Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease

Abstract

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Keywords: angiotensin receptor blocker; chronic kidney disease; heart failure preserved ejection fraction; hyperkalemia; neprilysin inhibitors; sodium–glucose-linked transporters 2 inhibitors; treatment.

Figure 1

Management of HF drugs in HFpEF and different phenotypes. HFpEF (heart failure with preserved ejection fraction), CKD (chronic kidney disease), SGLT2-i (sodium–glucose transport protein 2 inhibitors), eGFR (estimated glomerular filtration rate), NDH-Ca²⁺ antagonists (non-dihydropyridine calcium channel antagonists), ACEi (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor blockers), CCB (calcium channel blockers), T-diuretics (thiazide diuretics), TL-diuretics (thiazide-like diuretic), BP (blood pressure), MRA (mineral receptor antagonist), GLP-1a (glucagon-like peptide 1 agonists).