1. Introduction Conclusions Liver transplant recipients with impaired renal function or a low dose-adjusted tacrolimus concentration suggesting a high CYP3A4 activity are at risk of low 1,25(OH) 2 D 3 and might require treatment with activated vitamin D analogues The use of tacrolimus does not lead to an increase in 1,25(OH) 2 D 3 in a clinical setting. 1.To identify factors associated with 1,25(OH) 2 D 3 concentrations in LT recipients with emphasis on the renal function and catabolism 2.To test the hypothesis that tacrolimus leads to an increase in 1,25(OH) 2 D 3 concentrations in LT recipients, a cohort of patients with a primary non- renal disease in whom an up regulation of the renal 1- α –hydroxylase is not likely to play a pivotal role FACTORS REGULATING 1,25-DIHYDROXYVITAMIN D 3 CONCENTRATIONS IN LIVER TRANSPLANT RECIPIENTS A Prytuła (1) J Vande Walle (1) H Van Vlierberghe (2) JM Kaufman (3) T Fiers (4) J Dehoorne (1) A Raes (1) Department of (1) Pediatric Nephrology and Rheumatology (2) Gastroenterology and Hepatology, (3) Endocrinology and (4) Clinical Chemistry at the Ghent University Hospital, Belgium Following liver transplantation (LT), the 25(OH)D 3 and vitamin D binding protein (VDBP) concentrations rise, but no significant increase in 1,25(OH) 2 D 3 has been reported (1). Factors potentially contributing to the discrepant 25(OH)D 3 and 1,25(OH) 2 D 3 concentrations are impaired 1,25(OH) 2 D 3 synthesis due to a deterioration in renal function or enhanced catabolism. 24-hydroxylase is the main enzyme catabolizing 1,25(OH) 2 D 3 in the kidney, but there is also evidence that the drug metabolizing enzyme CYP3A4 catalyses the 1,25(OH) 2 D 3 degradation in the intestine and liver (2). Rodent studies demonstrated that calcineurin inhibitors (CNI) increase the synthesis of 1,25(OH) 2 D 3 (3). A significant increase in 1,25(OH) 2 D 3 due to an improvement of the renal function and up regulation of the renal 1- α –hydroxylase has been documented in renal allograft recipients. We hypothesized that this may also be due to the CNI use. Objectives Patients and Methods Results Design: prospective longitudinal observational study Patients: 41 LT recipients on tacrolimus; transplantation between July 2011 and Dec 2013 Procedures: -serum 25(OH) D 3, 1,25(OH) 2 D 3 and 24,25(OH) 2 D 3 measured before, at 2 weeks and 3 months after LT using liquid chromatography- tandem mass spectroscopy -dose-adjusted tacrolimus concentration (tacrolimus pre- dose concentration / daily tacrolimus dose) used as a surrogate marker of CYP3A4 activity -factors associated with 1,25(OH) 2 D 3 identified using multivariate linear regression analysis Factors associated with 1,25(OH) 2 D 3 at 3 months post LT: -estimated glomerular filtration rate (Fig. 1) -MELD score (pre LT) -dose-adjusted tacrolimus concentration (see Fig. 2) Fig. 2 all quartiles Kruskal-Wallis P< 0.001 quartile 1 and 4 Mann-WhitneyU P< 0.001 Fig. 1 all quartiles Kruskal-Wallis P= 0.053(NS) quartile 1 and 4 Mann-WhitneyU P= 0.02 vitamin D metabolites preLT (IQR) 2w (IQR) 3m (IQR) preLT- 2w preLT- 3m 25(OH)D 3 (ng/ml)18 (24)14 (11)26 (21)P= 0.07P= 0.03 1,25(OH) 2 D 3 (pg/ml)55 (62)37 (35)46 (34)P= 0.002P= 0.37 24,25(OH) 2 D 3 (ng/ml) 1.5 (1.1)-1.5 (0.6)N/AP= 0.17 Vitamin D metabolites concentrations at baseline, 2 weeks and 3 months post LT References 1.Reese PP et al. Changes in vitamin D binding protein and vitamin D concentrations associated with liver transplantation. Liver international 2012 2.Xu Y et al. Intestinal and hepatic CYP3A4 catalyze hydroxylation of 1alpha,25- dihydroxyvitamin D3: implications for drug-induced osteomalacia. Molecular pharmacology 2006 3.Lee CT et al. Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. American journal of nephrology 2011