Maria Fusaro 1, M.D., Ph.D., Marianna Noale 1, M.S.C., Giovanni Tripepi 2, M.S.C., Antonio Piccoli 3, M.D., Agostino Naso 4,M.D., Sandro Giannini 5, M.D., Davide Miozzo 3,M.D., Chiara Venturelli 6, M.D., Angelo Pica 6, M.D., Giuliano Brunori 6, M.D., Rosalba Cristofaro 3, M.D., Maurizio Gallieni 7, M.D for the VC (Vascular Calcification) Study Group 1 CNR-Institute of Neuroscience, Aging Section, Padua, Italy; 2 Istituto di Biometeorologia, Reggio Calabria, Italy; 3 Nephrology Unit, University of Padua, Italy; 4 Nephrology and Dialysis Unit, Hospital of Padua; 5Clinica Medica1°, University of Padua, Italy; 6Nephrology and Dialysis Unit, Ospedale di Trento, Italy; 7Nephrology and Dialysis Unit, Ospedale San Carlo Borromeo, Milan, Italy INTRODUCTION and AIMSMETHODS Sevelamer (S.), a calcium free phosphate binder, is also known for its ability to reduce serum cholesterol due to its binding affinity for bile acids. The aim of this study was to evaluate if the use of S. is associated with reduced serum levels of fat-soluble Vitamins (D and K) in patients with end stage renal disease (ESRD) In a cross-sectional study of 387 hemodialysis patients (42,1% on S. treatment) from 18 dialysis centers, we determined serum concentrations of: 25(OH)-vitamin D and several vitamers of the vitamin K complex (vitK1, and vitain K2 vitamers or menaquinones: MK4, MK5, MK6 and MK7) by high performance liquid chromatography (HPLC). In addition, routine biochemistry and vitamin K related proteins (osteocalcin, or Bone Gla Protein – BGP and Matrix Gla Protein – MGP) were also determinated. We confirm in humans (dialysis patients on long-term S. treatment), that S may interfere with vitamin K metabolism, based on an association with reduced MK4 levels and with different serum levels of vitamin K related proteins. These findings suggest that further studies are needed to confirm this association and determine if vitamin K2 supplementation is indicated in S. treated ESRD patients. REFERENCES: Patients treated with S. compared with not treated patients, we observed no significant differences in serum levels of 25(OH)-vitamin D and of most vitamin K vitamers: vitamin K1, MK5, MK6, MK7. However, more S. treated patients had MK4 deficiency (13,5% vs 5,4%, p=0,0052) (Fig 1). Further, in S. treated patients we found higher levels of alkaline phosphatase (median, 89 vs. 77,5 U/L, p=0,0002), total BGP (median, 210 vs. 152 mcg/L, p=0,0022) (Fig 2) and lower levels of total MGP (median 164, vs 20,3 nmol/L, p=0,0368) (Fig 3) RESULTS CONCLUSIONS SERUM LEVELS OF FAT-SOLUBLE VITAMIN D AND VITAMIN K IN SEVELAMER TREATED END STAGE RENAL DISEASE PATIENTS Fig 1. MK4 Deficiency in dialysis patients treated with Sevelamer Corresponding Author Maria Fusaro, M.D., Ph.D. CNR Aging Section, Institute of Neuroscience, Padua, Italy Via Giustiniani, 2, Padova, Italy. Telephone: FAX: Participating centers: Adria (Dott. Stoppa F; Dott.ssa Bernardi AM); Bassano del Grappa (Dott.ssa Pellanda V; Dott. Dell’Aquila R); Belluno (Dott. Tarroni G; Dott. De Paoli Vitali); Bolzano (Dott. Corradini R; Dott. Avolio M; Dott.Giacon B); Castelfranco V.to (Dott. Ferraro A; Dott. De Luca M); Dolo (Dott. Lucatello S; Dott.ssa Meneghel G); Feltre (Dott. Vianello A; Dott. Antonucci F); Firenze (Dott.ssa Grimaldi C; Dott. Mannarino A); Lodi (Dott. Barbisoni F; Dott. Elli A); Mestre (Dott. Morachiello P; Dott. Feriani M); Padova (Dott.ssa Rebeshini M; Dott. Naso A); Piove di Sacco-Chioggia (Dott.ssa Spinello M; Dott. Urso M); Rovigo (Dott.ssa Pati T; Dott. Gemelli A; Dott.ssa Bernardi AM); Schio (Dott.ssa Magonara FM; Dott. Axia M); Sesto SG (Dott. Ciurlino D; Dott. Bertoli S); Trento (Dott. Pica A; Dott.ssa Venturelli C; Dott. Brunori G); Treviso (Dott.ssa Puggia R; Dott.ssa Caberlotto A; Dott.ssa Mastrosimone S; Dott. Cascone C); Voghera (Dott.ssa Foschi A; Dott Milanesi F) Fig 2. Total BGP levels in patients traeted and not-treated with SevelamerFig 3. Total MGP levels in patients traeted and not-treated with Sevelamer