Recharging the Powerhouse: Mitochondrial Dysfunction and Therapy in Cardiorenal Syndrome Type 4.

PURPOSE OF REVIEW

Cardiorenal syndrome type 4 (CRS-4) is characterised by the development of cardiac dysfunction secondary to chronic kidney disease (CKD). This review outlines the pathophysiology of CRS-4, with a focus on the emerging role of mitochondrial dysfunction, and evaluates novel mitochondria-targeting therapeutics for CRS-4.

RECENT FINDINGS

Current research has positioned mitochondrial dysfunction in cardiomyocytes as a key driver of CRS-4 pathophysiology, characterised by impaired adenosine triphosphate production, increased reactive oxygen species (ROS) generation, dysregulated mitophagy, altered mitochondrial biogenesis and dynamics, and bioenergetic malfunction. Currently licensed drugs, such as dapagliflozin and sacubitril/valsartan, have demonstrated mitoprotective effects in CRS-4, and numerous other therapies targeting mitochondria have proven efficacious in preclinical studies. However, real-world clinical trials are required to determine whether mitochondria represent a viable therapeutic target that offers meaningful clinical benefits to patients with CKD. There is increasing evidence that mitochondrial dysfunction is a key pathomechanism in the development of CRS-4. Mitochondrial-targeting therapies offer a novel mechanism-driven approach, with numerous showing preclinical promise. However, real-world clinical trials are required to determine their therapeutic potential.