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 bonedisorders (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 Vitamin K Italian (VIKI) study, the relationship between vitaminK status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with (N= 163; 42.1%) or withoutN= 224; 57.9%) seve-lamer was evaluated. Levels of vitamin K vitamers K1 and K2 or menaquinones (MK; MK4–7), total and undercarboxylated (uc) formsfor both BGP and MGP were determined. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 ver-sus 0.6 ng/mL,p= .01) and a greater MK4 deficiency was observed in sevelamer-treated patients (13.5% versus 5.4%,p= .005). Mul-tivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidenceinterval [CI] 1.25–5.58,p= .011) and aortic calcification (OR = 8.04, 95% CI 1.07–60.26,p= .04). In the same logistic model, sevelameramplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150μg/L compared with those with total BGP≥150μg/L (OR = 3.15, 95% CI 1.46–6.76,p= .003). In contrast, there was no such effect in those untreated (total BGP <150μg/L versustotal BGP≥150μg/L: OR = 1.21, 95% CI 0.66–2.23,p= .54];p= .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.