Clinical trial NCT05957146: Kinetics of Extracellular Vesicles in Hemodialysis
Official title: Kinetics of Extracellular Vesicles in Hemodialysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: End-stage Kidney Disease
Keywords: Hemodialysis
Extracellular vesicles
Bio-incompatibility
Tissue injury
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Dianet Dialysis Centers
First posted: 2023-07-24
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults patients treated with chronic intermittent hemodialysis (3x per week during 4 hours) during at least 3 months

Brief summary: The aim of this observational study is to gain insight into the kinetics of extracellular vesicles (EVs), derived from both in- (i.e. bio-incompatibility) and outside (tissue-injury) the extracorporeal circuit (ECC), during standard hemodialysis (HD) in adult prevalent end-stage kidney disease (ESKD) patients treated with HD.

During a single HD session, blood samples for EV-assessment will be taken at several time points and at different sampling sites in the extracorporeal circuit (sampling point 1: before the rollerpump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).

Detailed description: Hemodialysis (HD) is a lifesaving treatment for ESKD patients. Yet, apart from beneficial effects, HD has adverse consequences, which, apart from rapid osmolality and electrolyte shifts, results from the bio-incompatibility (BI) of the extra-corporeal circuit (ECC) and intradialytic hypotension (IDH) as well. While BI arises within the ECC due to the contact between circulating blood cells and the foreign materials of the lines and dialyzer, 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, which are shed by various cell types upon activation and/or injury, contain various proteins and are too large to travers dialyzer membranes. Their assessment requires strict and standardized collection and handling of blood samples. In previous HD research, both pre-analytical circumstances and analytic methods were insufficiently standardized, precluding solid conclusions. Both the contact between circulating blood cells and the ECC, 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 dialyzer but also in the body, which, when occurring repeatedly, may influence survival.

In a recent study, we found an increase in EVs during treatment with different dialysis modalities. However, EVs were only assessed before and after dialysis. Hence, in the present study, we aim to assess the kinetics of EVs in routine HD.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years
* Stable clinical situation: free of infection, no recent admission
* HD \>3 months
* Haemoglobin level \>6,2 mmol/L
* Residual diuresis \<200mL/24h
* Willing and able to give written informed consent.

Exclusion Criteria:

* Active infection, malignancy, auto-immune disease, or treatment with immunosuppressive medication.
* Allergy to polysulfone dialysers
* Life expectancy \<3 months due to non-renal disease
* Access recirculation

Primary outcomes:
measure: Intradialytic change in the concentration of extracellular vesicles from specific cell types
timeFrame: 4 hours (=one dialysis treatment); assessed at the following time points: 0 minutes (start of dialysis), 30 min, 60 min, 120 min, 180 min, 235 minutes
Secondary outcomes:
measure: Intradialytic blood pressure
timeFrame: 4 hours (=one dialysis treatment); measured 4x/hour
measure: Hematocrit (Ht)
timeFrame: 4 hours (=one dialysis treatment); measured three times (at the start (0 minutes), half way (120 minutes) and at the end (240 minutes))
measure: High sensitive CRP (hsCRP)
timeFrame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
measure: White blood cell (WBC) count
timeFrame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
measure: Platelet count
timeFrame: 4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Dianet Amsterdam
state: Noord-Holland
Study officials:
affiliation: VUmc
name: Muriel PC Grooteman, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: