TIMP2*IGFBP7 and Transient AKI (BIOCHECK)

Does the Urine Concentration of TIMP2*IGFBP7 Can Distinguish Patients Who Will Present Transient or Persistent Acute Kidney Injury During Septic Shock? A Retrospective Analysis. BIOCHECK

Patients with septic shock in the intensive care unit have a high risk to develop acute kidney injury (AKI) and AKI is an independent risk factor of mortality. Given the absence of validated pharmacological treatments for limiting the progression of AKI or for accelerating recovery from AKI, early intervention and the restoration of the glomerular filtration rate (GFR) in this context of septic shock might improve the patients' prognosis. One major challenge is to determine whether or not the AKI is reversible (return to normal function KDIGO 0 within 72 hours). In this retrospective study the investigators will analyze all patients admitted for a septic shock in three French ICUs between the 1st january 2014 and 01st January 2017 who developed an AKI (KDIGO ≥1) at admission and who had a determination of the urine concentration of TIMP2*IGFBP7 at admission. The investigators will determine the best threshold of TIMP2*IGFBP7 to distinguish the population of patients who will return to normal kidney function within 72 hours (KDIGO 0).

Study Overview

• Status: Recruiting
• Conditions: Septic Shock

Detailed Description

Background :

Patients with septic shock in the intensive care unit have a high risk to develop acute kidney injury (AKI). AKI is an independent risk factor of mortality. Given the absence of validated pharmacological treatments for limiting the progression of AKI or for accelerating recovery from AKI, early intervention and the restoration of the glomerular filtration rate (GFR) in this context of septic shock might improve the patients' prognosis. One major challenge is therefore how to determine whether or not the AKI is reversible. The best-studied biomarkers (NGAL and KIM 1) have little discriminant power in septic patients because of their poor specificity or unsuitable kinetics for very early diagnosis. The combination of urine assays for tissue inhibitor of metalloproteinase 2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7) has shown good diagnostic performance for the very early detection of the risk of developing AKI in the following 12 hrs. Urine levels of these two markers specifically reflect damage to kidney tubules. Moreover, the levels appear to be strongly correlated with the severity of tubule damage. Thus, one can reasonably hypothesize that measurement of these markers in the very early stages of septic shock might determine the presence and severity of kidney tubule damage. A threshold (yet to be defined) would help to differentiate between (i) transient, non-severe injury and (ii) injury that is already too severe to be reversible.

Purpose : to determine whether or not the urine concentration of TIMP2*IGFBP7 may distinguish patients with high risk of persistent or transient AKI during the early phase of septic shock.

• Study Type: Observational
• Enrollment (Estimated): 170

Contacts and Locations

• Study Contact: Name: Julien Maizel, Pr; Phone Number: +33 3 22 08 78 07; Email: maizel.julien@chu-amiens.fr

Study Locations

• France
  • Amiens, France, 80000
    • Recruiting
    • CHU Amiens-Picardie
    • Contact: Julien Maizel, Professor; Phone Number: +33 3 22 08 78 07; Email: maizel.julien@chu-amiens.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

univariate comparison between the 2 groups (transient and persistent AKI) using Mann Whithney test or Chi square test. ROC curve analysis to determine the best threshold of TIMP2*IGFBP7 groups to distinguish the 2 groups.

Description

Inclusion Criteria:

• Age 18 or over
• Inclusion criteria: septic shock (according to Bone's criteria) within 4 hours following the introduction of catecholamines, AKI defined by KDIGO≥1, social security coverage, measurement of the urine concentration of TIMP2*IGFBP7 within the 4 hours following the introduction of catecholamines, patients admitted for a septic shock between 1st January 2014 and 1st January 2017 in the medical ICU of Amiens university hospital France, medical ICU of Montpellier university hospital France and ICU Melun hospital, France

Exclusion Criteria:

• Need for immediate renal replacement therapy, anuria, chronic renal failure (stage 4 or 5 with GFR<30ml/min), obstructive AKI, pregnancy, cardiac arrest during the same hospitalization, life expectancy<48 hours, Child C Cirrhosis, prior occurrence of AKI during the current hospital stay, kidney transplantation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KDIGO value	: Transient AKI defined by the return to KDIGO 0 within the first 72 hours following the introduction of catecholamines	return to KDIGO 0 within the first 72 hours following the introduction of catecholamines

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
need for renal replacement therapy	need for renal replacement therapy within the first 72 hours following the introduction of catecholamines	within the first 72 hours following the introduction of catecholamines

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Septic shock; Acute kidney injury; TIMP2*IGFBP7
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: PI2018_843_0013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No