Synergistic reduction in albuminuria in type 2 diabetic mice by esaxerenone (CS-3150), a novel nonsteroidal selective mineralocorticoid receptor blocker, combined with an angiotensin II receptor blocker.
Albuminuria
/ drug therapy
Angiotensin II Type 1 Receptor Blockers
/ pharmacology
Animals
Blood Pressure
/ drug effects
Diabetes Mellitus, Type 2
/ complications
Diabetic Nephropathies
/ drug therapy
Drug Evaluation, Preclinical
Drug Therapy, Combination
Imidazoles
/ pharmacology
Male
Mice, Inbred C57BL
Mineralocorticoid Receptor Antagonists
/ pharmacology
Pyrroles
/ pharmacology
Sulfones
/ pharmacology
Tetrazoles
/ pharmacology
Albuminuria
Angiotensin II receptor blocker
Diabetic nephropathy
Esaxerenone
Mineralocorticoid receptor blocker
Journal
Hypertension research : official journal of the Japanese Society of Hypertension
ISSN: 1348-4214
Titre abrégé: Hypertens Res
Pays: England
ID NLM: 9307690
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
09
01
2020
accepted:
22
05
2020
revised:
19
05
2020
pubmed:
4
7
2020
medline:
12
10
2021
entrez:
4
7
2020
Statut:
ppublish
Résumé
Esaxerenone is a novel selective mineralocorticoid receptor (MR) blocker that was recently approved in Japan to treat hypertension. In phase II and III studies, esaxerenone plus a renin-angiotensin system inhibitor markedly reduced the urinary albumin-to-creatinine ratio (UACR) in hypertensive patients with diabetic nephropathy. To evaluate a direct renoprotective effect by MR blockade independent of an antihypertensive effect in the context of diabetic nephropathy, esaxerenone (3 mg/kg), olmesartan (an angiotensin II receptor blocker; 1 mg/kg), or both were orally administered to KK-Ay mice, a type 2 diabetes model, once daily for 56 days. Urinary albumin (Ualb), UACR, and markers, such as podocalyxin, monocyte chemoattractant protein-1 (MCP-1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured, along with systolic blood pressure (SBP), fasting blood glucose, and serum K
Identifiants
pubmed: 32616846
doi: 10.1038/s41440-020-0495-0
pii: 10.1038/s41440-020-0495-0
pmc: PMC7685977
doi:
Substances chimiques
Angiotensin II Type 1 Receptor Blockers
0
Imidazoles
0
Mineralocorticoid Receptor Antagonists
0
Pyrroles
0
Sulfones
0
Tetrazoles
0
olmesartan
8W1IQP3U10
esaxerenone
N62TGJ04A1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1204-1213Références
Keri KC, Samji NS, Blumenthal S. Diabetic nephropathy: newer therapeutic perspectives. J Community Hosp Intern Med Perspect. 2018;8:200–7.
doi: 10.1080/20009666.2018.1500423
Masakane I, Taniguchi M, Nakai S, Tsuchida K, Goto S, Wada A, et al. Annual dialysis data report 2015, JSDT renal data registry. Ren Replacement Ther. 2018;4:19.
doi: 10.1186/s41100-018-0149-8
Braun L, Sood V, Hogue S, Lieberman B, Copley-Merriman C. High burden and unmet patient needs in chronic kidney disease. Int J Nephrol Renovasc Dis. 2012;5:151–63.
pubmed: 23293534
pmcid: 3534533
Giunti S, Barit D, Cooper ME. Mechanisms of diabetic nephropathy: role of hypertension. Hypertension. 2006;48:519–26.
doi: 10.1161/01.HYP.0000240331.32352.0c
Shimamoto K, Ando K, Fujita T, Hasebe N, Higaki J, Horiuchi M, et al. The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2014). Hypertens Res. 2014;37:253–390.
doi: 10.1038/hr.2013.80
Umanath K, Lewis JB. Update on diabetic nephropathy: core curriculum 2018. Am J Kidney Dis. 2018;71:884–95.
doi: 10.1053/j.ajkd.2017.10.026
Arai K, Homma T, Morikawa Y, Ubukata N, Tsuruoka H, Aoki K, et al. Pharmacological profile of CS-3150, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist. Eur J Pharm. 2015;761:226–34.
doi: 10.1016/j.ejphar.2015.06.015
Yamada M, Takei M, Suzuki E, Takakusa H, Kotsuma M, Washio T, et al. Pharmacokinetics, distribution, and disposition of esaxerenone, a novel, highly potent and selective non-steroidal mineralocorticoid receptor antagonist, in rats and monkeys. Xenobiotica. 2017;47:1090–103.
doi: 10.1080/00498254.2016.1263766
Kolkhof P, Bärfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234:T125–40.
doi: 10.1530/JOE-16-0600
Arai K, Tsuruoka H, Homma T. CS-3150, a novel non-steroidal mineralocorticoid receptor antagonist, prevents hypertension and cardiorenal injury in Dahl salt-sensitive hypertensive rats. Eur J Pharm. 2015;769:266–73.
doi: 10.1016/j.ejphar.2015.11.028
Duggan S. Esaxerenone: first global approval. Drugs. 2019;79:477–81.
doi: 10.1007/s40265-019-01073-5
Ito S, Itoh H, Rakugi H, Okuda Y, Yoshimura M, Yamakawa S. Double-blind randomized phase 3 study comparing esaxerenone (CS-3150) and eplerenone in patients with essential hypertension (ESAX-HTN Study). Hypertension. 2020;75:51–8.
doi: 10.1161/HYPERTENSIONAHA.119.13569
Rakugi H, Ito S, Itoh H, Okuda Y, Yamakawa S. Long-term phase 3 study of esaxerenone as mono or combination therapy with other antihypertensive drugs in patients with essential hypertension. Hypertens Res. 2019;42:1932–41.
doi: 10.1038/s41440-019-0314-7
Mavrakanas TA, Gariani K, Martin PY. Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy: a systematic review. Eur J Intern Med. 2014;25:173–6.
doi: 10.1016/j.ejim.2013.11.007
Nishimoto M, Ohtsu H, Marumo T, Kawarazaki W, Ayuzawa N, Ueda K, et al. Mineralocorticoid receptor blockade suppresses dietary salt-induced ACEI/ARB-resistant albuminuria in non-diabetic hypertension: a sub-analysis of evaluate study. Hypertens Res. 2019;42:514–21.
doi: 10.1038/s41440-018-0201-7
Katayama S, Yamada D, Nakayama M, Yamada T, Myoishi M, Kato M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy. J Diabetes Complicat. 2017;31:758–65.
doi: 10.1016/j.jdiacomp.2016.11.021
Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314:884–94.
doi: 10.1001/jama.2015.10081
Ito S, Shikata K, Nangaku M, Okuda Y, Sawanoburi T. Efficacy and safety of esaxerenone (CS-3150) for the treatment of type 2 diabetes with microalbuminuria: A randomized, double-blind, placebo-controlled, phase II trial. Clin J Am Soc Nephrol. 2019;14:1161–72.
doi: 10.2215/CJN.14751218
Itoh H, Ito S, Rakugi H, Okuda Y, Nishioka S. Efficacy and safety of dosage-escalation of low-dosage esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes and albuminuria: a single-arm, open-label study. Hypertension Res. 2019;42:1572–81.
doi: 10.1038/s41440-019-0270-2
Arai K, Morikawa Y, Ubukata N, Tsuruoka H, Homma T. CS-3150, a novel nonsteroidal mineralocorticoid receptor antagonist, shows preventive and therapeutic effects on renal injury in deoxycorticosterone acetate/salt-induced hypertensive rats. J Pharm Exp Ther. 2016;358:548–57.
doi: 10.1124/jpet.116.234765
Li L, Guan Y, Kobori H, Morishita A, Kobara H, Masaki T, et al. Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150), on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats. Hypertension Res. 2019;42:769–78.
doi: 10.1038/s41440-018-0187-1
Okazaki M, Saito Y, Udaka Y, Maruyama M, Murakami H, Ota S, et al. Diabetic nephropathy in KK and KK-Ay mice. Exp Anim. 2002;51:191–6.
doi: 10.1538/expanim.51.191
Bhuiyan AS, Rafiq K, Kobara H, Masaki T, Nakano D, Nishiyama A. Effect of a novel nonsteroidal selective mineralocorticoid receptor antagonist, esaxerenone (CS-3150), on blood pressure and renal injury in high salt-treated type 2 diabetic mice. Hypertens Res. 2019;42:892–902.
doi: 10.1038/s41440-019-0211-0
Takahashi S, Katada J, Daida H, Kitamura F, Yokoyama K. Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis. J Hum Hypertens. 2016;30:534–42.
doi: 10.1038/jhh.2015.119
Tomino Y. Lessons from the KK-Ay mouse, a spontaneous animal model for the treatment of human type 2 diabetic nephropathy. Nephrourol Mon. 2012;4:524–9.
doi: 10.5812/numonthly.1954
Bolignano D, Palmer SC, Navaneethan SD, Strippoli GFM. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;4:CD007004.
Zhou G, Johansson U, Peng XR, Bamberg K, Huang Y. An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice. Am J Transl Res. 2016;8:1339–54.
pubmed: 27186263
pmcid: 4859623
Tesch GH, Young MJ. Mineralocorticoid receptor signaling as a therapeutic target for renal and cardiac fibrosis. Front Pharmacol. 2017;8:313.
doi: 10.3389/fphar.2017.00313
Nishiyama A. Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease. Hypertens Res. 2019;42:293–300.
doi: 10.1038/s41440-018-0158-6
Shibata S, Ishizawa K, Uchida S. Mineralocorticoid receptor as a therapeutic target in chronic kidney disease and hypertension. Hypertens Res. 2017;40:221–5.
doi: 10.1038/hr.2016.137
Dąbrowska N, Wiczkowski A. Analytics of oxidative stress markers in the early diagnosis of oxygen DNA damage. Adv Clin Exp Med. 2017;26:155–66.
doi: 10.17219/acem/43272
Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomolecules. 2015;5:194–222.
doi: 10.3390/biom5010194
Vukadinović D, Lavall D, Vukadinović AN, Pitt B, Wagenpfeil S, Böhm M. True rate of mineralocorticoid receptor antagonists-related hyperkalemia in placebo-controlled trials: a meta-analysis. Am Heart J. 2017;188:99–108.
doi: 10.1016/j.ahj.2017.03.011
Van Buren PN, Adams-Huet B, Nguyen M, Molina C, Toto RD. Potassium handling with dual renin-angiotensin system inhibition in diabetic nephropathy. Clin J Am Soc Nephrol. 2014;9:295–301.
doi: 10.2215/CJN.07460713
Bakris GL, Siomos M, Richardson D, Janssen I, Bolton WK, Hebert L, et al. ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group. Kidney Int. 2000;58:2084–92.
doi: 10.1111/j.1523-1755.2000.00381.x
Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354:131–40.
doi: 10.1056/NEJMoa053107
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.
doi: 10.1056/NEJMoa011303
Sun LJ, Sun YN, Shan JP, Jiang GR. Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy. J Diabetes Investig. 2017;8:609–18.
doi: 10.1111/jdi.12629