Early Safety and Efficacy of Initiating Finerenone in Patients with T2D-Related CKD Under Different Combination Regimens with SGLT2i/RASi: A Single-Center, Retrospective, Observational Real-World Study in China

This study aimed to evaluate the early antiproteinuric efficacy and safety of initiating finerenone in patients with type 2 diabetes-related chronic kidney disease (CKD) in a real-world Chinese setting, with a focus on analyzing factors influencing the early decline in estimated glomerular filtration rate (eGFR), regardless of concomitant use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) or renin-angiotensin system inhibitors (RASi).

Patients clinically diagnosed with T2D-related CKD who newly initiated finerenone between March 2023 and February 2024 in the outpatient or inpatient departments of the Department of Nephrology, Zhongshan Hospital, Fudan University, were retrospectively enrolled. All patients were followed up for at least one time point at 4, 8, and 12 weeks after finerenone initiation via electronic medical record review. Urinary albumin-to-creatinine ratio (UACR), 24-hour urine protein (24H-UP), serum creatinine, and potassium levels were recorded at enrollment and each follow-up. eGFR was calculated using the CKD-EPI creatinine equation. The impact of different combination therapy types (SGLT2i/RASi) and baseline eGFR levels on follow-up outcomes was assessed.

A total of 105 patients were enrolled (mean age 59.4 ± 13.3 years, 81 males, 24 females). Eighty-seven patients (82.9%) were diagnosed with type 2 diabetic kidney disease, and 18 (17.1%) were diagnosed with type 2 diabetes complicated by CKD. During the 12 weeks after initiating finerenone, the maximum reduction in UACR was 39.55% (see Supplementary Table 1). This effect was consistent across all treatment groups, irrespective of baseline eGFR levels or concomitant use of SGLT2i/RASi. Seven patients (6.67%) experienced an eGFR decline exceeding 30%, but a decline >10% was very common, occurring in 61.9% of patients (see Supplementary Table 2). Similarly, no significant differences were found among groups stratified by baseline eGFR levels or different SGLT2i/RASi combination regimens; however, eGFR decline >30% was more frequently observed in combination therapy groups and among patients in CKD G2/G3 stages. Hyperkalemia (serum potassium >5.5 mmol/L) occurred in 9 patients (8.57%), but only in those with baseline eGFR <60 mL/min/1.73m². No hyperkalemia was reported in the finerenone + SGLT2i group, whereas its incidence reached 37.5% in patients with eGFR <30 mL/min/1.73m², among whom 3 required dose adjustment or drug discontinuation.

Table 1:​​ Overall changes in UACR and 24H-UP during the 12-week follow-up period.

Table 2:​​ Risk of hyperkalemia and eGFR decline among patients in different treatment groups and different eGFR subgroups during follow-up.

Within the first 12 weeks of initiating finerenone add-on therapy for T2D-related CKD, finerenone demonstrated clear efficacy in reducing proteinuria, regardless of concomitant RASi/SGLT2i use. The commonly observed mild early eGFR decline is considered the pharmacological basis for long-term cardiorenal benefits and does not necessitate drug discontinuation. Hyperkalemia can be effectively managed with standard treatments, and severe hyperkalemia was uncommon. However, closer monitoring of eGFR and serum potassium levels is mandatory for patients with advanced CKD and significantly reduced baseline eGFR.