Finerenone cardiorenal effects and its placement in treatment of chronic kidney disease in patients with type 2 diabetes mellitus: A review

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Abstract

Chronic kidney disease (CKD) is one of the most common complications of diabetes mellitus and an independent risk factor for cardiovascular disease. Despite guideline-directed therapy of CKD in patients with type 2 diabetes, the risk of renal failure and cardiovascular events still remains high. To date, current medications for CKD haven’t reduced enough the residual risk associated with inflammation and fibrosis in patients with type 2 diabetes. Here, in this review we present the results of FIDELIO-DKD, FIGARO-DKD trials and their pooled analysis FIDELITY, aimed to evaluate the effectiveness and safety of selective non-steroidal mineralocorticoid receptor antagonist finerenone in patients with type 2 diabetes with wide range stages of CKD. Modern pathophysiological aspects of mineralocorticoid receptor hyperactivation and features of their blockade by steroidal and nonsteroidal mineralocorticoid receptor antagonists are considered, differences in pharmacological effects between them are also discussed, finerenone benefits and its adverse events, demonstrated in randomized clinical trials are considered here. The probable mechanisms of early and delayed action of finerenone, which were realized in beneficial cardiovascular and renal outcomes in patients with type 2 diabetes with CKD, are presented here. Practical points for finerenone initiation and titration are indicated, aimed to minimize the hyperkalemia risk. Current guidelines for CKD treatment in patients with type 2 diabetes are analyzed, the finerenone placement in combined nephroprotective therapy is determined.

About the authors

Vladimir V. Salukhov

Kirov Military Medical Academy

Author for correspondence.
Email: vlasaluk@yandex.ru
ORCID iD: 0000-0003-1851-0941

д-р мед. наук, нач. 1-й каф. и клиники (терапии усовершенствования врачей)

Russian Federation, Санкт-Петербург

Minara S. Shamkhalova

Endocrinology Research Centre

Email: shamkhalova@mail.ru
ORCID iD: 0000-0002-3433-0142

д-р мед. наук, проф., зав. отд-нием диабетической болезни почек и посттрансплантационной реабилитации

Russian Federation, Moscow

Alla V. Duganova

Kirov Military Medical Academy

Email: alladuganova1@rambler.ru
ORCID iD: 0000-0002-5726-0845

канд. мед. наук, преподаватель 1-й каф. и клиники (терапии усовершенствования врачей) им. акад. Н.С. Молчанова

Russian Federation, Saint Petersburg

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Supplementary files

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1. JATS XML
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2. Fig. 1. Incidence of cardiovascular and renal combined endpoints (adapted [30]): a – combined cardiovascular endpoint; b – combined renal endpoint.

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3. Fig. 2: a – chronology of the development of the main pathophysiological processes in the hyperactivation of mineralocorticoid receptors, which corrects finereon; b – dynamics of the ratio of albumin to creatinine relative to the initial values; c – the average change in the angle of inclination of the calculated velocity of the globular filtration in the FIDELIO DKD study (adapted [29, 22]).

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4. Fig. 3. Algorithm of initiation of the reception of finerenone and its titration for correction of hyperkalemia (adapted [43, 44]).

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5. Fig. 4. The mechanism of action of finerenon under conditions of pathological hyperactivation of mineralocorticoid receptors (adapted [10, 47]).

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6. Table 1. Fig. 1

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7. Table 1. Fig. 2

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8. Table 1. Fig. 3

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