Nicotinamide riboside: A new promising therapy for type-I cardio-renal syndrome management

Introduction Epidemiological evidence correlates acute myocardial infarction (MI) with acute kidney injury (AKI), otherwise known as type-I cardio-renal syndrome (CRS). Multiple studies reported a decrease in tissue nicotinamide adenine dinucleotide (NAD) levels in myocardium in the setting of heart diseases and in the kidneys following AKI. The correlation between myocardial and renal NAD+ homeostasis in the context of type-I CRS, however, is yet to be determined as well as the opportunity to boost NAD synthesis in this pathological context. Objective We aim at evaluating the cardiac and renal protective effects of nicotinamide riboside (NR) supplementation, a precursor of NAD used by salvage enzymes renal NMRK1 and cardiac NMRK2, in a mouse model of large MI. Methods C57BL6/J male mice were divided into four groups: Sham + Vehicle, Sham + NR, MI + Vehicle, and MI + NR. NR was administered daily by intraperitoneal injection for either 4 or 7 days (D) post-MI. Echocardiography was performed and kidney structural, molecular, and functional levels were evaluated. Results Myocardial NAD levels were reduced at D4 and D7 post-MI when compared to the SHAM groups while they were maintained in MI + NR group. Renal NAD levels remained unchanged at D4 and D7 post-MI, whereas, NR treatment doubled NAD levels compared to the SHAM groups. Cardiac functional analysis revealed a comparable decrease in ejection fraction and cardiac output post-MI with or without NR treatment. Urine output decreased in mice at D4 and D7 post-MI but was maintained in NR treated mice. Kidney morphological alterations characterized by proximal tubule dilatation, fibrosis, and cell death markedly increased post-MI (D4 and D7), whereas NR treatment protected against these alterations. Conclusion NR supplementation appears as a promising therapy for type I CRS. Further experiments are warranted to decipher the molecular pathways involved in the observed protection.