#3325 EXTRARENAL CYP27B1 ACTIVITY CONTRIBUTES TO THE CIRCULATING POOL OF 1,25(OH)2D

Abstract Background and Aims Alterations of vitamin D metabolism are ubiquitous in patients with chronic kidney disease (CKD) a key feature the syndrome CKD-mineral bone disorder. A central paradigm is that kidneys only relevant source activation for systemic effects. However, various cells tissues exhibit CYP27B1 activity capable producing 1.25(OH)2D, which could contribute to circulating pool [1]. This longitudinal, observational study challenges dogma as by investigating metabolites anephric free active therapy. Method Anephric therapy were included at time transplantation. subset had second visit 12 months post-transplant. Liquid chromatography–tandem mass spectrometry was used measure 25(OH)D2/3, 1,25(OH)2D3 24,25(OH)2D3. Metabolic ratios over precursors measures CYP24A1 (24,25(OH) 2D3/ 25(OH)D3) CYP27B1(1,25(OH)2D/ activity. Biointact PTH (1-84) measured an in-house immunoradiometric assay [2] FGF23 ELISA (Kainos Laboratories, Tokyo, Japan). Interleukin 6 (IL6), tumor necrosis factor-Α (TNF- Α) interferon-Γ (IFN-Γ) using electrochemiluminescence multiplex immunoassay (Human Proinflammatory 1 V-plex, MSD, Maryland, US). Two independent laboratories performed confirmatory analyses 1,25(OH)2D. Results All (n = 38) detectable (>2.5 pg/mL) levels 1,25(OH)2D, median value 13.5 pg/mL (range 3.9 35.7 pg/ml). There significant correlation between 25(OH)D 1,25(OH)2D (r 0.583, p≪0.001), 25(OH)D-levels explaining 34% variation (Fig. 1). not significantly correlated (rho 0.279, p 0.09) or –0.280, 0.09), nor any inflammatory markers; IL6 0.068, 0.69), TNF-Α –0.264, 0.11), IFN-Γ –0.001, 0.99). To validate our findings, anonymized samples 17 CKD stage 5D residual renal function sent two laboratories. The presence confirmed all patients. Twenty-five underwent successful transplantation After transplantation, 25(OH)D-level decreased, while 1,25(OH)₂D 24,25(OH) ₂D substantially increased. metabolic expressing both increased 2). At post-transplant, 1,25(OH)₂D-levels biointact 0.603, 0.002), but –0.262, 0.21). Conclusion Extrarenal contributes may sustain low-normal D, even individuals. While hormonally regulated, extrarenal seems be mainly substrate dependent.