Mineralocorticoid receptor antagonism for non-diabetic kidney disease DOI Creative Commons
Frédéric Jaisser, Jonatan Barrera‐Chimal

Nephrology Dialysis Transplantation, Journal Year: 2024, Volume and Issue: 40(Supplement_1), P. i29 - i36

Published: Nov. 11, 2024

The use of mineralocorticoid receptor antagonists (MRAs) in preclinical models non-diabetic chronic kidney disease (CKD) has consistently shown a beneficial effect by preventing renal structural injury, reducing albuminuria and preserving function. In this context, MR activation non-epithelial cells contributes to injury through the inflammatory fibrotic pathways, increasing oxidative stress modulating hemodynamics. protective effects MRAs animal CKD are not restricted kidney. Cardiovascular benefits, such as prevention cardiac fibrosis, hypoperfusion vascular calcification, have also been observed. translation these findings into clinical practice difficult, mainly due lack studies testing efficacy steroidal patients their contraindication because an increased risk hyperkalemia patients. Here, we review latest evidence showing new mechanisms which inhibition results against cardiorenal damage disease. Moreover, summarize trials safety non-steroidal with advanced CKD. (MR) is known for its role regulation sodium potassium balance distal tubules However, under pathological conditions other cell types (including vasculature immune cells) leads harmful effects, damaging main components kidney, ultimately causing dysfunction. Over past 20 years, several performed mouse rat that using specific drug class inhibits (MR antagonists: MRAs) positively impacts preservation structure helps prevent decline function, thus positioning good therapeutic option diseases from origin. addition, benefited cardiovascular system health improved functional parameters well calcification blood vessels. Nevertheless, important barrier translating could lead serum levels, particularly patients, adverse life-threatening arrhythmias. review, data evidences benefits evaluated including those tested generation (non-steroidal expected reduce frequency while retaining benefits.

Language: Английский

Mineralocorticoid Antagonism in Heart Failure: Established and Emerging Therapeutic Role DOI

Joycie Chang,

Andrew P. Ambrosy, Orly Vardeny

et al.

JACC Heart Failure, Journal Year: 2024, Volume and Issue: 12(12), P. 1979 - 1993

Published: Sept. 1, 2024

Language: Английский

Citations

6
Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease DOI Creative Commons
Matthieu Soulié, Yannick Stéphan, Manon Durand

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 14, 2024

Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects non-diabetic CKD remain unclear. This study aimed evaluated whether the combination Dapagliflozin (DAPA) and Eplerenone (EPLE) would positive on cardiorenal functions model. was induced rats via 5/6 nephrectomy, followed by treatment DAPA (5 mg/kg/day PO), EPLE (100 PO) or for 3 months following induction. Cardiorenal were assessed after period. All treated groups showed reduced fibrosis plasma creatinine urea levels remained unchanged. Compared untreated DAPA/EPLE left ventricle (LV) end-diastolic pressure LV volume relationship, whereas alone did not achieve significant reductions. improved cardiac perfusion but not. Cardiac blunted either alone, showing an additive effect. conclusion, co-treatment enhances diastolic function, reduces myocardial rats.

Language: Английский

Citations

1
Mineralocorticoid Receptor and Sleep Quality in Chronic Kidney Disease DOI Open Access

Juan de la Puente-Aldea,

Oscar Lopez-Llanos,

Daniel Horrillo

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12320 - 12320

Published: Nov. 16, 2024

The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume blood pressure. MR expressed in central nervous system (CNS) involved regulation hypothalamic–pituitary–adrenal (HPA) axis as well sleep physiology, playing a role non-rapid eye movement (NREM) phase sleep. Some patients with psychiatric disorders have very poor quality, relationship between dysregulation this disorder has been found them. In addition, renal peripheral clock. One most common comorbidities observed chronic kidney disease (CKD) quality. Patients CKD experience disturbances, including reduced duration, fragmentation, insomnia. To date, no studies specifically investigated activation CKD-associated disturbances. However, review, we analyzed environment that occurs proposed two MR-related mechanisms may be responsible for these disturbances: circadian clock disruption high levels agonist CKD.

Language: Английский

Citations

0
Mineralocorticoid receptor antagonism for non-diabetic kidney disease DOI Creative Commons
Frédéric Jaisser, Jonatan Barrera‐Chimal

Nephrology Dialysis Transplantation, Journal Year: 2024, Volume and Issue: 40(Supplement_1), P. i29 - i36

Published: Nov. 11, 2024

The use of mineralocorticoid receptor antagonists (MRAs) in preclinical models non-diabetic chronic kidney disease (CKD) has consistently shown a beneficial effect by preventing renal structural injury, reducing albuminuria and preserving function. In this context, MR activation non-epithelial cells contributes to injury through the inflammatory fibrotic pathways, increasing oxidative stress modulating hemodynamics. protective effects MRAs animal CKD are not restricted kidney. Cardiovascular benefits, such as prevention cardiac fibrosis, hypoperfusion vascular calcification, have also been observed. translation these findings into clinical practice difficult, mainly due lack studies testing efficacy steroidal patients their contraindication because an increased risk hyperkalemia patients. Here, we review latest evidence showing new mechanisms which inhibition results against cardiorenal damage disease. Moreover, summarize trials safety non-steroidal with advanced CKD. (MR) is known for its role regulation sodium potassium balance distal tubules However, under pathological conditions other cell types (including vasculature immune cells) leads harmful effects, damaging main components kidney, ultimately causing dysfunction. Over past 20 years, several performed mouse rat that using specific drug class inhibits (MR antagonists: MRAs) positively impacts preservation structure helps prevent decline function, thus positioning good therapeutic option diseases from origin. addition, benefited cardiovascular system health improved functional parameters well calcification blood vessels. Nevertheless, important barrier translating could lead serum levels, particularly patients, adverse life-threatening arrhythmias. review, data evidences benefits evaluated including those tested generation (non-steroidal expected reduce frequency while retaining benefits.

Language: Английский

Citations

0