Validation of a Urinary Biomarker as Diagnostic Tool for AKI in Sepsis

NCT01981993 | Completed

• 1 other identifier: 2009/048
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND: Early diagnosis and prognostication of acute kidney injury in patients with sepsis is key to further our understanding this disease and in the evaluation of new interventions for this condition. Many urinary biomarkers have been proposed, but no single one seems to consistently provide additional information on top of clinical and routine biochemical parameters. Some authors have proposed to use a panel of urinary biomarkers to increase the accuracy However, this approach has so far not been tested in a large group of patients with sepsis. In addition, newer and more performant analytical techniques have been developed that warrant testing in the clinical field. PATIENTS AND METHODS: At least 150 consecutive patients admitted to a tertiary care intensive care unit (ICU) with sepsis will be included. After bladder catheterisation, urinary samples will be collected at time points 0, 4 hours and 24 hours after admission, and further daily on day 1-5. Samples will be immediately centrifuged and frozen at -80°C until analysis. Samples will be extracted by removing larger proteins (\>20kDa) and de-salting step prior to mass spectrometry analysis. Investigators will use capillary electrophoresis-mass spectrometry (CE-MS) to assess urinary peptides predictive of AKI: 20 peptides constituting the AKI marker pattern previously established from a cohort of ICU patients. Simultaneously, samples will be analysed using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS), an alternative platform to CE-MS, which is currently being developed for routine ICU use. A proof of concept of the technique involved has been successfully applied to a set of urine samples from patients diagnosed with diabetes presenting normoalbuminuria (controls) and macroalbuminuria (cases). Clinical, demographic and biochemical data of patients will be collected during the first 5 days. PATIENT OUTCOME

• in the short term:
• development of acute kidney injury according to RIFLE criteria
• death
• need for renal replacement therapy during ICU stay
• on the longer term
• death
• need for renal replacement therapy
• estimated glomerular filtration rate as calculated by MDRD at 3 months, 1 year and 2 years. Using cut-offs , Receiver Operating Characteristics curves, negative and positive predictive value will be used to describe diagnostic performance of the biomarker panel alone, or in combination with basic clinical and/or routine biochemical parameters. Univariate and multivariate logistic regression for death will be used to evaluate prognostication value of the biomarker set. In addition, new discriminatory cut-offs of proteomic patterns as determined by more recent proteomic analysis techniques will be determined in a training set (half of the cohort) and validated in the other half of the cohort. Using the MALDI-TOF MS platform, investigators will assess urinary peptides that were predictive of AKI in a training set (ca. 75 patients) with good diagnostic performance of the marker panel (accuracy above 0.8) . Performance of the biomarker panel will be assessed in a blinded test set of ca. 75 patients to evaluate validity of the model in AKI detection.

Conditions

Sepsis at Intensive Care Unit

Outcome Measures

Primary Outcomes (1)

• development of acute kidney injury according to RIFLE criteria

  at 3 months after inclusion

Secondary Outcomes (3)

• change in need for renal replacement therapy

  at 3 months - 1 year and 2 year after inclusion

• change in estimated glomerular filtration rate as calculated by MDRD

  at 3 months, 1 year and 2 years after inclusion

• death

  1 year and 2 years after inclusion

Study Arms (1)

patients at ICU with sepsis

Biological: Urinary proteomic analysis

Interventions

Urinary proteomic analysis BIOLOGICAL

patients at ICU with sepsis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

consecutive patients admitted to a tertiary care intensive care unit (ICU) with sepsis

You may qualify if:

• sepsis at ICU

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

urine samples for proteomic analysis

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 13, 2013
• Study Start: June 4, 2009
• Primary Completion: March 27, 2011
• Study Completion: March 27, 2011
• Last Updated: May 3, 2023

Record last verified: 2023-05

Locations

BE (1)