• Wenjun Lin, Xianfeng Wu, Jiejun Wen, Yang Fei, Junnan Wu, Xiaomei Li, Qunzi Zhang, Yang Dong, Tao Xu, Ying Fan, and Niansong Wang.
• Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: linwenjun5@126.com.
• Nutrition. 2021 Nov 1; 91-92: 111376.

ObjectivesAcute 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.MethodsWe 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-κB), and Klotho were determined by Western blot. Chromatin immunoprecipitation was used to assess the interaction of NF-κB, 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.ResultsThe 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-κB, 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.ConclusionsOur study demonstrated that Klotho preservation is essential for the renoprotection effect of nicotinamide, and provides a new preventive strategy for rhabdomyolysis-induced AKI.Copyright © 2021 Elsevier Inc. All rights reserved.

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