NAD+ enhancers as therapeutic agents in the cardiorenal axis.

Cardiorenal diseases represent a complex interplay between heart failure and renal dysfunction, being clinically classified as cardiorenal syndromes (CRS). Recently, the contributions of altered nicotinamide adenine dinucleotide (NAD⁺) metabolism, through deficient NAD⁺ synthesis and/or elevated consumption, have proved to be decisive in the onset and progress of cardiorenal disease. NAD⁺ is a pivotal coenzyme in cellular metabolism, being significant in various signaling pathways, such as energy metabolism, DNA damage repair, gene expression, and stress response. Convincing evidence suggests that strategies designed to boost cellular NAD⁺ levels are a promising therapeutic option to address cardiovascular and renal disorders. Here, we review and discuss the implications of NAD⁺ metabolism in cardiorenal diseases, focusing on the propitious NAD⁺ boosting therapeutic strategies, based on the use of NAD⁺ precursors, poly(ADP-ribose) polymerase inhibitors, sirtuin activators, and other alternative approaches, such as CD38 blockade, nicotinamide phosphoribosyltransferase activation and combined interventions.