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14-08-2024 | Finerenone | Review

Finerenone and diabetic renal disease: a narrative review

Authors: Kirthika Venkatesan, Mabel Mary James Cheryeth, Anna Tintu Verghese, Arpita Mariam Mathews, Nikitha Ravisankar, Parvathy Unnikrishnan, Vishakh Prakash, Hridya Harimohan, Nisha Nigil Haroon, Sandra James, Somy Cherian

Published in: Endocrine | Issue 3/2024

Abstract

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor (MR) antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (also known as Kerendia) is more potent than spironolactone in reducing the progression of CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate (GFR) if taken alone or in combination with sodium-glucose transporter 2 inhibitors (SGLT2i). Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this narrative review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes.

R. Agarwal, G. Filippatos, B. Pitt, S.D. Anker, P. Rossing, A. Joseph, P. Kolkhof, C. Nowack, M. Gebel, L.M. Ruilope, G.L. Bakris; FIDELIO-DKD and FIGARO-DKD investigators, Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: he FIDELITY pooled analysis. Eur. Heart J. 43(6), 474–484 (2022). https://doi.org/10.1093/eurheartj/ehab777CrossRefPubMed

Centers for Disease Control and Prevention (CDC). Diabetes and Chronic Kidney Disease. Retrieved from https://www.cdc.gov/diabetes/managing/diabetes-kidney-disease.html#:~:text=CKD%20is%20common%20in%20people,diabetes%20can%20cause%20kidney%20disease (2023)

H. Li, W. Lu, A. Wang, H. Jiang, J. Lyu, Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: Estimates from Global Burden of Disease 2017. J. Diab. Investig. 12(3), 346–356 (2021). https://doi.org/10.1111/jdi.13355CrossRef

A. Makhlough, Z. Kashi, O. Akha, E. Zaboli, J. Yazdanicharati, Effect of spironolactone on diabetic nephropathy compared to the combination of spironolactone and losartan. Nephro-Urol. Monthly 6(1), e12148 (2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968951/

D. Kawanami, Y. Takashi, Y. Muta, N. Oda, D. Nagata, H. Takahashi, M. Tanabe, Mineralocorticoid receptor antagonists in diabetic kidney disease. Front. Pharmacol. 12, 754239 (2021. https://www.frontiersin.org/articles/10.3389/fphar.2021.754239/fullCrossRefPubMedPubMedCentral

Bayer. Product monograph including patient medication information KERENDIA Finerenone tablets Tablets, 10 mg and 20 mg finerenone, Oral Aldosterone Antagonist. Retrieved from https://www.bayer.com/sites/default/files/kerendia-pm-en.pdf. (2022).

T. Iwahana, Y. Saito, S. Okada, H. Kato, R. Ono, Y. Kobayashi, Safety and efficacy of esaxerenone in Japanese hypertensive patients with heart failure with reduced ejection fraction: A retrospective study. PLOS ONE 16(11), e0259485 (2021). https://doi.org/10.1371/journal.pone.0259485CrossRefPubMedPubMedCentral

R. Agarwal, P. Kolkhof, G. Bakris, J. Bauersachs, H. Haller, T. Wada, F. Zannad, Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur. Heart J. 42(2), 152–161 (2021). https://doi.org/10.1093/eurheartj/ehaa736CrossRefPubMed

R.A. DeFronzo, G.L. Bakris, Modifying chronic kidney disease progression with the mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes. Diab. Obes. Metab. 24(7), 1197–1205 (2022). https://doi.org/10.1111/dom.14696CrossRef

10.

M. Epstein, Aldosterone and mineralocorticoid receptor signaling as determinants of cardiovascular and renal injury: From Hans Selye to the present. Am. J. Nephrol. 52(3), 209–216 (2021). https://doi.org/10.1159/000515622CrossRefPubMed

11.

P. Kolkhof, L. Bärfacker, 30 Years of the mineralocorticoid receptor: Mineralocorticoid receptor antagonists: 60 years of research and development. J. Endocrinol. 234(1), T125–T140 (2017). https://doi.org/10.1530/JOE-16-0600CrossRefPubMedPubMedCentral

12.

A. Chaudhuri, H. Ghanim, P. Arora, Improving the residual risk of renal and cardiovascular outcomes in diabetic kidney disease: A review of pathophysiology, mechanisms, and evidence from recent trials. Diab. Obes. Metab. 24(3), 365–376 (2022). https://doi.org/10.1111/dom.14601CrossRef

13.

P. Kolkhof, S.A. Borden, Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics. Mol. Cell. Endocrinol. 350(2), 310–317 (2012). https://doi.org/10.1016/j.mce.2011.06.025CrossRefPubMed

14.

L. Amazit, F.L. Billan, P. Kolkhof et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J. Biol. Chem. 290(36), 21876–21889 (2015). https://doi.org/10.1074/jbc.M115.657957CrossRefPubMedPubMedCentral

15.

G.L. Bakris, R. Agarwal, S.D. Anker, B. Pitt, L.M. Ruilope, P. Rossing, G. Filippatos, Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N. Engl. J. Med. 383(23), 2219–2229 (2020). https://doi.org/10.1056/nejmoa2025845CrossRefPubMed

16.

R. Agarwal, A. Joseph, S.D. Anker, G. Filippatos, P. Rossing, L.M. Ruilope, B. Pitt, P. Kolkhof, C. Scott, R. Lawatscheck, D.J. Wilson, G.L. Bakris; FIDELIO-DKD Investigators, Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial. J. Am. Soc. Nephrology: JASN 33(1), 225–237 (2022). https://doi.org/10.1681/ASN.2021070942CrossRefPubMedPubMedCentral

17.

S.C. Goulooze, N. Snelder, A. Seelmann, A. Horvat-Broecker, M. Brinker, A. Joseph, D. Garmann, J. Lippert, T. Eissing, Finerenone Dose-Exposure-Serum Potassium Response Analysis of FIDELIO-DKD Phase III: The Role of Dosing, Titration, and Inclusion Criteria. Clin. Pharmacokinetics 61(3), 451–462 (2022). https://doi.org/10.1007/s40262-021-01083-1CrossRef

18.

A.D.S. Chaves, N.S. Magalhães, D.B.R. Insuela, P.M.R.E. Silva, M.A. Martins, V.F. Carvalho, Effect of the renin-angiotensin system on the exacerbation of adrenal glucocorticoid steroidogenesis in diabetic mice: Role of angiotensin-II type 2 receptor. Front. Endocrinol. 13, 1040040 (2022. https://www.frontiersin.org/articles/10.3389/fendo.2022.1040040/fullCrossRef

19.

J.M. Brown, M.O. Wijkman, B.L. Claggett, A.M. Shah, C.M. Ballantyne, J. Coresh, S.D. Solomon, Cardiac structure and function across the spectrum of aldosteronism: the atherosclerosis risk in communities study. Hypertension 79(9), 1984–1993 (2022. https://www.ahajournals.org/doi/abs/10.1161/HYPERTENSIONAHA.122.19134CrossRefPubMed

20.

P. Kolkhof, M. Delbeck, A. Kretschmer, W. Steinke, E. Hartmann, L. Bärfacker, S. Schäfer, Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J. Cardiovascular Pharmacol. 64(1), 69–78 (2014. https://journals.lww.com/cardiovascularpharm/FullText/2014/07000/Finerenone,_a_Novel_Selective_Nonsteroidal.11.aspxCrossRef

21.

J. Barrera-Chimal, G.R. Estrela, S.M. Lechner, S. Giraud, S. El Moghrabi, S. Kaaki, F. Jaisser, The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 93, 1344–1355 (2018. https://www.sciencedirect.com/science/article/pii/S0085253818300607CrossRefPubMed

22.

P. Kolkhof, E. Hartmann, A. Freyberger, M. Pavkovic, I. Mathar, P. Sandner, F. Eitner, Effects of finerenone combined with empagliflozin in a model of hypertension-induced end-organ damage. Am. J. Nephrol. 52(8), 642–652 (2021. https://karger.com/ajn/article/52/8/642/827352CrossRefPubMed

23.

B. Pitt, G. Filippatos, R. Agarwal, S.D. Anker, G.L. Bakris, P. Rossing, L.M. Ruilope, Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N. Engl. J. Med. 385(24), 2252–2263 (2021). https://doi.org/10.1056/nejmoa2110956CrossRefPubMed

24.

A.K. Singh, A. Singh, R. Singh, A. Misra, Finerenone in diabetic kidney disease: A systematic review and critical appraisal. Diab. Metab. Syndr. 16(10), 102638 (2022). https://doi.org/10.1016/j.dsx.2022.102638CrossRef

25.

G. Filippatos, S.D. Anker, R. Agarwal, L.M. Ruilope, P. Rossing, G.L. Bakris, C. Tasto, A. Joseph, P. Kolkhof, A. Lage, B. Pitt; FIGARO-DKD Investigators, Finerenone reduces risk of incident heart failure in patients with chronic kidney disease and type 2 diabetes: Analyses from the FIGARO-DKD trial. Circulation 145(6), 437–447 (2022). https://doi.org/10.1161/circulationaha.121.057983CrossRefPubMed

26.

J.B. Green, A.K. Mottl, G. Bakris, H.J.L. Heerspink, J.F.E. Mann, J.B. McGill, M. Nangaku, P. Rossing, C. Scott, A. Gay, R. Agarwal, Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE). Nephrol. Dialysis Transpl. 38(4), 894–903 (2023). https://doi.org/10.1093/ndt/gfac198CrossRef

27.

Kerendia prices, coupons, Copay & Patient Assistance. Drugs.com. (n.d.). https://www.drugs.com/price-guide/kerendia

28.

Cadth reimbursement recommendation Finerenone (Kerendia). https://www.cadth.ca/sites/default/files

29.

P. Rossing, E. Burgess, R. Agarwal, S.D. Anker, G. Filippatos, B. Pitt et al. Finerenone in patients with chronic kidney disease and type 2 diabetes according to baseline HbA1c and insulin use: An analysis from the FIDELIO-DKD study. Diab. Care 45(4), 888–897 (2022). https://doi.org/10.2337/dc21-1944CrossRef

30.

C. Ibuki, H. Kawamata, Y. Seino, K. Mizuno, Successful blood pressure control with additive administration of eplerenone, an aldosterone receptor blocker, in a patient with bilateral renovascular hypertension treated with angioplasty. Intern. Med. 49(22), 2455–2459 (2010). https://www.jstage.jst.go.jp/article/internalmedicine/49/22/49_22_2455/_article/-char/ja/CrossRefPubMed

31.

F. Piccirillo, P. Liporace, A. Nusca, V. Nafisio, A. Corlianò, F. Magarò, F. Grigioni, Effects of finerenone on cardiovascular and chronic kidney diseases: A new weapon against cardiorenal morbidity and mortality—a comprehensive review. J. Cardiovascular Dev. Dis. 10(6), 236 (2023). https://www.mdpi.com/2308-3425/10/6/236CrossRef

Title: Finerenone and diabetic renal disease: a narrative review
Authors: Kirthika Venkatesan
Mabel Mary James Cheryeth
Anna Tintu Verghese
Arpita Mariam Mathews
Nikitha Ravisankar
Parvathy Unnikrishnan
Vishakh Prakash
Hridya Harimohan
Nisha Nigil Haroon
Sandra James
Somy Cherian
Publication date: 14-08-2024
Publisher: Springer US
Keywords: Finerenone
Type 2 Diabetes
Chronic Kidney Disease
Hyperkalemia
Spironolactone
Heart Failure
Eplerenon
Gynecomastia
Published in: Endocrine / Issue 3/2024
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-024-03945-7

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