Kinetics of Extracellular Vesicles in Hemodialysis

End-stage Kidney Disease Clinical Trial

Official title:

Kinetics of Extracellular Vesicles in Hemodialysis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05957146
• Other study ID #: NL84115.018.23
• Status: Not yet recruiting
• Start date: August 2023
• Est. completion date: August 2024

Study information

• Verified date: July 2023
• Source: Amsterdam UMC, location VUmc
• Contact: Muriel PC Grooteman, MD PhD
• Phone: +3120 566 5990
• Email: mpc.grooteman[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End-stage Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Amsterdam UMC, location AMC, Dianet Dialysis Centers

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intradialytic blood pressure	Change in systolic and diastolic blood pressure (mmHg) during dialysis	4 hours (=one dialysis treatment); measured 4x/hour
Secondary	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))
Secondary	High sensitive CRP (hsCRP)	Marker of inflammation	4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)
Secondary	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)
Secondary	Platelet count	Number of platelets in blood	4 hours (=one dialysis treatment); measured once at the start of dialysis (0 minutes)