Sevelamer use, vitamin K levels, vascular calcifications and vertebral fractures in hemodialysis patients: results from the VIKI study

Hyperphosphatemia is a risk factor for vascular calcifications (VCs), which are part of the chronic kidney disease-mineral and bone disorders (CKD-MBD). Vitamin K-dependent proteins such as Matrix Gla Protein (MGP) and Bone Gla Proteins (BGP or osteocalcin) can inhibit VCs and regulate bone mineralization. In this analysis of the VIKI study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with/without sevelamer was evaluated. Levels of vitamin K vitamers: K1 and K2 or menaquinones (MK; MK4-7), total and undercarboxylated (uc) forms for both BGP and MGP were determined. While no differences in clinical characteristics were noted, lower levels of MK4 (0.45 vs. 0.6 ng/mL, p=0.01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% vs. 5.4%, p=0.005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (OR: 2.64, 95% CI: 1.25-5.58, p=0.011) and aortic calcification (OR: 8.04, 95% CI: 1.07-60.26, p=0.04). In the same logistic model, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP<150 μg/L compared to those with total BGP ≥150 μg/L (OR: 3.15, 95% CI: 1.46-6.76, p=0.003). In contrast, there was no such effect in those untreated (total BGP<150 μg/L vs. total BGP≥150 μg/L: OR: 1.21, 95% CI: 0.66-2.23, p=0.54] (p=0.049 for effect modification by sevelamer). Sevelamer may interfere with MK4 levels in HD patients and interact with low BGP levels to increase bone fractures in CKD patients.