Acute Kidney Injury After Cardiac Surgery (NEPHROCAR)

Impact of the Early Hemodynamic Evaluation Guided by Urinary Biomarkers on the Acute Kidney Injury After Cardiac Surgery

Acute kidney injury (AKI) is common after cardiac surgery. The diagnosis is based on the criteria defined by the Kidney Disease Improving Global Outcomes (KDIGO) classification: oliguria and elevation of serum creatinine. However, oliguria is not specific of AKI and elevation of serum creatinine is too late. Therefore, new methods have been developed to earlier assess the risk of AKI.

Among those methods, it has been shown that the increase of urinary dosage, in the hours following the surgery, of two proteins (Tissue Inhibitor of Metallo-Protease 2 (TIMP2) and Insulin Growth Factor Binding Protein 7 (IGFBP7)) is associated with an increased risk of occurrence of AKI in patients hospitalized in intensive care unit. The Nephrocheck® test combines the urinary dosage of those two proteins TIMP2 and IGFBP7.

Insofar as post-surgery low cardiac output is one curable cause of AKI, the early detection of early kidney risk allows corrective measures to stabilize hemodynamic state and thus to reduce the risk of AKI.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Cardiac Surgery
• Intervention / Treatment: Procedure: Standard clinical routine; Procedure: Nephrocheck test

Detailed Description

The usual diagnostic markers of AKI are defaulted. Indeed, oliguria tends to overstate the impact of AKI, up to 40-50% of patients. Postoperative increased serum creatinine is a late marker for the AKI. Furthermore, perioperative hemodilution and serum creatinine kinetic delay the postoperative peak of serum creatinine from 48 to 72 h.

Nephrocheck® test combines the urinary dosage of 2 proteins (TIMP2 and IGFBP7). These 2 proteins are excreted by the tubular cell in case of suffering whatever the origin, for example tissue hypoxia by low renal blood flow or a systemic inflammatory response. In a medical ICU, the test performed within 4 to 12 hours after kidney aggression can predict the onset of persistent AKI beyond 4 weeks.

Until randomization, all patients are treated according to the standard of care for the center. This includes a blood test upon arrival in the intensive care unit and continuous monitoring of vital parameters.

• Study Type: Interventional
• Enrollment (Actual): 848
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35000
    • Rennes University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• On-pump cardiac surgery ;
• Informed and written consent of the patient or inclusion according to the emergency procedure;
• Affiliated patient or beneficiary of a social protection

Exclusion criteria:

• Left and / or right ventricular assist device;
• Heart transplant;
• Chronic kidney disease with renal replacement therapy before surgery;
• Hemorrhagic shock requiring surgical hemostasis at the time of randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Standard clinical routine	Procedure: Standard clinical routine; Patient management is carried out according to the usual service protocol
Experimental: Nephrocheck group; Nephrocheck test	Procedure: Nephrocheck test; Nephrocheck® test is realized 4 hours after the end of the cardiopulmonary bypass; If the test is positive, hemodynamic evaluation is carried out and adapted therapy to result of this evaluation is initiated.; If the test is negative, patient management is carried out according to the usual protocol.; A second test is realized 6 hours after the first test whatever the result of it.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of an AKI according to the KDIGO classification without oliguria	According to the KDIGO classification: Stage 1; Increase in serum creatinine ≥ 26.5 μmol / l or 1.5 to 1.9 times baseline serum creatinine Stage 2; Increase in baseline serum creatinine from 2.0 to 2.9 times Stage 3; An increase of 3.0 times the baseline serum creatinine or serum creatinine ≥ 354 μmol / l or initiation of renal replacement therapy	72 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Filling solute volumes	Recording of the filling solute volumes administered within 48 hours postoperatively	48 hours after surgery
Use of catecholamin	Recording (YES/NO) of the recourse of catecholamin required during the medical care, within 48 hours postoperatively	48 hours after surgery
Special extra corporeal circulation	Recording (YES/NO) of the recourse of a particular extracorporeal system within 48 hours postoperatively : Extracorporeal Life Support, heart pumps (Impela® like devices), or Intra-aortic balloon pump.	48 hours after surgery
Duration of stay in the ward		Up to 28 days post surgery
Oliguria	Proportion of patients with an oliguria defined according to the KDIGO criteria : Stade 1 ; diuresis < 0.5 mL/kg/h for 6 à 12 h; Stade 2 ; diuresis < 0.5 mL/kg/h for more than 12h; Stade 3 ; diuresis < 0.3 mL/kg/h for more than 24h or anuria ≥ 12h ;	48 hours after surgery
Repeatability of the Nephrocheck® test	Only for the patients in the Nephrocheck arm, variations between pre and postoperative Nephrocheck® test results will be assessed	10 hours post surgery
Mortality rate	Mortality rate in the ward	Up to 28 days post surgery

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Collaborators: JRAR Association
• Investigators: Principal Investigator: Sébastien BIEDERMANN, MD, CHU Rennes

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2018
• Primary Completion (Actual): September 16, 2021
• Study Completion (Actual): September 16, 2021

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 11, 2018

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Urinary biomarkers
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: 35RC17_8822; 2017-A01935-48 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No