Reversing Acute Kidney Injury through Coordinated Interplay of Anti-Inflammation and Iron Supplementation

Abstract

Acute kidney injury (AKI) induced by ischemia reperfusion is closely related to mitochondrial dysfunction. Nicotinamide adenine dinucleotide (NAD⁺ ) can enhance the mitochondrial function and restrain the following inflammation, but it is hardly delivered and lacks renal targeting ability. To address these problems, herein, an ultrasmall Fe₃ O₄ nanoparticle is used as a carrier to deliver nicotinamide mononucleotide (NMN), a precursor of NAD⁺ . An outstanding sophistication of the current design is that once NMN is attached on the surface of Fe₃ O₄ nanoparticles through its phosphate group, the remaining part is structurally highly similar to nicotinamide riboside, which provides an opportunity to deliver the NAD⁺ precursor into renal cells through nicotinamide riboside kinase 1 on the cell membrane. It is demonstrated that NMN-loaded Fe₃ O₄ nanoparticles can effectively reverse AKI induced by ischemia reperfusion. In-depth studies indicate that a well-timed iron replenishment following anti-inflammation treatment plays a determined role in recovering AKI, which distinguishes the current study from previous strategies centering on anti-ROS (reactive oxygen species), anti-inflammation, or even iron elimination.

Keywords: acute kidney injury; anti-inflammation; iron oxide nanoparticles; iron supplementation; red blood cells.