Novel cardioprotective and nephroprotective combination in patients with type 2 diabetes and chronic kidney disease: perspectives of use
https://doi.org/10.14341/DM13113
Abstract
Chronic kidney disease (CKD) is a common complication of diabetes mellitus. It increases significantly cardiovascular risk and decreases the quality of life. CKD requires treatment, and the treatment paradigm for type 2 diabetes has shifted from a glucose-centric approach towards disease-modifying therapy. Attention is being paid to cardioprotective and nephroprotective effects. In patients with type 2 diabetes and CKD, drugs that affect the renin-angiotensin-aldosterone system, as well as sodium-glucose cotransporter type 2 inhibitors (iSGLT2) are widely used. Despite the proven positive effect of these drugs in preservation of renal functions, the pathogenesis of CKD contains links that have not yet been covered. In particular, the activity of fibrosis processes in the renal parenchyma is increased in patients with CKD due to high expression of mineracorticoid receptors. It may be a potential target for nephroprotective drugs. Thus, mineralocorticoid receptor antagonists (MCRA) may influence the residual risk of CKD progression. In particular, the effectiveness of the non-steroid selective AMCR finerenone has been proven in a number of large clinical studies, which confirmed its nephroprotective potential. In this regard, studies aimed at studying the joint effect of known nephroprotective drugs, as well as their combined effect on cardiovascular risk, are highly needed.
This review marks the main mechanisms of the combined action of iSGLT2 and finerenone. Discussion of the results of main clinical studies with combined use of standard nephroprotective therapy, SGLT2 and finerenone is also presented.
About the Authors
Yu. Sh. KhalimovRussian Federation
Yuri Sh. Khalimov - MD, PhD, Professor.
197022, St-Petersburg, L. Tolstoy st., 17, build. 11
Competing Interests:
Публикация подготовлена при поддержке АО «Байер». Компания «Байер» поддерживала техническую редакцию статьи
G. V. Semikova
Russian Federation
Galina V. Semikova - PhD, Assistant.
6-8 L. Tolstoy street, 197022 St-Petersburg
Competing Interests:
Публикация подготовлена при поддержке АО «Байер». Компания «Байер» поддерживала техническую редакцию статьи
Yu. A. Shutova
Russian Federation
Yulia A. Shutova
St.-Petersburg
Competing Interests:
Публикация подготовлена при поддержке АО «Байер». Компания «Байер» поддерживала техническую редакцию статьи. Ю.А. Шутова является сотрудником АО «Байер»
References
1. Cameron JS. The discovery of diabetic nephropathy: From small print to centre stage. J Nephrol. 2006:19 Suppl 10:S75-87.2006
2. Saran R, Li Y, Robinson B et al. US Renal Data System 2015 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2016;67(3 Suppl 1):Svii, S1-305. https://doi.org/10.1053/j.ajkd.2015.12.014
3. Bonora E, Trombetta M, Dauriz M, et al. Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9. BMJ Open Diabetes Res Care, 2020;8(1):e001549. https://doi.org/10.1136/bmjdrc-2020-001549
4. Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat. Rev. Nephrol. 2016;12(2):73-81. https://doi.org/10.1038/nrneph.2015.173
5. Wu B, Bell K, Stanford A, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns—NHANES 2007–2012. BMJ Open Diab. Res. Care. 2016;4(1):e000154. https://doi.org/10.1136/bmjdrc-2015-000154
6. Dobronravov VA. Epidemiology of diabetic nephropathy: general and regional problems. Nephrology. 2002;6(1):16-22, (In Russ.)]. https://doi.org/10.24884/1561-6274-2002-6-1-16-22
7. Dedov II, Shestakova MV, Suntsov YI, et al. Federal targeted programme “Prevention and management of socially significant diseases (2007–2012)”: results of the “Diabetes mellitus” subprogramme. Diabetes mellitus. 2013;16(2S):1-48. (In Russ.). https://doi.org/10.14341/2072-0351-3879
8. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Diabetes Mellitus.2023;26(S2):1-231. (In Russ.). https://doi.org/10.14341/DM13042
9. Shestakova MV, Shamkhalova MS, Yarek-Martynova IY, et al. Diabetes mellitus and chronic kidney disease: achievements, unresolved problems, and prospects for therapy. Diabetes mellitus. 2011;14(1):81-88. (In Russ.). https://doi.org/10.14341/2072-0351-6254
10. Wheeler DC, James J, Patel D, et al. SGLT2 inhibitors: slowing of chronic kidney disease progression in Type 2 diabetes. Diabetes Ther. 2020;11(12):2757-2774. https://doi.org/10.1007/s13300-020-00930-x
11. de Boer IH, Khunti K, Sadusky T, et al. Diabetes Management in Chronic Kidney Disease: A Consensus Report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2022;102(5):974–989, https://doi.org/10.1016/j.kint.2022.08.012
12. Shestakova MV, Dobronravov VA, Ametov AS, et al. Prospects of finerenone use in Russian population of patients with chronic kidney disease and type 2 diabetes. Resolution of multidisciplinary. Advisory board. Diabetes Mellitus, 2023;26(5):492-499. (In Russ.). https://doi.org/10.14341/DM13020
13. 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(6):474-484, https://doi.org/10.1093/eurheartj/ehab777
14. Marx N, Federici M, Schütt K, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44(39):4043-4140. https://doi.org/10.1093/eurheartj/ehad192
15. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12:2032–2045. https://doi.org/10.2215/CJN.11491116
16. Agarwal R. Pathogenesis of Diabetic Nephropathy. Chronic Kidney Disease and Type 2 Diabetes. 2021;1:2–7. https://doi.org/10.2337/db20211-2
17. Hou YC, Zheng CM, Yen TH, et al. Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection. Int J Mol Sci. 2020;21(21):7833. https://doi.org/10.3390/ijms21217833
18. Lopaschuk GD, Verma S. Mechanisms of Cardiovascular Benefits of Sodium Glucose Co-Transporter 2 (SGLT2) Inhibitors. JACC Basic Transl Sci. 2020;5(6):632-644. https://doi.org/10.1016/j.jacbts.2020.02.004
19. Chertow GM, Vart P, Jongs N, et al. Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease. J Am Soc Nephrol. 2021;32(9):2352-2361. https://doi.org/10.1681/ASN.2021020167
20. Epstein M. Aldosterone and mineralocorticoid receptor signaling as determinants of cardiovascular and renal injury: an extraordinary paradigm shift. Kidney Int Suppl (2011). 2022; 12(1): 1–6. https://doi.org/10.1016/j.kisu.2021.11.007
21. Salukhov VV, Shamkhalova MS, Duganova AV. Finerenone cardiorenal effects and its placement in treatment of chronic kidney disease in patients with type 2 diabetes mellitus: A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(3):261–273. (in Russ.), https://doi.org/10.26442/00403660.2023.03.202152
22. Kolkhof P, Lawatscheck R, Filippatos G, et al. Nonsteroidal Mineralocorticoid Receptor Antagonism by Finerenone-Translational Aspects and Clinical Perspectives across Multiple Organ Systems. Int J Mol Sci. 2022;23(16):9243, https://doi.org/10.3390/ijms23169243
23. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. 2019;380(24):2295-2306. https://doi.org/10.1056/NEJMoa1811744
24. 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. 2021, https://doi.org/10.1093/ndt/gfab336
25. Kolkhof P, Hartmann E, Freyberger A, et al. Effects of Finerenone Combined with Empagliflozin in a Model of Hypertension-Induced End-Organ Damage. Am J Nephrol. 2021;52(8):642-652. https://doi.org/10.1159/000516213
26. Rossing P, Anker SD, Filippatos G, et al. Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis. Diabetes Care. 2022;45(12):2991-2998, https://doi.org/10.2337/dc22-0294
27. Provenzano M, Jongs N, Vart P, et al. The kidney protective effects of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, are present in patients with CKD treated with mineralocorticoid receptor antagonists. Kidney Int Rep. 2021;7(3):436–443, https://doi.org/10.1016/j.ekir.2021.12.013
28. Heerspink HJL, Vart P, Jongs N, et al. Estimated lifetime benefit of novel pharmacological therapies in patients with type 2 diabetes and chronic kidney disease: A joint analysis of randomized controlled clinical trials. Diabetes Obesity and Metabolism, 2023;25(11):3327-3336. https://doi.org/10.1111/dom.15232
29. Naaman SC, Bakris GL. Diabetic Nephropathy: Update on Pillars of Therapy Slowing Progression. Diabetes Care. 2023; 46(9):1574-1586. https://doi.org/10.2337/dci23-0030
30. Neuen BL, Heeerspink HJL, Vart P, et al. Estimated Lifetime Cardiovascular, Kidney and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Non-steroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Circulation. 2023. Ahead of print. https://doi.org/10.1161/CIRCULATIONAHA.123.067584
31. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation, 2022;145(18):e895-e1032. https://doi.org/10.1161/CIR.0000000000001063
32. Desai NR, Navaneethan SD, Nicholas SB, et al. Design and rationale of FINE-REAL: A prospective study of finerenone in clinical practice. J Diabetes Complications. 2023;37(4):108411. https://doi.org/10.1016/j.jdiacomp.2023.108411
33. Vizcaya D, Kovesdy CP, Reyes A, et al. Characteristics of patients with chronic kidney disease and Type 2 diabetes initiating finerenone in the USA: a multi-database, cross-sectional study. J Comp Eff Res. 2023;12(8):e230076, https://doi.org/10.57264/cer-2023-0076
34. Nicholas SB, Correa-Rotter R, Desai N, et al. Interim Results from FINE-REAL: A Prospective Study Providing Insights into the Use of Finerenonein Routine Clinical Settings. Presented on November 2023 ASN Congress. Poster number SA-PO481
35. Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. 2022;145(9):e722-e759, https://doi.org/10.1161/CIR.0000000000001040
36. Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Pland2022 Update. Endocr Pract. 2022;28(10):923-1049, https://doi.org/10.1016/j.eprac.2022.08.002
37. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S): S1-S127. https://doi.org/10.1016/j.kint.2022.06.008
38. ElSayed NA, Aleppo G, Aroda VR, et al. Summary of Revisions: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46 (Suppl 1):S5-S9. https://doi.org/10.2337/dc23-Srev
39. Mancia G, Kreutz R, Brunstrom M, et al. 2023 ESH Guidelines for the management of arterial hypertension. J Hypertens. 2023;41(12):1874-2071. https://doi.org/10.1097/HJH.0000000000003480
40. Sarafidis PA, Iatridi F, Ferro C, et al. Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA), Clinical Kidney Journal. 2023; 16(11): 1885–1907. https://doi.org/10.1093/ckj/sfad139
41. McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023;44(37):3627-3639. https://doi.org/10.1093/eurheartj/ehad195
42. Blazek O, Bakris GL. The evolution of “pillars of therapy” to reduce heart failure risk and slow diabetic kidney disease progression. American Heart Journal Plus. 2022;19. https://doi.org/10.1016/j.ahjo.2022.100187.
43. Wanner C, Fioretto P, Kovesdy CP, et al. Endocrinol Diabetes Metab. 2022;5(6):e360. https://doi.org/10.1002/edm2.360
Supplementary files
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1. Figure 1. Complementary mechanisms of action of sodium-glucose co-transporter type 2 inhibitors and finerenone. | |
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2. Figure 2. Comparative analysis of FIDELIO and CREDENCE results after adjusting for major differences. Adapted from [24]. | |
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3. Figure 3. Effects of treatment with finerenone and sodium-glucose co-transporter type 2 inhibitors in preclinical trials. Adapted from [25]. | |
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4. Figure 4. Cardio-nephroprotective effect of finerenone depending on initial therapy with sodium-glucose co-transporter type 2 inhibitors. Adapted from [26]. | |
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5. Figure 5. Effects of combination disease-modifying therapy for chronic kidney disease (sodium-glucose co-transporter type 2 inhibitors + finerenone + angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers) compared with standard therapy with angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers for key endpoints. Adapted from [28]. | |
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Review
For citations:
Khalimov Yu.Sh., Semikova G.V., Shutova Yu.A. Novel cardioprotective and nephroprotective combination in patients with type 2 diabetes and chronic kidney disease: perspectives of use. Diabetes mellitus. 2024;27(1):93-103. (In Russ.) https://doi.org/10.14341/DM13113

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