Nicotinamide retains Klotho expression and ameliorates rhabdomyolysis-induced acute kidney injury

Objectives: Acute kidney injury (AKI) is a severe complication of rhabdomyolysis that significantly increases mortality. Unfortunately, the therapeutic approach is limited. Inflammation plays a critical role in the pathogenesis of rhabdomyolysis-induced AKI, which is a potential therapeutic target. Nicotinamide, a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide, has been shown to have potent antiinflammation effects. Klotho is a tubular highly expressed renoprotective protein. Therefore, we explored the effect of nicotinamide on rhabdomyolysis-induced AKI and the underlying mechanisms. Methods: We intramuscularly injected glycerol to induce rhabdomyolysis, and intraperitoneally administrated nicotinamide to observe the effect on kidney injury. Interleukin-1 beta, tumor necrosis factor alpha, nuclear factor kappa B (NF-kappa B), and Klotho were determined by Western blot. Chromatin immunoprecipitation was used to assess the interaction of NF-kappa B, nuclear receptor corepressor, and histone deacetylase 1 with Klotho promoters. Small interfering RNA was used to evaluate the role of Klotho in nicotinamide-related renoprotection. Results: The results showed that nicotinamide attenuated renal pathologic morphology, kidney functional abnormalities, and kidney inflammatory response in rhabdomyolysis. Moreover, nicotinamide effectively blocked the recruitment of NF-kappa B, nuclear receptor corepressor, and histone deacetylase 1 to the promoter of Klotho, and preserved Klotho expression. More importantly, the renoprotection effect of nicotinamide was abrogated when Klotho was knocked down by small interfering RNA in rhabdomyolysis mice. Conclusions: Our study demonstrated that Klotho preservation is essential for the renoprotection effect of nicotinamide, and provides a new preventive strategy for rhabdomyolysis-induced AKI. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

This study demonstrated the renal protective effect of nicotinamide on rhabdomyolysis-induced AKI, with Klotho preservation being essential for this effect. The study provided insight into the interaction between nicotinamide and Klotho, and proposed a new preventive strategy for rhabdomyolysis-induced AKI.