Fig. 6

NAM function in CKD. NAM induces the activity of SIRT1 and promotes the deacetylation of SMAD3, p53, PGC-1α, and FOXO1. Deacetylation of SMAD3 inhibits fibrosis. Deacetylation of p53 inhibits apoptotic injury. Deacetylation of PGC-1α promotes its activation, which is associated with mitochondrial biogenesis and the production of the de novo pathway enzyme, quinolinate phosphoribosyl transferase (QPRT). Deacetylation of FOXO1 promotes its activation. The functions of FOXO1 in CKD are not fully explored. PGC-1α levels decrease in CKD. NAM-induced production of β-hydroxybutyrate and activation of HCAR2 may improve kidney function under conditions of PGC-1α deficiency, acting through unknown downstream mechanisms. SIRT1 may affect the activity of HIF-1α