Kinetics of extracellular vesicles in hemodialysis

Hemodialysis (HD) is a lifesaving treatment for patients with end-stage kidney
disease (ESKD). Yet, apart from beneficial effects, HD has adverse
consequences, which, apart from rapid osmolarity and electrolyte shifts,
results from the bio-incompatibility (BI) of the extra-corporeal circuit (ECC)
and intradialytic hypotension (IDH). While BI arises within the EEC due to the
contact between circulating blood cells and the foreign materials of the ECC,
IDH-induced tissue injury (TI) originates within the body of the patients.
Activated cells can be detected by upregulation of cell surface markers and
release of degradation products. Substances which are smaller than the pores of
dialyzer-membranes may pass this barrier and, thus, become undetectable in
blood.
Various cell types shed small particles upon activation an/or injury, so called
extracellular vesicles (EVs). These EVs contain various proteins and are too
large to travers dialyzer membranes. Their assessment requires strict
pre-analytical precautions. In previous HD research, both pre-analytical
circumstances and analytic methods were insufficiently standardized, precluding
solid conclusions. Both BI and recurrent IDH, predispose to micro-inflammation
and cell activation, which are related to morbidity and mortality. Hence, when
analysed properly, the measuring of EVs might be a valuable tool to assess
dialysis-induced adverse side-effects, not only in the dialyser but also in the
body, which, when occurring repeatedly, may influence survival. Industrial
companies may use this information when designing and developing new machines
and devices for the benefit of our patients

To assess the kinetics of EVs in standard HD, derived from both in- (BI) and
outside (TI) the ECC.

Prospective observational (pilot) study

All measurements of this study are non-invasive and associated with negligible
risks. The burden is caused by extra blood pressure measurements and
non-invasive blood draws. Blood samples are collected during a regular dialysis
treatment (no extra visits) from the extracorporeal circuit (no
,venipunctures). The estimated blood volume (81.3 ml) is not expected to cause
a clinically relevant decrease in hemoglobin levels (estimated decrease in Hb
level: 0.2 mmol/L). In addition, as a precaution, patients with an Hb level <
6.2 are excluded. This cut-off value is based on the guidelines (target Hb in
hemodialysis patients: 6.2-7.4 mmol/l). Furthermore, the hemoglobin level will
be checked at the next treatment and, if necessary, the EPO dose will be
adjusted.