Effects of Fhytomenadione on Coronary Artery Calcification of Hemodialysis Patients
Status:
Completed
Trial end date:
2020-01-02
Target enrollment:
Participant gender:
Summary
Until 2013 the reported incidence of chronic kidney disease varied widely between countries,
reporting the highest prevalence Taiwan, the region of Jalisco in Mexico and United States,
with 458, 421 and 363 individuals per million inhabitants respectively. Mexico has around
52,000 patients in replacement therapies, of which 80% of patients are treated in the
Instituto Mexicano del Seguro Social (IMSS).
In each stage of renal disease the principal cause of mortality is cardiovascular disease.
The risk of cardiovascular mortality is greater than the general population. Arterial
calcification, a marker of atherosclerosis and cardiovascular mortality predictor is common
in chronic kidney disease. The presence of arterial calcification leads to an increase in
arterial stiffness and to a decrease in coronary perfusion resulting in cardiac hypertrophy
and myocardial ischemia.
The presence of traditional cardiovascular risk factors like diabetes, hypertension,
hyperlipidemia and old age cannot fully explain the high prevalence of atherosclerosis and
arterial calcification in chronic kidney disease. Another specific factors related to chronic
kidney disease, like hyperphosphatemia, high calcium concentration in dialysis solutions, use
of high doses of vitamin D for the management of hyperparathyroidism has been shown to
positively influence development of arterial calcification. Invitro studies show that in
presence of hyperphosphatemia smooth muscle cells are transformed into osteoblast-like cells
that can express proteins that regulate mineralization. Two of this proteins, the matrix Gla
protein (MGP) and osteocalcin (OC) are regulators of tissue mineralization in arterial walls
and bones respectively. Vitamin K is required as cofactor in the gamma-carboxylation process
of several extracellular matrix proteins, converting inactive carboxylated proteins to
carboxylated active proteins. Prothrombin and coagulation factors 7,9 y 10 require vitamin K2
for its carboxylation process, while osteocalcin and the matrix Gal protein require vitamin
K1. Matrix Gla protein is a calcification inhibitor that plays an important role in the
prevention of arterial calcification. For carboxylation and correct function of the MGP is
necessary an enzymatic cofactor, vitamin K; this is corroborated in the fact that the
antagonism of vitamin K with warfarin antagonizes the carboxylation of MGP and produces rapid
arterial calcification.
There are currently no studies evaluating vitamin K in the prevention of vascular
calcification in patients with chronic kidney disease, therefore, the role of vitamin K in
the patient with kidney disease needs to be clarified with randomized controlled studies, in
which the target will be this population of patients at high risk. The aim of this study is
evaluate the effect of phytomenadione on coronary artery calcification of patients on
hemodialysis compared to placebo, our research hypothesis is that phytomenadione slows the
progression and favors the regression of coronary arterial calcification in patients on
hemodialysis compared to placebo, evaluating the coronary calcium score by coronary
tomography. As secondary objectives was determine changes in the baseline coronary calcium
score and at 12 months of use of phytomenadione and presence of cardiovascular events like
acute myocardial infarction, unstable angina and death of cardiac cause. The intervention
group received phytomenadione 10 mg (1 vial in the venous line of the extracorporeal
hemodialysis circuit) post hemodialysis 3 times a week for 12 months and the control group 1
vial of placebo solution (solution for injection in the venous line of the extracorporeal
hemodialysis circuit) post hemodialysis 3 times a week for 12 months. The follow-up of the
patients was for 12 months, at the end of the follow-up, a coronary control tomography was
performed by the Radiology Department to assess the final calcium score. Relative risk
measurement (RR), absolute risk reduction (ARR) and number to be treated (NTT) were
performed.
Phase:
N/A
Details
Lead Sponsor:
Instituto Mexicano del Seguro Social
Collaborators:
Marco Antonio Ocampo Apolonio Rodolfo Guardado Mendoza Texar Alfonso Pereyra Nobara