Acute kidney injury (AKI) is estimated to affect 3-10% of all hospitalized adults in the United States, making it one of the most common inpatient diagnoses. Despite this staggering incidence, most individuals exposed to AKI stressors, such as intravenous radiocontrast or cardiopulmonary bypass, do not develop AKI. In fact, whereas animal models of ischemia, sepsis, or nephrotoxicity suggest near-uniform responses to stressors, the natural history of stressed patients is highly heterogeneous. Recent studies of mitochondrial perturbations underlying experimental and human AKI suggest a conserved metabolic contribution to this variance. The renal tubule is only second to the heart in terms of mitochondrial abundance, reflecting the exquisite need for fuel combustion to generate the energy for active solute transport. The homeostasis of nicotinamide adenine dinucleotide (NAD+), a requisite coenzyme in oxidative metabolism, may be an important determinant of the renal response to AKI stressors. This mini-review highlights recent studies implicating NAD+ dysregulation in experimental and human AKI and summarizes findings from a pilot randomized trial to augment NAD+ among at-risk individuals.
Keywords: Tubule; Acute kidney injury; Acute renal failure; Mitochondria; Niacinamide; Nicotinamide; Nicotinamide adenine dinucleotide; Quinolinate; Vitamin B3.
© 2019 S. Karger AG, Basel.