What’s Missing In Diabetes Treatment? A Novel Agent Finerenone?

Diabetic Nephropathy and Finerenone

Abstract

Diabetic kidney disease represents a leading cause of chronic kidney disease and end-stage renal disease worldwide. The pathogenesis is primarily driven by persistent hyperglycemia, which induces oxidative stress, low-grade chronic inflammation, and activation of profibrotic signaling pathways. These mechanisms promote mesangial expansion, podocyte injury, and tubular epithelial-to-mesenchymal transition, culminating in glomerulosclerosis and tubulointerstitial fibrosis. Fibrosis is a hallmark of progressive diabetic kidney disease, characterized by excessive deposition of extracellular matrix components, leading to structural distortion and progressive decline in glomerular filtration rate.

Proteinuria, a key clinical manifestation of diabetic kidney disease, reflects dysfunction of the glomerular filtration barrier and serves as both a marker and mediator of disease progression. Filtered proteins exert direct cytotoxic effects on proximal tubular epithelial cells, inducing proinflammatory and profibrotic responses that exacerbate tubulointerstitial injury and accelerate fibrosis.
Despite standard-of-care therapy with renin-angiotensin-aldosterone system blockade, a significant proportion of patients exhibit residual proteinuria and progressive renal fibrosis, underscoring the need for additional therapeutic interventions. Mineralocorticoid receptor overactivation has emerged as a critical driver of renal inflammation and fibrosis in diabetic kidney disease. Finerenone, a novel non-steroidal, selective mineralocorticoid receptor antagonist, has demonstrated potent antifibrotic and antiproteinuric effects by attenuating the transcription of proinflammatory and profibrotic mediators, including transforming growth factor-beta and connective tissue growth factor. Finerenone reduces macrophage infiltration, extracellular matrix accumulation, and fibrosis in glomerular and tubulointerstitial compartments.

The landmark FIDELIO-DKD and FIGARO-DKD trials established the efficacy of finerenone in reducing albuminuria and slowing the progression of kidney disease in patients with type 2 diabetes and chronic kidney disease. By directly targeting key pathophysiological mechanisms of renal fibrosis and proteinuria, finerenone offers a novel and evidence-based therapeutic strategy to mitigate kidney disease progression in this high-risk population.