Finerenone Makes A Big Difference in The Treatment Of T2D-related CKD

The prevalence of chronic kidney disease (CKD) has been rising in my country in recent years. According to the 2019 Global Burden of Disease (GBD) data, the prevalence of CKD in my country is 10.6%, corresponding to a huge patient population of nearly 150 million. The disease burden is heavy. Among the specific causes of CKD, the proportion of type 2 diabetes (T2D) has risen rapidly [1]. Some studies estimate that since 2011, T2D-related CKD has surpassed glomerulonephritis, and has become the first hospitalization of CKD patients in my country. Etiology [2].

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T2D-related CKD will not only lead to the gradual deterioration of renal function in patients, and even develop the end-stage renal disease (ESRD), requiring dialysis to maintain life, but also suggest that patients have a higher risk of cardiovascular disease (CVD). Therefore, patients with T2D-related CKD are faced with a "Double attack of the kidney and the heart", and at the same time, the awareness rate of T2D and CKD diagnosis and treatment of Chinese patients is not ideal, which further affects the status quo of disease management and control. Effective therapeutic drugs are urgently needed in clinical practice, which will benefit patients significantly.

On June 28, 2022, the National Medical Products Administration (NMPA) officially approved the new non-steroidal, highly selective mineralocorticoid receptor antagonist (MRA) Finerenone Tablets to be launched in my country for the treatment of T2D-related diseases. Adult patients with CKD [estimated glomerular filtration rate (eGFR) ≥ 25 to < 75 mL/min/1.73m2, with albuminuria] can reduce the risk of sustained decline in eGFR and ESRD. Recently, experts in the field of nephrology in many parts of the country have issued prescriptions one after another, marking the official entry of finerenone into clinical practice and benefiting the majority of T2D-related CKD patients in my country.

Directly hitting the key pathway of the disease, finerenone provides a new dimension of treatment

The pathological mechanism of T2D-related CKD is relatively complicated. The traditional concept believes that abnormal renal hemodynamics and abnormal glucose and lipid metabolism are the two basic pathological mechanisms. Therefore, the previous treatment mainly focuses on the control of blood pressure, blood sugar, blood lipids, and other indicators, such as the use of RAS Antagonists and various hypoglycemic drugs, but patients still have a high risk of CKD and CVD. Even if blood glucose, blood pressure, and other indicators are achieved through comprehensive management, the occurrence and development of CKD cannot be prevented entirely [3].

This means that there are other pathological mechanisms involved in the occurrence of T2D-related CKD, among which the pro-inflammatory and pro-fibrotic effects mediated by mineralocorticoid receptor (MR) overactivation are a key link in the progression of renal disease[4]. As a non-steroidal MRA drug, the onset mechanism of finerenone is to attack the overactivated MR directly and effectively exert anti-inflammatory and anti-fibrosis effects. Compared with traditional treatment methods, finerenone is a new dimension. Intervention in T2D-related CKD provides an important treatment option for patients.

Compared with traditional steroidal MRA such as spironolactone and eplerenone, finerenone has a blocky three-dimensional structure, which has a stronger binding effect on MR, higher selectivity, and no adverse reactions related to sex hormones; at the same time, finerenone Ketones are evenly distributed in the kidney and heart. In terms of pharmacokinetics, its half-life is short and its inactive metabolites, while taking into account the dual benefits of the kidney and heart, the incidence of hyperkalemia is lower[5].

Evidence-based medicine evidence is clear, finerenone is promising for Chinese patients

The innovative mechanism of action of finerenone has laid a theoretical foundation for its clear kidney and heart benefits, and the global key phase III randomized controlled studies FIDELIO, FIGARO, and the pooled analysis of the two FIDELITY studies[6] were included More than 13,000 CKD patients of different stages have fully confirmed the dual benefits and safety of finerenone, including more than 3,000 Asian patients, and there are also positive contributions from Chinese patients and researchers.

The FIDELIO China subgroup analysis evaluated the efficacy and safety of 372 Chinese patients with T2D-related CKD in the study. The results showed that finerenone can reduce the main renal composite endpoints (kidney failure, eGFR decrease ≥ 40% compared with baseline) of Chinese patients. % or kidney disease-related death) the risk was significantly reduced by 41% compared with the placebo group (RRR=0.59, P=0.009), and the benefits of patients in each subgroup were generally consistent.

In terms of secondary cardiovascular composite endpoints, the value of the finerenone treatment group was 25% lower than that of the placebo group (HR=0.75, P=0.408; for the global population, HR=0.86, the risk was significantly reduced by 14%, P=0.03 ), suggesting that Chinese patients receiving finerenone may obtain more significant renal and cardiac benefits; and the safety of finerenone treatment is good, and the incidence of adverse events is the same as that of the placebo group[7].

A series of relevant authoritative guidelines at home and abroad have been updated in recent years, such as "2021 Guidelines for Clinical Diagnosis and Treatment of Diabetic Kidney Disease in China", "2022 American Diabetes Association (ADA) Medical Diagnosis and Treatment Standards for Diabetes", and the 2022 edition of Improving Kidney Disease Outcomes Global Organization (KDIGO) " Based on the high-quality evidence-based medical evidence provided by the above-mentioned studies, the Clinical Practice Guidelines for the Management of Diabetes in Patients with Chronic Kidney Disease, etc., highly recommend the use of finerenone [8-10].

Stepping into Chinese clinical practice, what points should be paid attention to in the application of finerenone?

In terms of specific usage, clinicians can choose the starting dose of finerenone according to the eGFR level:

For patients with eGFR≥60ml/min/1.73m2, start directly with 20mg;

For patients with eGFR ≥ 25 to < 60ml/min/1.73m2, start with 10mg; if the blood potassium level is normal, increase the dose to 20mg within 4 weeks;

Once a day, orally administered.

The approval and clinical practice of finerenone, which uses innovative mechanisms as a winning strategy and escorts patients with excellent evidence, is a milestone event in the treatment of T2D-related CKD diseases in my country and will promote the overall treatment of kidney diseases The field opens a new era! At the same time, it is expected that finerenone will accumulate more data on Chinese patients, provide more guidelines for clinical medication, and benefit the majority of Chinese patients.

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