Activation of the Contact System and the Immune System in Patients With Chronic Kidney Disease. (AKIM-CKD)

Activation of the Contact System and the Immune System in Patients With Chronic Kidney

Patients with end-stage renal disease undergoing hemodialysis (HD) are burdened with extremely high mortality rates (15% per year) and during the early stage (≤120days) the mortality rate is even higher (27% per year). Cardiovascular complications and bloodstream infections (BSIs) account for the vast majority of deaths in HD patients. In Denmark, BSIs occur in 14% of HD patients per year and is most frequently caused by Staphylococcus aureus (44%). The most frequent infectious complication is endocarditis that has fatal outcomes in ≈50% of the cases. Overall, 10% of HD patients die within 30 days after a positive blood culture for S. aureus. This project aims to answer key questions regarding HD patients' decreased ability to fight S. aureus BSIs and in particular the potential exacerbating effect of HD. We hypothesize that HD patients' blood is significantly compromised by the process of HD, to an extend that lowers immunoactivity against S. aureus. Moreover, we hypothesize, that contact activation promotes the coagulability of blood thus promoting biofilm formation by S. aureus which increases the overall risk of BSI. We will test these hypotheses by collecting blood and analyzing the inflammation and coagulation status in plasma samples from participants before and after HD. We will compare the level of the inflammatory markers in plasma from participants undergoing HD (n=180) to the level in plasma samples from three control groups: healthy volunteers (n=120), participants with renal disease not in dialysis (n=60) and participants undergoing peritoneal dialysis (n=40).

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease Requiring Chronic Dialysis
• Intervention / Treatment: Other: Observational study

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Katrine Pilely, PhD; Phone Number: 0045 20963328; Email: kapi@sdu.dk

Study Locations

• Denmark
  • Odense, Denmark, 5230
    • Recruiting
    • Odense University Hospital
    • Contact: Katrine Pilely

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Blood samples and clinical information is collected from 180 participants with chronic kidney disease undergoing hemodialysis, before and after dialysis. Their levels of components from the innate immune system in plasma are compared to the levels in plasma samples from three control groups: 60 participants with chronic kidney disease not in dialysis, 60 participants with chronic kidney disease undergoing peritoneal dialysis and 120 healthy volunteers.

Description

Participants with chronic kidney disease undergoing hemodialysis Inclusion criteria

• Age >18 years
• Chronic kidney disease
• Hemodialysis

Exclusion criteria:

- Acute kidney disease

Participants with chronic kidney disease, not in dialysis Inclusion criteria

• Age >18 years
• Chronic kidney disease (eGFR from <15 to 44)

Exclusion criteria:

• Acute kidney disease
• Hemodialysis
• Peritoneal dialysis

Participants with chronic kidney disease undergoing peritoneal dialysis Inclusion criteria

• Age >18 years
• Chronic kidney disease
• Peritoneal dialysis

Exclusion criteria:

- Acute kidney disease

Healthy volunteers Inclusion criteria

• Age >18 years
• Blooddonors

Exclusion criteria:

- NA

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy participants	Other: Observational study; Observational study
Participants with chronic kidney disease undergoing hemodialysis	Other: Observational study; Observational study
Participants with chronic kidney disease, not in dialysis	Other: Observational study; Observational study
Participants with chronic kidney disease undergoing peritoneal dialysis	Other: Observational study; Observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma level of cHK	cHK is the final activation product of the contact activation system	At enrollment

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: University of Southern Denmark

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2032

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Infection; End-stage renal disease; Chronic kidney disease; Hemodialysis; Coagulation; Contact system; Innate immune system
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: OP_1579

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