Kinetics of Extracellular Vesicles in Hemodialysis

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).

Study Overview

• Status: Completed
• Conditions: End-stage Kidney Disease
• Intervention / Treatment: Device: Routine hemodialysis

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.

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Dianet Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Chronic hemodialysis patients; Adult patients treated with routine hemodialysis 3x/week during at least 3 months

Device: Routine hemodialysis; Dialyzers: Cordiax FX80 dialyzers; membrane material HelixonePlus (polysulfone); (Fresenius Medical Care Bad Homburg, Germany); Dialysis machines: Baxter Gambro AK 98 (Gambro Lundia AB, Lund, Sweden; part of Baxter Healthcare Corporation); Needles for vascular access: Nipro SafeTouch dialysis cath 1.6x25 mm (16G) or 1.9x25 mm (15G); or Nipro SafeTouch Tulip needles (15G; all Nipro Medical Europe Mechelen, Belgium); Ultrapure dialysis fluids (less than 0.1 colony forming units/ml, less than 0.03 endotoxin units/ml) will be mixed with AC-F 219/1 or 213/4 liquid acid concentrates and BiBag dry bicarbonate concentrate. Hence, the electrolyte composition of the dialysis fluid will be: Na 138-142 mmol/L; K 2.0-3.0 mmol/L; HCO3 26-35 mmol/L; Ca 1.25-1.50 mmol/L; Mg 0.5 mmol/L; Cl 108.5-109 mmol/L; glucose 5.6 mmol/L; acetate 3 mmol/L. Dialysate flow rate will be 500 mL/min.; Anticoagulation: nadroparin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intradialytic change in the concentration of extracellular vesicles from specific cell types	Blood cell-derived EVs: platelets: CD61+, activated platelets: CD61+/CD62p+; erythrocytes: CD235a+; leukocytes CD45+; and endothelium-derived EVs: CD144+, activated endothelium CD62e+; myocardium and endothelium-derived: Connexin-43+ will be measured at different sampling sites (sampling point 1: before the roller pump, arterial line; sampling point 2: after the rollerpump and before the dialyzer, sampling point 3: after the dialyzer, efferent line).	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intradialytic blood pressure	Change in systolic and diastolic blood pressure (mmHg) during dialysis	4 hours (=one dialysis treatment); measured 4x/hour
Hematocrit (Ht)	the volume percentage of red blood cells (RBCs) in blood	4 hours (=one dialysis treatment); measured three times (at the start (0 minutes), half way (120 minutes) and at the end (240 minutes))
High sensitive CRP (hsCRP)	Marker of inflammation	4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
White blood cell (WBC) count	Total white blood cell count and differential count	4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Platelet count	Number of platelets in blood	4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Dianet Dialysis Centers
• Investigators: Principal Investigator: Muriel PC Grooteman, MD PhD, VUMC

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2023
• Primary Completion (Actual): February 9, 2024
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: July 4, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Hemodialysis; Extracellular vesicles; Bio-incompatibility; Tissue injury
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: NL84115.018.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No