Therefore, it is hypothesized that at clinically relevant plasma concentrations, BUP or its metabolites, modulated Oct2, Oatp4c1 and Mate1 mediated renal transport of ADMA and/or Ddah1 mediated metabolism, which could alleviate the exacerbation of ADMA and retard the progression of renal interstitial lesions and fibrosis. This evidence concerns the gene SLCO4C1 and fibrosis.