Immune Function in Acute Kidney Injury

January 22, 2024 updated by: Guy's and St Thomas' NHS Foundation Trust

Evaluation of Immune Function in Patients With Acute Kidney Injury

The immune response to kidney damage during acute kidney injury (AKI) is an important contributor to the prolonged lack of renal function and progression of kidney injury. Most data related to intrarenal and interorgan pathways in AKI stem from animal research with sometimes conflicting results. Accurate evaluation of these processes in humans and identification of early diagnostic tools are critical for the development of strategies to prevent and attenuate AKI-related morbidity and mortality in patients.

The aim of this study is to evaluate immune function and miRNA expression in hospitalised patients with and without AKI.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Hypothesis:

An overriding pro-inflammatory immune response underlies AKI in humans which contributes to dysfunction of non-renal organs

Principal research question:

Is AKI in humans associated with a predominantly pro-inflammatory immune response?

Secondary research questions:

  1. Does AKI affect the phenotypic characterisation and function of neutrophils?
  2. Does severity of AKI lead to differences in phenotypic characterisation and function of neutrophils?
  3. What are the differences in cytokine profiles between AKI patients with and without systemic inflammation?
  4. What are the differences in cytokine profiles between AKI patients with systemic inflammation and patients with systemic inflammation without AKI?
  5. Is there a correlation between microRNA levels in patients with AKI and degree of AKI, renal recovery and patient outcome?

Study design:

Observational non-interventional study

Study population:

30 patients with AKI stage II or III * and systemic inflammation without sepsis 30 patients with AKI stage II or III * and no systemic inflammation 30 patients with systemic inflammation and normal renal function 30 patients after major surgery who do not have an infection, SIRS or AKI

* AKI will be defined by the KDIGO criteria

Primary outcome Detection of measurable phenotypic characteristics and function of leukocytes that are specific of patients with AKI.

Secondary outcomes:

  1. Differences in phenotypic characterisation and function of neutrophils between patients with AKI stage II and III.
  2. Differences in phenotypic characterisation and function of neutrophils between patients with and without AKI.
  3. Differences in cytokine profiles between patients with AKI and systemic inflammation and patients with AKI without systemic inflammation
  4. Differences in cytokine profiles between AKI patients with systemic inflammation and patients with systemic inflammation without AKI
  5. Correlation between microRNA levels in patients with AKI and renal recovery
  6. Correlation between microRNA levels in patients with AKI and patient outcome
  7. Differences in cytokine profiles between AKI patients without systemic inflammation and patients without AKI and without systemic inflammation / infection.

Statistical analysis:

For the analysis of laboratory variables that describe the immunological phenotype, standard statistical methods will be applied. 1) When the normal distribution assumption is met, groups will be compared using ANOVA and the corresponding contrasts for group by group comparisons; 2) In the absence of normality or for ordinal variables, Kruskal Wallis will be applied for multi-group comparisons, and Wilcoxon for two-groups analysis. We will apply multiple testing correction via Benjamini-Hochberg FDR control.

For the analysis of miRNA array data, we will first follow the protocol quality control measures appropriate for the platform of choice, and subsequently will carry out statistical analysis using the SAMr and LIMMA packages from Bioconductor, via the R software. Similarly, for the analysis of PCR data, the package HTqPCR from bioconductor will be used for quality control. Depending on the distribution of the final data, either non-parametric statistics, or a moderated t-test will be applied for statistical comparisons, with the corresponding multiple testing corrections as above.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SE1 7EH
        • Guy's & St Thomas Foundation Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Hospitalised patients

Description

Inclusion Criteria:

  • Adult patients (≥ 18 years) admitted to the hospital (incl ICU) with one of the following:

    1. postoperative AKI II or III and systemic inflammation without sepsis
    2. systemic inflammation and normal renal function
    3. AKI II or III without systemic inflammation
    4. post-surgery with normal renal function and without SIRS or an infection

Exclusion Criteria:

  • Renal transplant patients
  • Patients on immunosuppressive drugs (except steroids)
  • Patients with haematological malignancy
  • Jehovah's witness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
AKI with SIRS
Patients with AKI stage II or III and systemic inflammation without sepsis
Other: AKI
development of immune dysregulation and rise in inflammatory markers and activation of immune cells
AKI without SIRS
Patients with AKI stage II or III and no systemic inflammation
Other: AKI
development of immune dysregulation and rise in inflammatory markers and activation of immune cells
SIRS without AKI
Patients with systemic inflammation and normal renal function
Other: AKI
development of immune dysregulation and rise in inflammatory markers and activation of immune cells
No SIRS and no AKI
Patients after major surgery who do not have an infection, SIRS or AKI
Other: AKI
development of immune dysregulation and rise in inflammatory markers and activation of immune cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phenotypic characteristics and function of leukocytes
Time Frame: 7 days
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences in phenotypic characterisation and function of neutrophils between AKI stage II and III.
Time Frame: 7 days
7 days
Differences in phenotypic characterisation and function of neutrophils between AKI and no AKI
Time Frame: 7 days
7 days
Differences in cytokine profiles between AKI + SIRS and AKI without SIRS
Time Frame: 7 days
7 days
Differences in cytokine profiles between SIRS + AKI and SIRS without AKI
Time Frame: 7 days
7 days
Correlation between microRNA levels in patients with AKI and renal recovery
Time Frame: 7 days
Correlation between microRNA levels in patients with AKI and patient outcome Differences in cytokine profiles between AKI patients without systemic inflammation and patients without AKI and without systemic inflammation / infection.
7 days
Correlation between microRNA levels in patients with AKI and patient outcome
Time Frame: 7 days
Differences in cytokine profiles between AKI patients without systemic inflammation and patients without AKI and without systemic inflammation / infection.
7 days
Differences in cytokine profiles between AKI patients without SIRS and patients without AKI and without SIRS
Time Frame: 7 days
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guy's and St Thomas' NHS Foundation Trust

Collaborators

King's College London

Investigators

  • Principal Investigator: Marlies Ostermann, Guy's & St Thomas NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2013

Primary Completion (Actual)

August 1, 2022

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

June 10, 2015

First Submitted That Met QC Criteria

June 11, 2015

First Posted (Estimated)

June 12, 2015

Study Record Updates

Last Update Posted (Estimated)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSP88220

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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