. These details are crucial for interpreting the characteristics and outcomes of the CKD subgroup within this cohort.

Although GFR staging and albuminuria are central to CKD assessment, neither appears to have been explicitly reported.³ Albuminuria, in particular, is a marker not only of CKD severity but also of significant prognostic value in HF.⁴ Including these metrics would provide a more nuanced understanding of the interplay between HF and CKD in the study population.

The cohort's median eGFR around 70 mL/min suggests that patients with stage 3B and 4 (combined eGFR between 15 and 45 mL/min) were likely excluded. Furthermore, the CKD prevalence of 28% in the cohort is notably lower than the 40%–50% typically reported in HF trials.⁵ This discrepancy likely reflects differences between real-world data and clinical trial populations.

It is well-established that as CKD progresses, HF with preserved ejection fraction (HFpEF) becomes more prevalent compared to HF with reduced ejection fraction (HFrEF).⁶ In practice, distinguishing whether fluid overload in patients with both HFpEF and CKD is primarily driven by cardiac dysfunction or renal impairment is often challenging, if not impossible. Despite these complexities, the markedly low usage rate of SGLT2is in the CKD group (38%) is a cause for concern and warrants urgent attention.

Barriers to the use of SGLT2 inhibitors are not limited to cardiology; similar challenges are encountered in nephrology. Despite clear Kidney Disease: Improving Global Outcomes (KDIGO) recommendations, recent data from the United Kingdom show that less than 30% of patients meeting eligibility criteria receive SGLT2is.⁷ This continued underutilization reflects widespread concerns, with fear of acute kidney injury (AKI) remaining a major barrier.

We fully agree with the authors' assertion that concerns regarding AKI associated with SGLT2is are unfounded. On the contrary, accumulating evidence suggests that SGLT2is even may reduce the risk of AKI.⁸ Similar to ACE inhibitors, ARNI, MRAs, metformin, and other medications, SGLT2is are also subject to the sick day rule, which highlights the need to temporarily discontinue these medications during periods of acute illness or dehydration to prevent further renal harm.⁹

Both the DAPA-CKD (dapagliflozin) and EMPA-KIDNEY (empagliflozin) trials have unequivocally established the safety and efficacy of these agents in patients with eGFRs as low as 25 and 20 mL/min, respectively.² Furthermore, continuation studies have demonstrated that SGLT2is can be safely used until patients transition to dialysis, a recommendation supported by KDIGO guidelines, which advocate for their continuation until the dialysis phase.³ Preliminary data from haemodialysis (HD) and peritoneal dialysis (PD) populations have similarly shown no additional safety concerns.¹⁰ However, SGLT2is should not be used in HD and PD patients—outside clinical trials—for the time being due to insufficient efficacy data.³

In this regard, we eagerly await the results of ongoing trials such as The RENAL LIFECYCLE Trial: A RCT to Assess the Effect of Dapagliflozin on Renal and Cardiovascular Outcomes in Patients With Severe CKD (NCT05374291), which aims to evaluate the effects of dapagliflozin on major adverse cardiovascular events in patients on HD, PD, and renal transplant recipients. These findings could expand the use of SGLT2 inhibitors in cardiorenal spectrum.

We propose structured educational initiatives and greater collaboration between cardiologists and nephrologists to address gaps in SGLT2i prescription practices. These could include workshops on updated guidelines and strategies to overcome misconceptions and clinical inertia, particularly in CKD populations.

Our gratitude goes to the authors for their substantial contribution to this critical field. If additional nephrological data are available, we would be pleased to read and appreciate it.