Clinical trial NCT03472079: TIMP2*IGFBP7 and Transient AKI
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Septic Shock
Keywords: Acute kidney injury
Septic shock
TIMP2*IGFBP7
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2018-03-21
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: KDIGO value
timeFrame: return to KDIGO 0 within the first 72 hours following the introduction of catecholamines
Secondary outcomes:
measure: need for renal replacement therapy
timeFrame: within the first 72 hours following the introduction of catecholamines
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens-Picardie
Study officials:
References: