Influence of vitamin D treatment on functional expression of drug disposition pathways in human kidney proximal tubule cells during simulated uremia.

Effects of cholecalciferol (VitD) and calcitriol (1,25-VitD), on the expression and function of major vitamin D metabolizing enzymes (cytochrome P450 [CYP]2R1, CYP24A1) and select drug transport pathways (P-gp, /OATP4C1) were evaluated in human kidney proximal tubule epithelial cells (hPTECs) under normal and uraemic serum conditions.hPTECs were incubated with 10% normal or uraemic serum for 24 h followed by treatment with 2% ethanol vehicle, or 100 and 240 nM doses of VitD, or 1,25-VitD for 6 days. The effects of treatment on mRNA and protein expression and functional activity of select CYP enzymes and transporters were assessedUnder uraemic serum, treatment with 1,25-VitD resulted in increased mRNA but decreased protein expression of CYP2R1. Activity of CYP2R1 was not influenced by serum or VitD analogues. expression was increased with 1,25-VitD under normal as well as uraemic serum, although to a lesser extent. /P-gp mRNA expression increased under normal and uraemic serum, with exposure to 1,25-VitD. /OATP4C1 exhibited increased mRNA but decreased protein expression, under uraemic serum + 1,25-VitD. Functional assessments of transport showed no changes regardless of exposure to serum or 1,25-VitD.Key findings indicate that uraemic serum and VitD treatment led to differential effects on the functional expression of CYPs and transporters in hPTECs.