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. Here, COMMD3 is linked to fibrosis.