Because uremic toxins can alter the hepatic clearance of many drugs, either by downregulation of specific isoforms of CYP via affecting promoter40 or by impaired hepatic uptake mediated by uptake transporters,41 it is possible that the increased risk of RMP-induced hepatotoxicity in patients with end-stage renal disease was associated with the accumulation of uremic toxin. This evidence concerns the gene PPIG and stage 5 chronic kidney disease.