FP348
VITAMIN D RECEPTOR ACTIVATION RAISES SOLUBLE THROMBOMODULIN IN CHRONIC KIDNEY DISEASE PATIENTS: A DOUBLE BLIND, RANDOMIZED, TRIAL

INTRODUCTION AND AIMS: Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix where it has a fundamental regulatory function for the endothelium-dependent response to inflammation and for the coagulation cascade. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates the synthesis of TM but the effect of this intervention on circulating TM has never been tested in CKD patients.

METHODS: We performed a post-hoc analysis of a 12-weeks double blind randomized trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow mediated vasodilatation (FMD) in the forearm (NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n=44; Placebo (PLA)=44] that took part into this trial.

RESULTS: Soluble TM at baseline was inversely with the GFR (ρ= -0.61, P<0.001) and FMD (ρ= -0.27, P=0.01). Alongside with the expected effects on bone mineral biomarkers, PCT produced a consistent rise (P=0.005) in TM levels, from a median value of 8446.0 pg/ml (IQR: 6227.8-10910.8 pg/ml) to 9127.5 pg/ml (6393.0-11287.3 pg/ml) while placebo had no effect (between-groups difference in median TM changes P=0.008). TM levels re-approached baseline values 2 weeks after stopping PCT. TM changes across the trial paralleled simultaneous changes in FMD.

CONCLUSIONS: In CKD patients VDR activation by PCT raises TM levels as well as the endothelium dependent response to ischemia and such effects are rapidly reversible after stopping the treatment. The TM rise induced by PCT is an additional mechanism whereby improvement in endothelial function by VDR activation may favorably impact upon vascular health in CKD patients.