Acute Kidney Injury - Biomarkers in Major Abdominal Surgery

NCT ID: NCT04582747

Last Updated: 2020-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-07-03

Study Completion Date

2020-03-03

Brief Summary

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To validate Urinary Biomarkers for the prediction of AKI in major abdominal surgery patients

Detailed Description

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Background

Surgery is a risk factor for acute kidney Injury (AKI). Surgery exposes patients to hypotension, sepsis, the infusion of blood products, ischaemia, oxidative stress and reperfusion injury.

Patients who develop AKI post operatively are susceptible to fluid overload, infections, and cardiac events. AKI confers an increased risk of chronic kidney disease and mortality. Studies assessing rates of AKI in general surgical patients place the frequency at 1-14%.

Established methods of assessing for AKI - products of nitrogen breakdown and urine output - have limitations. Serum creatinine and urea are affected by sex, nutritional status, blood in the gastrointestinal tract, and fluid resuscitation. Rises in serum creatinine become apparent once glomerular filtration has reduced by half. This potentially delays the use of reno-protective strategies.

Novel biomarkers have been investigated. These aim to verify the use of renal biomarkers as a method of identifying AKI more rapidly: It is hoped that reno-protective strategies could be adopted sooner.

Much work has concerned cardiac and transplant surgery. AKI rates have been quoted as high as 30% in this cohort. Results were initially encouraging for various biomarkers. One biomarker (Insulin like growth factor binding protein number 7 / Tissue inhibitor of metalloproteinases 2 - IGFBP-7/TIMP-2) has therefore been incorporated into Enhanced Recovery Programmes in such patients.

While research in cardiac and transplant surgery has been extensive, it has been limited with regards to abdominal surgery. Although rates of AKI are lower in this cohort, they still bear a significant burden of disease. At present, no biomarker has been found to be clinically useful in this setting.

Study Objectives

Primary

The validation of Urinary Biomarkers for use in the prediction of AKI in major abdominal surgery patients

Secondary

To assess the role different surgical sub-types and peri-operative factors have in causing AKI in Major Abdominal Surgery patients

Trial design

This is an observational study that will assess the use of Urinary biomarkers against conventional methods of assessing for AKI, the Kidney Disease, Improving Global Outcomes (KDIGO) criteria. The KDIGO criteria is based on increases in serum creatinine and reduction in urine output.

The biomarkers are:

IGFBP-7/TIMP-2 Neutrophil Gelatinase Associated Lipocalin (NGAL) Kidney Injury Molecule 1 (KIM-1) Dickkopf related protein 3 (DKK-3)

All patients undergoing major elective general surgery, and major abdominal gynaecological surgery will be included. All patients will have a urine sample taken 4 hours post operatively. This sample will be tested using the biomarkers. Written consent will be obtained from all participants.

The consent form has been designed with help of 10 surgical inpatients and 4 surgical nurses to ensure ease of understanding and a lack of medical jargon.

No changes are required to standard patient care. The urine sample obtained will be a catheter specimen.

Comparison of the novel biomarkers against conventional methods will be conducted using the KDIGO criteria. This entails regular urine output measurement, assessment of blood urea, electrolytes, and estimated glomerular filtration rate. Data regarding patient, operative and post-operative characteristics will be recorded on a purpose-built secure hospital intranet database.

Data Analysis

Performance of the biomarkers will be assessed using multiple logistic regression, and by conducting 'area under the receiver-operator curve (AUROC)' analysis. A risk prediction model will be created based on patient factors strongly associated with the primary endpoint. The performance of the risk prediction model will be assessed as a standalone test and in conjunction with the novel biomarker tests.

The sample size was calculated on the basis of previously published AUROC values for the test, the expected prevalence of AKI, and a desire for a 95% confidence interval around the calculated AUROC estimate for the study. This results in a target sample size of 471.

Hoped Aims of Research

The researchers hope that a novel test is found that can identify AKI sooner in an at-risk cohort of patients. If so, a further trial is intended: post-operative patients who are positive to the novel test will be randomised to a kidney protective 'bundle', and rates of AKI compared.

Ultimately, the intention is to greatly reduce a significant cause of post-operative morbidity, surgical complications, and mortality, through the judicious use of a non-invasive test.

Conditions

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Acute Kidney Injury

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Major abdominal Surgery patients

Major Abdominal Surgery Patients

Urinary Biomarkers (NGAL, DKK-3, IGFBP-7/TIMP-2, KIM-1)

Intervention Type DIAGNOSTIC_TEST

Validation of Urinary biomarker tests for the rapid prediction of AKI.

No intervention is being proposed as part of the study. Concentrations of Urinary biomarkers will be obtained post operatively. These concentrations will be assessed to ascertain their predictive ability for the development of Acute Kidney Injury post-operatively.

Interventions

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Urinary Biomarkers (NGAL, DKK-3, IGFBP-7/TIMP-2, KIM-1)

Validation of Urinary biomarker tests for the rapid prediction of AKI.

No intervention is being proposed as part of the study. Concentrations of Urinary biomarkers will be obtained post operatively. These concentrations will be assessed to ascertain their predictive ability for the development of Acute Kidney Injury post-operatively.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* • Patients aged over 18 undergoing major Hepatobiliary, Oesophagogastric, Colorectal or abdominal Gynaecological Surgery at the Royal Surrey County Hospital. Patients undergoing Liver Transplant Surgery at King's College Hospital

* Be able to provide informed consent

Exclusion Criteria

* Patients requiring renal replacement therapy prior to the study
* Patients with pre-operative AKI
* Patients without baseline creatinine measurements
* Day case surgery
* Patients unable to consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Royal Surrey County Hospital NHS Foundation Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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AKI-BioMAS

Identifier Type: -

Identifier Source: org_study_id

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