Influence of vitamin K status on bone metabolism and vascular calcifications in children with renal failure on dialysis

Vitamin K is besides a co-factor in coagulation proteins also a necessary
co-factor for osteocalcin and matrix Gla protein (MGP). These vitamin K
dependent proteins play an important role in regulation of bone formation and
inhibition of vascular calcifications respectively. Renal bone disease and
cardiovascular disease are both significant problems for patients with chronic
kidney disease. Current dietary requirements of vitamin K are based on the
maintenance of normal concentrations of prothrombin, not of osteocalcin and
MGP.
Osteocalcin, also named bone Gla protein (BGP), is a 49 amino-acid protein with
3 gamma-carboxyglutamate (Gla) residues. Vitamin K is a necessary co-factor to
effectively carboxylate osteocalcin. Increase of vitamin K intake results in
markedly higher carboxylation rate of osteocalcin. Beneficial effects of
vitamin K on prevention of bone fractures in adults were found in several
studies. In healthy children subclinical vitamin K deficiency has recently been
described and a better vitamin K status was found to be associated with an
increased bone mineral content . In adult patients on haemodialysis suboptimal
vitamin K status has been found as well. MGP is a 84 amino acid Gla protein,
containing 5 Gla residues. It is found in bone and cartilage, but is also
expressed by chondrocytes and vascular smooth muscle cells . Arterial
calcification results from the imbalance between factors favouring calcium
deposition and inhibitory factors of deposition of calcium. Several studies
indicate MGP plays a major role in the inhibition of vascular calcification.

To determine the vitamin K status in children with chronic renal failure
(peritoneal dialysis patients, hemodialysis patients) and evaluate whether a
correlation between bone and vascular parameters and vitamin K status exists.
If vitamin K status is suboptimal, in a later stage oral vitamin K
supplementation can be given to improve vitamin K status.

Children on dialysis will be recruited from paediatric nephrology departments
in two University hospitals in the Netherlands (Nijmegen and Utrecht). These
patients are seen frequently at the out-patient clinic. For follow-up regular
visits will be used. In total 20-30 patients will be recruited.
At baseline blood sampling will be performed from all patients (during regular
vena puncture) for analysis of vitamin K status blood parameters of bone
metabolism, radiologic parameters of bone metabolism and blood parameters of
increased cardiovascular risk.
Patients on peritoneal dialysis will be asked to bring a sample of used
dialysis fluid.
during 1 week patients will be asked to keep a diary of their dietary intake

no extra risks
Possible benefit: extreme vitamin K deficiency (<3SD of normal value) that
might be detected will be treated