Nicotinamide Riboside: A Promising Treatment for Type 1 Cardiorenal Syndrome in Myocardial Infarction-Induced Acute Kidney Injury by Upregulating Nicotinamide Phosphoribosyltransferase-Mediated Nicotinamide Dinucleotide Levels.

BACKGROUND

Cardiorenal syndrome type 1 is characterized by the development of acute kidney injury following acute cardiac illness and notably acute myocardial infarction (MI). Acute kidney injury is considered an independent risk factor that increases mortality rate substantially. Nicotinamide adenine dinucleotide (NAD) is an important coenzyme in energy metabolism and oxidative phosphorylation, and in its oxidized form it is a substrate for multiple NAD+-dependent enzymes such as sirtuins and poly-ADP ribose polymerases. Decreased cardiac NAD levels, along with a downregulation of NAMPT (nicotinamide phosphoribosyl transferase), have been reported following MI. A compensatory upregulation in NMRK (nicotinamide riboside kinase) 2, an NAD+ biosynthetic enzyme that uses nicotinamide riboside (NR) to generate NAD+, takes place in the heart after MI, but the impact on kidney NAD metabolism and function has not been addressed before.

METHODS AND

RESULTS

MI was induced by ligating the left anterior descending coronary artery in 2-month-old C57BL6/J mice, followed by the administration of NR (IP injection, 400 mg/kg per day) for 4 and 7 days. We hypothesized that NR treatment could be a potentially promising therapy for MI-induced acute kidney injury. Our findings showed no significant improvement in cardiac ejection fraction following NR treatment at days 4 and 7 post-MI, whereas kidney functions were enhanced and morphological alterations and cell death decreased. The observed renal protection seems to be mediated by an upregulation of NAMPT-mediated increase in renal NAD levels, notably in the distal tubules.

CONCLUSIONS

Our findings indicate that NR could potentially be a promising therapy for acute kidney injury following an early stage of MI.