OBJECTIVE: Finerenone, a non-steroidal mineralocorticoid receptor antagonist, improved kidney, and cardiovascular outcomes in patients with CKD and T2D in two Phase 3 outcome trials. The FIND-CKD study investigates the effect of finerenone in adults with CKD without diabetes.
METHODS: FIND-CKD (NCT05047263 and EU CT 2023-506897-11-00) is a randomized, double-blind, placebo-controlled Phase 3 trial in patients with CKD of non-diabetic aetiology. Adults with a urinary albumin-creatinine ratio (UACR) of ≥ 200 to ≤3500 mg/g and eGFR ≥ 25 to <90 mL/min/1.73 m2 receiving a maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor were randomized 1:1 to once daily placebo or finerenone 10 or 20 mg depending on eGFR above or below 60 mL/min/1.73 m2. The primary efficacy outcome is total eGFR slope, defined as the mean annual rate of change in eGFR from baseline to Month 32. Secondary efficacy outcomes include a combined cardiorenal composite outcome comprising time to kidney failure, sustained ≥57% decrease in eGFR, hospitalization for heart failure, or cardiovascular death, as well as separate kidney and cardiovascular composite outcomes. Adverse events are recorded to assess tolerability and safety.
RESULTS: Across 24 countries, 3231 patients were screened and 1584 were randomized to study treatment. The most common causes of CKD were chronic glomerulonephritis (57.0%) and hypertensive/ischaemic nephropathy (29.0%). Immunoglobulin A nephropathy was the most common glomerulonephritis (26.3% of the total population). At baseline, mean eGFR and median UACR were 46.7 mL/min/1.73 m2 and 818.9 mg/g, respectively. Diuretics were used by 282 participants (17.8%), statins by 851 (53.7%), and calcium channel blockers by 794 (50.1%). SGLT2 inhibitors were used in 16.9% of patients; these individuals had a similar mean eGFR (45.6 vs 46.8 mL/min/1.73 m2) and slightly higher median UACR (871.9 vs 808.3 mg/g) compared to those not using SGLT2 inhibitors at baseline.
CONCLUSIONS: FIND-CKD is the first Phase 3 trial of finerenone in patients with CKD of non-diabetic aetiology.

Diabetic kidney disease (DKD) is a common disorder with numerous severe clinical implications. Due to a high level of fibrosis and inflammation that contributes to renal and cardiovascular disease (CVD), existing treatments have not effectively mitigated residual risk for patients with DKD. Excess activation of mineralocorticoid receptors (MRs) plays a significant role in the progression of renal and CVD, mostly by stimulating fibrosis and inflammation. However, the application of traditional steroidal MR antagonists (MRAs) to DKD has been limited by adverse events. Finerenone (FIN), a third-generation non-steroidal selective MRA, has revealed anti-fibrotic and anti-inflammatory effects in pre-clinical studies. Current clinical trials, such as FIDELIO-DKD and FIGARO-DKD and their combined analysis FIDELITY, have elucidated that FIN reduces the kidney and CV composite outcomes and risk of hyperkalemia compared to traditional steroidal MRAs in patients with DKD. As a result, FIN should be regarded as one of the mainstays of treatment for patients with DKD. In this review, the safety, efficiency, and potential mechanisms of FIN treatment on the renal system in patients with DKD is reviewed.

The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal diseases. This meta-analysis assesses the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD). A comprehensive search of PubMed, Embase, and Google Scholar databases was performed to identify relevant randomized controlled trials (RCTs). To quantify the effects of finerenone, the analysis included the estimation of aggregated mean differences (MDs) and relative risks (RRs), as well as 95% confidence intervals (CIs). This meta-analysis included seven double-blind trials with patients suffering from chronic kidney disease (CKD) and T2D. Participants received finerenone or a placebo was assigned at random. The primary efficacy outcomes were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, kidney failure, a sustained 57% decrease in the estimated glomerular filtration rate from baseline over four weeks, or renal death. Among the 39,995 patients included in the analysis, finerenone treatment was associated with a lower risk of cardiovascular and renal-related mortality compared to placebo (RR = 0.86 (0.80, 0.93), p = 0.0002; I-squared statistic (I2 ) = 0%) and (RR = 0.56 (0.17, 1.82), p = 0.34; I2 = 0%). In addition, finerenone treatment was associated with a marginally reduced risk of serious adverse events (RR = 0.95 (0.92, 0.97), p = 0.0001; I2 = 0%), although no significant difference in the overall risk of adverse events was observed between the two groups (RR = 1.00 (0.99, 1.01), p = 0.56; I2 = 0%). This study\'s findings suggest that finerenone administration can reduce the risk of end-stage kidney disease, renal failure, cardiovascular mortality, and hospitalization. Patients with both T2DM and CKD are therefore advised to consider finerenone therapy.

Inappropriate mineralocorticoid receptor (MR) activation in different cardiovascular cell types has deleterious effects on cardiac remodeling and function. Therefore, MR inhibition is a crucial pharmacological strategy to overcome cardiovascular dysfunction. Despite efficient blockade of MR with steroidal MR antagonists (MRAs), their clinical application is unsatisfactory due to the adverse effects. Newer non-steroidal MRAs with greater potency could be suitable for clinical application, especially in patients with type 2 diabetes mellitus and chronic kidney disease. Although clinical evidence has shown the beneficial effects of non-steroidal MRAs on cardiovascular outcomes in patients with heart failure with reduced ejection fraction, clinical trials are ongoing to evaluate the efficacy of heart failure with preserved ejection fraction. Therefore, comparative pharmacological characterization of non-steroidal MRAs over classic steroidal MRAs is crucial. Here, we summarize the pre-clinical evidence of non-steroidal MRAs, which suggests an improvement in cardiac dysfunction, as well as the underlying molecular mechanisms in animal models mimicking different clinical conditions. In addition, we discuss up-to-date information from clinical trials regarding the beneficial effects of non-steroidal MRAs on meaningful cardiovascular outcomes. Both pre-clinical and clinical evidence support treatment with non-steroidal MRAs in patients with cardiovascular disease.