Skip to main content

Advertisement

SpringerLink
Log in

The role of a novel mineralocorticoid receptor antagonist, finerenone, in chronic kidney disease: mechanisms and clinical advances

  • Review article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy.

Summary

This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns.

Conclusion

Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jager KJ, Fraser S. The ascending rank of chronic kidney disease in the global burden of disease study. Nephrol Dial Transplant. 2017;32:ii121–8.

    Article  PubMed  Google Scholar 

  2. Webster AC, Nagler EV, Morton RL, Masson P. Chronic kidney disease. Lancet. 2017;389:1238–52.

    Article  PubMed  Google Scholar 

  3. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the global burden of disease study 2017. Lancet. 2020;395:709–33.

  4. Eckardt KU, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet. 2013;382:158–69.

    Article  PubMed  Google Scholar 

  5. Chen TK, Knicely DH, Grams ME. Chronic kidney disease diagnosis and management: a review. JAMA. 2019;322:1294–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yang S, Zhao L, Mi Y, He W. Effects of sodium-glucose cotransporter-2 inhibitors and aldosterone antagonists, in addition to renin-angiotensin system antagonists, on major adverse kidney outcomes in patients with type 2 diabetes and chronic kidney disease: a systematic review and network meta-analysis. Diabetes Obes Metab. 2022;24:2159–68.

    Article  CAS  PubMed  Google Scholar 

  7. Georgianos PI, Agarwal R. Mineralocorticoid receptor antagonism in chronic kidney disease. Kidney Int Rep. 2021;6:2281–91.

    Article  PubMed  PubMed Central  Google Scholar 

  8. van der Aart-van der Beek AB, de Boer RA, Heerspink H. Kidney and heart failure outcomes associated with SGLT2 inhibitor use. Nat Rev Nephrol. 2022;18:294–306.

    Article  PubMed  Google Scholar 

  9. Zhang F, Liu H, Liu D, et al. Effects of RAAS inhibitors in patients with kidney disease. Curr Hypertens Rep. 2017;19:72.

    Article  PubMed  Google Scholar 

  10. Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94–8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7:1385–403.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kolkhof P, Jaisser F, Kim SY, Filippatos G, Nowack C, Pitt B. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: comparison at bench and bedside. Handb Exp Pharmacol. 2017;243:271–305.

    Article  CAS  PubMed  Google Scholar 

  13. Kintscher U, Bakris GL, Kolkhof P. Novel non-steroidal mineralocorticoid receptor antagonists in cardiorenal disease. Br J Pharmacol. 2022;179:3220–34.

    Article  CAS  PubMed  Google Scholar 

  14. Parfianowicz D, Shah S, Nguyen C, et al. Finerenone: a new era for mineralocorticoid receptor antagonism and cardiorenal protection. Curr Probl Cardiol. 2022;47: 101386.

    Article  PubMed  Google Scholar 

  15. Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L, Lombès M. The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology. Nucl Recept Signal. 2007;5: e012.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Funder JW. Minireview: aldosterone and mineralocorticoid receptors: past, present, and future. Endocrinology. 2010;151:5098–102.

    Article  PubMed  Google Scholar 

  17. de Borst MH, Navis G. Sodium intake, RAAS-blockade and progressive renal disease. Pharmacol Res. 2016;107:344–51.

    Article  PubMed  Google Scholar 

  18. Nishiyama A. Pathophysiological mechanisms of mineralocorticoid receptor-dependent cardiovascular and chronic kidney disease. Hypertens Res. 2019;42:293–300.

    Article  CAS  PubMed  Google Scholar 

  19. Verma A, Vaidya A, Subudhi S, Waikar SS. Aldosterone in chronic kidney disease and renal outcomes. Eur Heart J. 2022;43:3781–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brem AS, Morris DJ, Gong R. Aldosterone-induced fibrosis in the kidney: questions and controversies. Am J Kidney Dis. 2011;58:471–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Farman N, Bocchi B. Mineralocorticoid selectivity: molecular and cellular aspects. Kidney Int. 2000;57:1364–9.

    Article  CAS  PubMed  Google Scholar 

  22. Lother A. Mineralocorticoid receptors: master regulators of extracellular matrix remodeling. Circ Res. 2020;127:354–6.

    Article  CAS  PubMed  Google Scholar 

  23. Palacios-Ramirez R, Lima-Posada I, Bonnard B, et al. Mineralocorticoid receptor antagonism prevents the synergistic effect of metabolic challenge and chronic kidney disease on renal fibrosis and inflammation in mice. Front Physiol. 2022;13: 859812.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Qiang P, Hao J, Yang F, et al. Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β1 pathway in mice induced with aldosterone. Front Immunol. 2022;13: 948658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ferreira NS, Tostes RC, Paradis P, Schiffrin EL. Aldosterone, inflammation, immune system, and hypertension. Am J Hypertens. 2021;34:15–27.

    Article  CAS  PubMed  Google Scholar 

  26. Luther JM, Fogo AB. The role of mineralocorticoid receptor activation in kidney inflammation and fibrosis. Kidney Int Suppl. 2011;2022(12):63–8.

    Google Scholar 

  27. Barrera-Chimal J, Jaisser F, Anders HJ. The mineralocorticoid receptor in chronic kidney disease. Br J Pharmacol. 2022;179:3152–64.

    Article  CAS  PubMed  Google Scholar 

  28. Agarwal R, Anker SD, Bakris G, et al. Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone. Nephrol Dial Transplant. 2022;37:1014–23.

    Article  CAS  PubMed  Google Scholar 

  29. Rico-Mesa JS, White A, Ahmadian-Tehrani A, Anderson AS. Mineralocorticoid receptor antagonists: a comprehensive review of finerenone. Curr Cardiol Rep. 2020;22:140.

    Article  PubMed  Google Scholar 

  30. Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37:2105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Filippatos G, Anker SD, Agarwal R, et al. Finerenone and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes. Circulation. 2021;143:540–52.

    Article  CAS  PubMed  Google Scholar 

  32. Lavall D, Jacobs N, Mahfoud F, Kolkhof P, Böhm M, Laufs U. The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. Biochem Pharmacol. 2019;168:173–83.

    Article  CAS  PubMed  Google Scholar 

  33. Luettges K, Bode M, Diemer JN, et al. Finerenone Reduces renal RORγt γδ T cells and protects against cardiorenal damage. Am J Nephrol. 2022;53:552–64.

    Article  CAS  PubMed  Google Scholar 

  34. Gueret A, Harouki N, Favre J, et al. Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction. Hypertension. 2016;67:717–23.

    Article  CAS  PubMed  Google Scholar 

  35. Bonnard B, Pieronne-Deperrois M, Djerada Z, et al. Mineralocorticoid receptor antagonism improves diastolic dysfunction in chronic kidney disease in mice. J Mol Cell Cardiol. 2018;121:124–33.

    Article  CAS  PubMed  Google Scholar 

  36. Brown R, Quirk J, Kirkpatrick P. Eplerenone. Nat Rev Drug Discov. 2003;2:177–8.

    Article  CAS  PubMed  Google Scholar 

  37. Ochs HR, Greenblatt DJ, Bodem G, Smith TW. Spironolactone. Am Heart J. 1978;96:389–400.

    Article  CAS  PubMed  Google Scholar 

  38. Haller H, Bertram A, Stahl K, Menne J. Finerenone: a new mineralocorticoid receptor antagonist without hyperkalemia: an opportunity in patients with CKD. Curr Hypertens Rep. 2016;18:41.

    Article  PubMed  Google Scholar 

  39. Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, Lentini S. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) in individuals with renal impairment. Clin Pharmacol Drug Dev. 2016;5:488–501.

    Article  CAS  PubMed  Google Scholar 

  40. van den Berg P, Ruppert M, Mesic E, et al. Finerenone dose-exposure-response for the primary kidney outcome in FIDELIO-DKD phase III: population pharmacokinetic and time-to-event analysis. Clin Pharmacokinet. 2022;61:439–50.

    Article  PubMed  Google Scholar 

  41. Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, Wensing G. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone-results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30:172–84.

    Article  CAS  PubMed  Google Scholar 

  42. Gerisch M, Heinig R, Engelen A, et al. Biotransformation of finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, in dogs, rats, and humans, In Vivo and In Vitro. Drug Metab Dispos. 2018;46:1546–55.

    Article  CAS  PubMed  Google Scholar 

  43. Cook CS, Berry LM, Bible RH, Hribar JD, Hajdu E, Liu NW. Pharmacokinetics and metabolism of [14C] eplerenone after oral administration to humans. Drug Metab Dispos. 2003;31:1448–55.

    Article  CAS  PubMed  Google Scholar 

  44. Gardiner P, Schrode K, Quinlan D, et al. Spironolactone metabolism: steady-state serum levels of the sulfur-containing metabolites. J Clin Pharmacol. 1989;29:342–7.

    Article  CAS  PubMed  Google Scholar 

  45. Danjuma MI, Mukherjee I, Makaronidis J, Osula S. Converging indications of aldosterone antagonists (spironolactone and eplerenone): a narrative review of safety profiles. Curr Hypertens Rep. 2014;16:414.

    Article  PubMed  Google Scholar 

  46. Lainscak M, Pelliccia F, Rosano G, et al. Safety profile of mineralocorticoid receptor antagonists: spironolactone and eplerenone. Int J Cardiol. 2015;200:25–9.

    Article  PubMed  Google Scholar 

  47. Amazit L, Le Billan F, Kolkhof P, et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J Biol Chem. 2015;290:21876–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Le Billan F, Perrot J, Carceller E, et al. Antagonistic effects of finerenone and spironolactone on the aldosterone-regulated transcriptome of human kidney cells. FASEB J. 2021;35:e21314.

    Article  PubMed  Google Scholar 

  49. González-Blázquez R, Somoza B, Gil-Ortega M, et al. Finerenone attenuates endothelial dysfunction and albuminuria in a chronic kidney disease model by a reduction in oxidative stress. Front Pharmacol. 2018;9:1131.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chung EY, Ruospo M, Natale P, et al. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020;10:CD007004.

    PubMed  Google Scholar 

  51. Goulooze SC, Snelder N, Seelmann A, et al. Finerenone dose-exposure-serum potassium response analysis of FIDELIO-DKD phase III: the role of dosing, titration, and inclusion criteria. Clin Pharmacokinet. 2022;61:451–62.

    Article  CAS  PubMed  Google Scholar 

  52. Mima A. A narrative review of diabetic kidney disease: previous and current evidence-based therapeutic approaches. Adv Ther. 2022;39:3488–500.

    Article  PubMed  Google Scholar 

  53. Yuan Q, Tang B, Zhang C. Signaling pathways of chronic kidney diseases, implications for therapeutics. Signal Transduct Target Ther. 2022;7:182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Epstein M. Considerations for the future: current and future treatment paradigms with mineralocorticoid receptor antagonists-unmet needs and underserved patient cohorts. Kidney Int Suppl. 2011;2022(12):69–75.

    Google Scholar 

  55. Lattenist L, Lechner SM, Messaoudi S, et al. Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury-mediated chronic kidney disease: role of oxidative stress. Hypertension. 2017;69:870–8.

    Article  CAS  PubMed  Google Scholar 

  56. Mansour SG, Puthumana J, Coca SG, Gentry M, Parikh CR. Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review. BMC Nephrol. 2017;18:72.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Droebner K, Pavkovic M, Grundmann M, et al. Direct blood pressure-independent anti-fibrotic effects by the selective nonsteroidal mineralocorticoid receptor antagonist finerenone in progressive models of kidney fibrosis. Am J Nephrol. 2021;52:588–601.

    Article  CAS  PubMed  Google Scholar 

  58. Kuppe C, Ibrahim MM, Kranz J, et al. Decoding myofibroblast origins in human kidney fibrosis. Nature. 2021;589:281–6.

    Article  CAS  PubMed  Google Scholar 

  59. Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int. 2002;62:237–44.

    Article  CAS  PubMed  Google Scholar 

  60. Bolignano D, Donato V, Coppolino G, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008;52:595–605.

    Article  CAS  PubMed  Google Scholar 

  61. Martínez-Martínez E, Buonafine M, Boukhalfa I, et al. Aldosterone target NGAL (Neutrophil gelatinase-associated lipocalin) is involved in cardiac remodeling after myocardial infarction through NFκB pathway. Hypertension. 2017;70:1148–56.

    Article  PubMed  Google Scholar 

  62. Li L, Fu H, Liu Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat Rev Nephrol. 2022;18:545–57.

    Article  CAS  PubMed  Google Scholar 

  63. Chen J, Chen JK, Nagai K, et al. EGFR signaling promotes TGFβ-dependent renal fibrosis. J Am Soc Nephrol. 2012;23:215–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wang Z, Chen JK, Wang SW, Moeckel G, Harris RC. Importance of functional EGF receptors in recovery from acute nephrotoxic injury. J Am Soc Nephrol. 2003;14:3147–54.

    Article  CAS  PubMed  Google Scholar 

  65. Tang J, Liu N, Zhuang S. Role of epidermal growth factor receptor in acute and chronic kidney injury. Kidney Int. 2013;83:804–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tang J, Liu N, Tolbert E, et al. Sustained activation of EGFR triggers renal fibrogenesis after acute kidney injury. Am J Pathol. 2013;183:160–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Mima A. Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res. 2013;2013: 248563.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Mima A, Yasuzawa T, King GL, Ueshima S. Obesity-associated glomerular inflammation increases albuminuria without renal histological changes. FEBS Open Bio. 2018;8:664–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mima A, Qi W, King GL. Implications of treatment that target protective mechanisms against diabetic nephropathy. Semin Nephrol. 2012;32:471–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Komada T, Muruve DA. The role of inflammasomes in kidney disease. Nat Rev Nephrol. 2019;15:501–20.

    Article  PubMed  Google Scholar 

  71. Barrera-Chimal J, Estrela GR, Lechner SM, et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 2018;93:1344–55.

    Article  CAS  PubMed  Google Scholar 

  72. Huang LL, Nikolic-Paterson DJ, Han Y, et al. Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease. J Am Soc Nephrol. 2014;25:2231–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhu Z, Rosenkranz K, Kusunoki Y, et al. Finerenone added to RAS/SGLT2 blockade for CKD in alport syndrome. Results of a randomized controlled trial with Col4a3-/-mice. J Am Soc Nephrol. 2023;34:1513–20.

    Article  PubMed  Google Scholar 

  74. Jerome JR, Deliyanti D, Suphapimol V, Kolkhof P, Wilkinson-Berka JL. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces vascular injury and increases regulatory t-cells: studies in rodents with diabetic and neovascular retinopathy. Int J Mol Sci. 2023;24:2334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Meng XM. Inflammatory mediators and renal fibrosis. Adv Exp Med Biol. 2019;1165:381–406.

    Article  CAS  PubMed  Google Scholar 

  76. Barrera-Chimal J, Rocha L, Amador-Martínez I, et al. Delayed spironolactone administration prevents the transition from acute kidney injury to chronic kidney disease through improving renal inflammation. Nephrol Dial Transplant. 2019;34:794–801.

    Article  CAS  PubMed  Google Scholar 

  77. Gluba-Brzózka A, Franczyk B, Olszewski R, Rysz J. The influence of inflammation on anemia in CKD patients. Int J Mol Sci. 2020;21:725.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Dutzmann J, Musmann RJ, Haertlé M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS ONE. 2017;12: e0184888.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Mima A, Yasuzawa T, Nakamura T, Ueshima S. Linagliptin affects IRS1/Akt signaling and prevents high glucose-induced apoptosis in podocytes. Sci Rep. 2020;10:5775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Mima A, Ohshiro Y, Kitada M, et al. Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int. 2011;79:883–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219–29.

    Article  CAS  PubMed  Google Scholar 

  82. Spoto B, Pisano A, Zoccali C. Insulin resistance in chronic kidney disease: a systematic review. Am J Physiol Renal Physiol. 2016;311:1087–108.

    Article  Google Scholar 

  83. Kochan Z, Szupryczynska N, Malgorzewicz S, Karbowska J. Dietary lipids and dyslipidemia in chronic kidney disease. Nutrients. 2021;13:3138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Emanuelsson F, Nordestgaard BG, Tybjærg-Hansen A, Benn M. Impact of LDL cholesterol on microvascular versus macrovascular disease: a mendelian randomization study. J Am Coll Cardiol. 2019;74:1465–76.

    Article  CAS  PubMed  Google Scholar 

  85. Jin T, Fu X, Liu M, An F. Finerenone attenuates myocardial apoptosis, metabolic disturbance and myocardial fibrosis in type 2 diabetes mellitus. Diabetol Metab Syndr. 2023;15:87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Galindo RJ, Beck RW, Scioscia MF, Umpierrez GE, Tuttle KR. Glycemic monitoring and management in advanced chronic kidney disease. Endocr Rev. 2020;41:756–74.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Hirata A, Maeda N, Hiuge A, et al. Blockade of mineralocorticoid receptor reverses adipocyte dysfunction and insulin resistance in obese mice. Cardiovasc Res. 2009;84:164–72.

    Article  CAS  PubMed  Google Scholar 

  88. Pieronne-Deperrois M, Guéret A, Djerada Z, et al. Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice. ESC Heart Fail. 2021;8:1933–43.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Hager MR, Narla AD, Tannock LR. Dyslipidemia in patients with chronic kidney disease. Rev Endocr Metab Disord. 2017;18:29–40.

    Article  CAS  PubMed  Google Scholar 

  90. Marzolla V, Feraco A, Gorini S, et al. The novel non-steroidal MR antagonist finerenone improves metabolic parameters in high-fat diet-fed mice and activates brown adipose tissue via AMPK-ATGL pathway. FASEB J. 2020;34:12450–65.

    Article  CAS  PubMed  Google Scholar 

  91. Marzolla V, Feraco A, Limana F, Kolkhof P, Armani A, Caprio M. Class-specific responses of brown adipose tissue to steroidal and nonsteroidal mineralocorticoid receptor antagonists. J Endocrinol Invest. 2022;45:215–20.

    Article  CAS  PubMed  Google Scholar 

  92. Theofilis P, Vordoni A, Kalaitzidis RG. Oxidative stress management in cardiorenal diseases: focus on novel antidiabetic agents, finerenone, and melatonin. Life (Basel). 2022;12:1663.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Liu C, Yang M, Li L, et al. A glimpse of inflammation and anti-inflammation therapy in diabetic kidney disease. Front Physiol. 2022;13: 909569.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Barrera-Chimal J, André-Grégoire G, Nguyen Dinh Cat A, et al. Benefit of mineralocorticoid receptor antagonism in AKI: role of vascular smooth muscle rac1. J Am Soc Nephrol. 2017;28:1216–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34:2453–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pitt B, Anker SD, Böhm M, et al. Rationale and design of mineralocorticoid receptor antagonist tolerability study-heart failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail. 2015;17:224–32.

    Article  CAS  PubMed  Google Scholar 

  97. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314:884–94.

    Article  CAS  PubMed  Google Scholar 

  98. Agarwal R, Ruilope LM, Ruiz-Hurtado G, et al. Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes. J Hypertens. 2023;41:295–302.

    Article  CAS  PubMed  Google Scholar 

  99. Zhu Y, Song M, Chen T, Yang Z, Liu Y. Effect of finerenone on cardiovascular events in kidney disease and/or diabetes: a meta analysis of randomized control trials. Int Urol Nephrol. 2023;55:1373–81.

    Article  CAS  PubMed  Google Scholar 

  100. Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385:2252–63.

    Article  CAS  PubMed  Google Scholar 

  101. Rossing P, Anker SD, Filippatos G, et al. The impact of obesity on cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes treated with finerenone: post hoc analysis of the FIDELITY study. Diabetes Obes Metab. 2023;25:2989–98.

    Article  CAS  PubMed  Google Scholar 

  102. Major RW, Cheng M, Grant RA, et al. Cardiovascular disease risk factors in chronic kidney disease: a systematic review and meta-analysis. PLoS ONE. 2018;13: e0192895.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43:474–84.

    Article  CAS  PubMed  Google Scholar 

  104. Filippatos G, Bakris GL, Pitt B, et al. Finerenone reduces new-onset atrial fibrillation in patients with chronic kidney disease and type 2 diabetes. J Am Coll Cardiol. 2021;78:142–52.

    Article  CAS  PubMed  Google Scholar 

  105. Filippatos G, Anker SD, August P, et al. Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a FIDELITY analysis. Eur Heart J Cardiovasc Pharmacother. 2023;9:183–91.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64:69–78.

    Article  CAS  PubMed  Google Scholar 

  107. Agarwal R, Joseph A, Anker SD, et al. Hyperkalemia risk with finerenone: results from the FIDELIO-DKD trial. J Am Soc Nephrol. 2022;33:225–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Weir MR, Bakris GL, Bushinsky DA, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372:211–21.

    Article  PubMed  Google Scholar 

  109. Packham DK, Rasmussen HS, Lavin PT, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372:222–31.

    Article  PubMed  Google Scholar 

  110. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;99:S1–S87.

  111. DeFronzo RA, Bakris GL. Modifying chronic kidney disease progression with the mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes. Diabetes Obes Metab. 2022;24:1197–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Mima A. Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease. J Diabetes Complicat. 2018;32:720–5.

    Article  Google Scholar 

  113. Mima A. Sodium-glucose cotransporter 2 inhibitors in patients with non-diabetic chronic kidney disease. Adv Ther. 2021;38:2201–12.

    Article  CAS  PubMed  Google Scholar 

  114. Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388:117–27.

    Article  CAS  PubMed  Google Scholar 

  115. McGuire DK, Shih WJ, Cosentino F, et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021;6:148–58.

    Article  PubMed  Google Scholar 

  116. Barrera-Chimal J, Bonnard B, Jaisser F. Roles of mineralocorticoid receptors in cardiovascular and cardiorenal diseases. Annu Rev Physiol. 2022;84:585–610.

    Article  CAS  PubMed  Google Scholar 

  117. Agarwal R, Anker SD, Filippatos G, et al. Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrol Dial Transplant. 2022;37:1261–9.

    Article  CAS  PubMed  Google Scholar 

  118. Rossing P, Agarwal R, Anker SD, et al. Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: a subgroup analysis from the FIDELIO-DKD trial. Diabetes Obes Metab. 2022;24:125–34.

    Article  CAS  PubMed  Google Scholar 

  119. Rossing P, Agarwal R, Anker SD, et al. Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use. Diabetes Obes Metab. 2023;25:407–16.

    Article  CAS  PubMed  Google Scholar 

  120. Barrera-Chimal J, Lima-Posada I, Bakris GL, Jaisser F. Mineralocorticoid receptor antagonists in diabetic kidney disease-mechanistic and therapeutic effects. Nat Rev Nephrol. 2022;18:56–70.

    Article  CAS  PubMed  Google Scholar 

  121. Yao L, Liang X, Wang P. Therapeutic perspective: evolving evidence of nonsteroidal mineralocorticoid receptor antagonists in diabetic kidney disease. Am J Physiol Endocrinol Metab. 2023;324:531–41.

    Article  Google Scholar 

  122. Heerspink H, Jongs N, Neuen BL, et al. Effects of newer kidney protective agents on kidney endpoints provide implications for future clinical trials. Kidney Int. 2023;104:181–8.

    Article  CAS  PubMed  Google Scholar 

  123. Tu L, Thuillet R, Perrot J, et al. Mineralocorticoid receptor antagonism by finerenone attenuates established pulmonary hypertension in rats. Hypertension. 2022;79:2262–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (82170865) and Taishan Scholars Project of Shandong Province (tsqn202211365).

Author information

Author notes

  1. Xinping Chen and Xuan Li have contributed equally to this article (co-first author).

Authors and Affiliations

  1. Department of Nephrology, Affiliated Hospital of Weifang Medical University, Weifang, 261031, China

    Xinping Chen, Xuan Li, Kexin Lian & Zhentao Guo

  2. Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, 261031, China

    Xinping Chen, Xuan Li, Chengxia Kan, Jingwen Zhang, Xiaodong Sun & Zhentao Guo

  3. Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, 2428 Yuhe Road, Weifang, 261031, China

    Xinping Chen, Kexin Zhang, Wenqiang Zhang, Yixin Song, Chengxia Kan, Jingwen Zhang, Fang Han & Xiaodong Sun

  4. Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, 261031, China

    Wenqiang Zhang & Fang Han

Authors
  1. Xinping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kexin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kexin Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenqiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yixin Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chengxia Kan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jingwen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fang Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiaodong Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhentao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CX and LX were responsible for conceptualization, methodology, data curation, and writing—original draft preparation; GZ and SX were responsible for conceptualization, supervision, writing—reviewing and editing; others were responsible for data curation and investigation.

Corresponding authors

Correspondence to Xiaodong Sun or Zhentao Guo.

Ethics declarations

Conflict of interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, X., Li, X., Zhang, K. et al. The role of a novel mineralocorticoid receptor antagonist, finerenone, in chronic kidney disease: mechanisms and clinical advances. Clin Exp Nephrol 28, 125–135 (2024). https://doi.org/10.1007/s10157-023-02413-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-023-02413-2

Keywords

Search

Navigation