Patients with chronic kidney disease (CKD) are at high risk of developing cardiovascular complications. While sodium-glucose cotransporter-2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) have shown individual benefits in treating CKD, their combined effects remained unclear. In a new study, researchers found that the combination of the SGLT2 inhibitor dapagliflozin and the MRA eplerenone can significantly improve diastolic function, reduce cardiac fibrosis, and enhance myocardial perfusion in a non-diabetic CKD rat model. These findings suggest that the combination therapy may be a promising approach for managing cardiovascular complications in CKD patients, even those without diabetes. The study highlights the complex interplay between the kidney and the heart, and the potential for targeted therapies to address this cardiorenal syndrome.
Chronic Kidney Disease and Cardiovascular Complications
Chronic kidney disease (CKD) and cardiovascular disease are closely linked, with the deterioration of one often leading to the deterioration of the other. Patients with CKD are at a high risk of developing cardiovascular complications, such as mellitus’>diabetes. In recent years, the introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) has shown promise in improving cardiovascular and renal outcomes in CKD patients, both with and without diabetes.
The Benefits of Combination Therapy
In this new study, researchers aimed to investigate the effects of combining an SGLT2 inhibitor (dapagliflozin) and an MRA (eplerenone) in a non-diabetic rat model of CKD. The researchers induced CKD in rats through a surgical procedure and then treated them with dapagliflozin, eplerenone, or a combination of the two for three months.
The key findings of the study include:
Improved Diastolic Function: The combination therapy significantly improved measures of diastolic function, such as left ventricular end-diastolic pressure and the left ventricular end-diastolic pressure-volume relationship, compared to either treatment alone or the untreated CKD group.
Reduced Cardiac Fibrosis: Both dapagliflozin and eplerenone alone were able to reduce cardiac fibrosis in the CKD rats, but the combination therapy had an even greater effect, suggesting an additive benefit.
Enhanced Myocardial Perfusion: While dapagliflozin alone did not affect myocardial perfusion, eplerenone treatment or the combination therapy improved cardiac perfusion compared to the untreated CKD group.
These findings suggest that the combination of an SGLT2 inhibitor and an MRA may be a promising approach for managing the cardiovascular complications associated with CKD, even in the absence of diabetes.
Potential Mechanisms and Clinical Implications
The researchers believe that the combination therapy may have beneficial effects on failurewithpreservedejectionfraction’>heart failure with preserved ejection fraction, two common issues in CKD patients.
The improved diastolic function and reduced cardiac fibrosis observed with the combination therapy may be related to the drugs’ ability to reduce inflammation, oxidative stress, and the activation of the renin-angiotensin-aldosterone system, all of which contribute to the development of cardiovascular complications in CKD.
While further clinical research is needed, these findings suggest that the combination of an SGLT2 inhibitor and an MRA could be a valuable treatment strategy for CKD patients, regardless of their diabetes status. By targeting multiple pathways involved in the cardiorenal syndrome, this approach may help slow the progression of both kidney and heart disease in this high-risk population.
Author credit: This article is based on research by M. Soulié, Y. Stephan, M. Durand, I. Lima-Posada, R. Palacios-Ramírez, L. Nicol, N. Lopez-Andres, P. Mulder, F. Jaisser.
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