Article
Pharmacology & Pharmacy
Peter Kolkhof, Amer Joseph, Ulrich Kintscher
Summary: Over the past 30 years, there has been significant progress in understanding the role of aldosterone and mineralocorticoid receptor in cardiovascular and kidney diseases. Ongoing research is focused on developing safer and more effective nonsteroidal MR antagonists.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Kennosuke Ohashi, Takeshi Hayashi, Kazunori Utsunomiya, Rimei Nishimura
Summary: High glucose conditions induce Muller cell swelling through activation of MR signaling, resulting in increased MR protein and mRNA levels. MR transcriptional activity is enhanced and related genes are upregulated. MR antagonists can suppress these effects.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Peripheral Vascular Disease
George Bakris, Pablo E. Pergola, Belkis Delgado, Diyan Genov, Tamar Doliashvili, Nam Vo, Y. Fred Yang, James McCabe, Vincent Benn, Bertram Pitt
Summary: In patients with resistant or poorly controlled hypertension and advanced chronic kidney disease, the nonsteroidal mineralocorticoid receptor antagonist KBP-5074 effectively lowers blood pressure with some risk of hyperkalemia.
Review
Pharmacology & Pharmacy
Daiji Kawanami, Yuichi Takashi, Yoshimi Muta, Naoki Oda, Dai Nagata, Hiroyuki Takahashi, Makito Tanabe
Summary: Diabetic kidney disease is a major cause of end-stage kidney disease worldwide, with the mineralocorticoid receptor playing an important role in its development. Clinical studies have shown the benefits of MR antagonists for DKD, but concerns remain about their selectivity and hyperkalemia risks. New nonsteroidal MRAs, such as finerenone, have been developed with high selectivity and potent anti-inflammatory and anti-fibrotic properties, and a lower risk of hyperkalemia.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Ophthalmology
Jianan Duan, Yun Zhang, Meixia Zhang
Summary: The mineralocorticoid receptor antagonist (MRA) treatment can improve anatomical structure in central serous chorioretinopathy (CSC) patients, but it is not effective for achieving best-corrected visual acuity (BCVA) gain. The application of MRA is safe and does not have severe side effects.
Review
Medicine, General & Internal
Gates B. Colbert, Mohamed E. Elrggal, Anna Gaddy, Hector M. Madariaga, Edgar V. Lerma
Summary: Hypertension is a key factor in the progression of cardiovascular disease in patients with chronic kidney disease, particularly diabetic kidney disease. Controlling hypertension can delay the progression of diabetic kidney disease. Several medications have been proven effective in real-world use, and new drugs are emerging.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Endocrinology & Metabolism
Nikshay Karthigan, Siobhan Lockwood, Anthony White, Jun Yang, Morag J. Young
Summary: The mineralocorticoid receptor plays an important role in heart failure, but its treatment benefit is unclear for patients with preserved ejection fraction. Currently, there are no biomarkers available to predict treatment response, but finding such biomarkers is crucial for improving treatment efficacy and avoiding unnecessary side effects.
JOURNAL OF ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Xurong Mai, Mitsuhiro Kometani, Takashi Yoneda
Summary: This review summarizes previous studies on autonomous aldosterone production. It discusses the inhibitory effects of mineralocorticoid receptor antagonists (MRAs) on steroid synthesis and considers the possible factors of cytochrome P-450 reduction. Clinical research reveals the association between aldosterone-producing adenoma and cells containing spironolactone bodies. Furthermore, long-term treatment with MRAs has been reported to lead to spontaneous remission of primary aldosteronism in some cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Vishal Patel, Amit Joharapurkar, Mukul Jain
Summary: Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, have shown therapeutic effects in treating hypertension and chronic kidney disease. New generation nonsteroidal MRAs like esaxerenone have lower risk of hyperkalemia and may provide optimal therapeutic benefits for patients with kidney diseases.
DRUG DEVELOPMENT RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ixchel Lima-Posada, Yohan Stephan, Matthieu Soulie, Roberto Palacios-Ramirez, Benjamin Bonnard, Lionel Nicol, Peter Kolkhof, Frederic Jaisser, Paul Mulder
Summary: The mineralocorticoid receptor (MR) plays a crucial role in CKD and cardiovascular complications. Finerenone, a non-steroidal MR antagonist, has shown benefits in improving cardiac function in a preclinical HFpEF model. It ameliorates diastolic dysfunction and improves cardiac perfusion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Zhejia Tian, Clara Vollmer Barbosa, Hannah Lang, Johann Bauersachs, Anette Melk, Bernhard M. W. Schmidt
Summary: This study compared the effectiveness of pharmacologic and interventional treatments for resistant hypertension through a network meta-analysis. The results showed that spironolactone is the most effective pharmacologic treatment in reducing blood pressure in patients with resistant hypertension, while lifestyle modification is the most effective non-pharmacologic treatment.
CARDIOVASCULAR RESEARCH
(2023)
Review
Endocrinology & Metabolism
Morag J. Young, Monica Kanki, Nikshay Karthigan, Penny Konstandopoulos
Summary: Mineralocorticoid receptor antagonists, also known as aldosterone blockers, have been widely recognized for their clinical benefits in treating heart failure, improving outcomes for both HFrEF and HFpEF patients. As research continues to evolve, new nonsteroidal receptor antagonists like esaxerenone and finerenone have emerged, showcasing the constantly evolving landscape of cardiovascular disease treatment.
Review
Endocrinology & Metabolism
Morag J. Young, Monica Kanki, Nikshay Karthigan, Penny Konstandopoulos
Summary: Mineralocorticoid receptor (MR) antagonists, also known as aldosterone blockers, have shown clinical benefits in treating patients with heart failure, including those with reduced ejection fraction and preserved ejection fraction with reduced left ventricular filling. The MR has various physiological and pathophysiological roles in the heart, vasculature, and other tissues, which underpin the use of MR antagonists in cardiovascular disease, particularly heart failure. The development of MR antagonists has progressed from potassium-sparing diuretics to more receptor-selective options, demonstrating the evolution of treatment options for cardiovascular diseases.
Article
Transplantation
Rajiv Agarwal, Stefan D. Anker, George Bakris, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Luis Ruilope, Martin Gebel, Peter Kolkhof, Christina Nowack, Amer Joseph
Summary: Research has found that finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, can protect the kidneys and hearts of patients with chronic kidney disease and type 2 diabetes. The FIDELIO-DKD and FIGARO-DKD trials are investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes in T2D patients with different stages of kidney disease.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Peripheral Vascular Disease
Ryo Nakamaru, Koichi Yamamoto, Hiroshi Akasaka, Hiromi Rakugi, Isao Kurihara, Takashi Yoneda, Takamasa Ichijo, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Tetsuya Yamada, Hiroki Kobayashi, Kouichi Tamura, Yoshihiro Ogawa, Junji Kawashima, Nobuya Inagaki, Megumi Fujita, Kenji Oki, Kohei Kamemura, Akiyo Tanabe, Mitsuhide Naruse
Summary: The study found that female patients with bilateral primary aldosteronism have worse renal outcomes compared to male patients after receiving mineralocorticoid receptor antagonist treatment. Despite similar systolic blood pressure levels between the sexes, women experienced a greater decline in estimated glomerular filtration rate, especially during the late phase of 6 to 60 months post-treatment initiation.
