Finerenone Added to Renin-Angiotensin System- and Sodium-Glucose Cotransporter 2 Inhibition in Patients with Alport...

Alport syndrome is a common hereditary glomerular kidney disease characterized by a high risk of kidney failure. Despite renin-angiotensin system- (RASi) and SGLT2 inhibitors (SGLT2i), a subset of patients experience rapid decline in kidney function. Preclinical data in Alport mice suggest that the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone could provide additional nephroprotection. This case series evaluates the changes in albuminuria and the safety of finerenone as part of a triple-therapy regimen in individuals with Alport syndrome.

In this retrospective, two-center observational case series, ten male individuals with Alport syndrome received finerenone (10 mg/day) in addition to baseline-therapy with RASi (100%) and SGLT2i (90%). Clinical parameters - including estimated glomerular filtration rate (eGFR), albuminuria, and serum potassium were analyzed over a mean follow-up period of 9 ± 5 months.

Median albuminuria showed a non-significant decrease of 33% during follow-up, from 3506 [IQR 1645-4304] to 2346 [1858-2792] mg/g creatinine (p = 0.21). Median eGFR declined from 50 [47-112] to 43 [32-116] mL/min/1.73m2 (p = 0.03) and continued to decline in a subgroup of five individuals, who were followed for 12 months. Hyperkalemia occurred in half of the individuals, necessitating the use of potassium binders in two cases. Finerenone was discontinued in two individuals due to rapid decline of eGFR. No serious adverse events were observed.

This real-world case series provides preliminary evidence that adding finerenone to baseline therapy with RASi and SGLT2i is feasible and may offer additional albuminuria reduction in Alport syndrome. However, the notable eGFR decline and the relevant incidence of hyperkalemia underscore the necessity for vigilant clinical monitoring. While multimodal nephroprotection remains a promising tool to delay disease progression, these real-world observations provide pilot data to inform the design of future large-scale prospective trials in patients with Alport syndrome.