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Sevelamer Use, Vitamin K Levels, Vascular Calcifications, and Vertebral Fractures in Hemodialysis Patients: Results from the VIKI Study
Author(s) -
Fusaro Maria,
Cozzolino Mario,
Plebani Mario,
Iervasi Giorgio,
Ketteler Markus,
Gallieni Maurizio,
Aghi Andrea,
Locatelli Francesco,
Cunningham John,
Salam Syazrah,
Zaninotto Martina,
Ravera Maura,
Russo Domenico,
Mereu Maria Cristina,
Giannini Sandro,
Brandi Maria Luisa,
Ferrari Serge,
Sella Stefania,
Egan Colin Gerard,
Bellasi Antonio,
Di Lullo Luca,
Tripepi Giovanni,
Nickolas Thomas
Publication year - 2021
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4214
Subject(s) - matrix gla protein , vitamin k2 , medicine , odds ratio , hyperphosphatemia , sevelamer , osteocalcin , endocrinology , vitamin d and neurology , gastroenterology , calcification , logistic regression , urology , kidney disease , vitamin , chemistry , alkaline phosphatase , biochemistry , enzyme
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 Vitamin K Italian (VIKI) study, the relationship between vitamin K status, vertebral fractures (VFs) and VCs in 387 hemodialysis (HD) patients with ( N = 163; 42.1%) or without N = 224; 57.9%) 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. Although no differences in clinical characteristics were noted, lower levels of MK4 (0.45 versus 0.6 ng/mL, p = .01) and a greater MK4 deficiency was observed in sevelamer‐treated patients (13.5% versus 5.4%, p = .005). Multivariate logistic regression revealed that MK4 deficiency was associated with sevelamer use (odds ratio [OR] = 2.64, 95% confidence interval [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, sevelamer amplified the effect of total BGP levels on the odds of VFs in patients with total BGP <150 μg/L compared with those with total BGP ≥150 μg/L (OR = 3.15, 95% CI 1.46–6.76, p = .003). In contrast, there was no such effect in those untreated (total BGP <150 μg/L versus total BGP ≥150 μg/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. © 2020 American Society for Bone and Mineral Research (ASBMR).