Short summary

Recent research has identified vitamin K deficiency as a potential contributor to the high risk of arterial and bone disease in kidney disease, but so far no blinded and placebo-controlled clinical studies have been completed to confirm or reject this hypothesis. The present study (RenaKvit) is a frontline research project that will increase our chances of knowing whether a daily supplement of vitamin K can counteract arterial and bone disease in dialysis ptt.

Rationale

Introduction

Vascular calcification is highly prevalent in patients with chronic kidney disease (CKD). The prevalence of aortic calcification is twice as high as the general population e.g. Cardiovascular disease (CVD) is the most frequent cause of death in patients with CKD. Compared to the background population, death due to CVD is 10-20 times higher in CKD patients being treated with hemodialysis. CKD patients in dialysis treatment also have a 3 times elevated risk of bone fractures compared to the general population, and low energy fractures are associated with a high mortality in CKD patients.

The excessive genesis of the vascular calcifications and osteopenia in CKD patients is still unresolved but seems to be multifactorial. The impaired kidney function in itself and the treatment, including dialysis, both seem of importance. More recently, it has been suggested that the vitamin K-dependent proteins named Matrix Gla Protein (MGP) and Osteocalcin (OC) may have important roles in vascular calcification and osteoporosis, respectively.

In recent years, it has become clear that CKD patients, in particular dialysis patients, are deficient in vitamin K. Accordingly, their vitamin K dependent protein profiles are abnormal and indicate an increased tendency to vascular calcification and bone de-calcification. It is therefore widely speculated whether vitamin K supplementation to CKD patients might improve their arterial and bone health. Biochemical data support this possibility, but randomized, double-blind and placebo controlled clinical trials testing the impact of vitamin K on harder clinical end points are still lacking.

Objectives and hypothesis

To examine the clinical effect of vitamin K2 (MK7) supplementation on arterial health as assessed from arterial stiffness (pulse wave velocity measurements) and radiographic imaging of coronary arteries and the abdominal aorta, as well as on bone health as assessed from measurement of bone mineral density by DXA-scans in patients on dialysis treatment.

RenaKvit is an investigator initiated, prospective, randomized, double-blind, placebo controlled intervention trial performed as a national multicenter trial that will run for 2 years. Patients are examined at baseline, after 1 and 2 years of intervention. Data is compiled after 1 and 2 years. All patients participate in examination of bone health, and a sub group of these in examination of arterial health.

Description of the cohort

Eligible participants are patients on dialysis treatmint with a dialysis vintage of more than 3 months, age ≥ 18 years, and a life expectancy of at least two years. Exclusion criteria (not elaborated here) are set to ensure lege artis methodology with respect to study design, study execution, and arterial calcification assessments. All participants provide their informed written consent.

Data and biological material

All participants:

Clinical data from patient files and patient interview

Biochemical samples (blood, urin)

Radiographic imaging (DXA scan, X-ray of lumbar column).

Arterial sub-group further:

Pulse-wave velocity

Heart CT

24 hour blood pressure

Collaborating researchers and departments

Steno Diabetes Center Copenhagen

• Marie Frimodt-Møller, MD, PhD

Department of Neurology, Herlev University Hospital, Copenhagen

• Ditte Hansen, MD, PhD

Department of Renal Medicine, Aarhus University Hospital

• Christian Daugaard Peters, MD, PhD
• Krista Dybtved Kjærgaard, MD, PhD
• Jens Dam Jensen, MD, PhD

Department of Nephrology, Aalborg University Hospital

• Charlotte Strandhave, MD, PhD

Department of Cardiology, Zealand University Hospital, Roskilde

• Hanne Elming, MD, PhD
• Carsten Toftager Larsen, MD, PhD

Department of Radiology, Zealand University Hospital, Roskilde

• Hanne Sandstrøm, MD

Department of Biochemistry and Immunology, Lillebaelt Hospital

• Claus Lohman Brasen, MD, PhD
• Anne Schmedes, MSc, PhD
• Jonna Skov Madsen, MD, PhD

Department of Clinical Biochemistry, Rigshospitalet

• Niklas Rye Jørgensen, MD, PhD, DMSc

Department of Radiology, Aalborg University Hospital

• Jens Brøndum Frøkjær, MD, PhD