Can Nephrocheck™ Predict the Reversibility of Early, Acute Kidney Injury During Septic Shock?

Patients with septic shock in the intensive care unit have an elevated risk of developing acute kidney injury (AKI). AKI is an independent factor for mortality. Interventions that limit the worsening of renal function might have an impact on the mortality rate in these patients. 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 hemodynamic change during the initial phase 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.

Inclusion criteria

• Age 18 or over
• Septic shock (according to Bone's criteria) within 4 hours of introduction of catecholamines
• AKI, characterized by a KDIGO score ≥ 1
• Social security coverage

Exclusion criteria

• AKI requiring emergency RRT (in the critical care physician's opinion).
• Anuria
• Stage 4-5 chronic kidney failure with a GFR below 30 ml/min.
• Rapidly progressing renal disorders (glomerulonephritis, HUS, blockage, etc.)
• Obstructive AKI
• Probable glomerular damage (nephritic syndrome, nephrotic syndrome, chronic glomerulonephritis)
• Pregnancy or breastfeeding
• Legal guardianship or lack of social security coverage.
• Cardiocirculatory arrest
• Life expectancy <48 hours.
• Child C cirrhosis
• Prior occurrence of AKI during the current hospital stay
• Transplantation
• Subject participating in another study with an exclusion period ongoing at the time of the pre-inclusion