CALciPROTEIN crystallisation as Target in Endstage CKD: the T50 assay

Patients with Chronic Kidneys Disease (CKD) are at higher risk to developing
cardiovascular complications, specifically those in later stages. Approximately
50% of all deaths among CKD patients are caused by cardiovascular disease.
Calcification of the cardiovascular structures is a hallmark of CKD, and
related to this high risk. Currently, there is no tool to determine the
cardiovascular risk in this population in blood. The T50 is a novel in vitro
diagnostic bioassay which provides a functional read-out of the crystallization
of calcium phosphate in human blood, which drives the calcification process.
This T50 in turn correlates independently with the patient*s cardiovascular
risk. Importantly, the T50 of an individual is modifiable and can be improved
by for example adjusting medication, certain variables of dialysate
composition, or changing to another type of dialysis treatment. In this
proposed study the course of T50 during different dialyses types and other
known biomarkers in CKD patients will be evaluated. Additionally, the optimal
conditions of handling of the samples for clinical use will be determined.

In this study, two co-primary objectives are stated. The first one is to
analyse the change of T50 during haemodialysis treatments. The second primary
objective is to determine the effect of pre-analytical variables on the T50
measurements, specifically the storage of serum samples, and determine the
reference values. A secondary objective is to determine any association between
the T50 and other cardiovascular biomarkers, specifically markers for early
vascular damage and inflammation.

In this cross-sectional study, CKD stage 5 (CKD5) patients will be included who
are treated with daytime haemodialysis (n = 20) or nocturnal haemodialysis (n =
20) (CKD5D). Multiple blood samples will be collected during a haemodialysis
session from which T50 and other laboratory parameters will be determined.
Additional blood samples will be collected for the assessment of pre-analytical
variables. Serum will be aliquoted and stored at varying conditions after which
the T50 will be measured again. The same will be done for samples collected
from healthy individuals (n = 30). For the reference values only blood
collected from healthy individuals will be used. Finally, a selection of
cardiovascular biomarkers will be measured in all participants.

The CKD5D population in this study will already be treated with dialysis as a
part of their routine treatment. Drawing a volume of blood is the major burden
when participating in this study, even though this will not require
venepunctures in these patients. As for healthy participants, the blood
collection process can result in some pain due to the venepuncture. However,
the volume of blood is small and will therefore not result in a major burden.