There is no specific therapy for acute kidney injury. It is presumed that supportive measures improve the care and outcome of patients with acute kidney injury. The investigators hypothesize that the implementation of a bundle of supportive measures adapted to patients undergoing major surgery reduces the occurrence of AKI. This randomized prospective multicenter trial is needed to investigator whether the implementation of the bundle of measures is effective to prevent AKI in high risk patients undergoing major surgery.
In earlier studies, interventions to treat acute kidney injury (AKI) were started after a functional damage of the kidneys was already established. However, none of the interventions had an effect in treating AKI. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines recommend implementing different measures in patients at high risk for AKI, but the evidence that the implementation of the bundle (consisting of optimization of hemodynamics and perfusion pressure, avoidance of nephrotoxins and hyperglycemia) can prevent AKI is very weak. Biomarkers can be used to identify patients at high risk for AKI after surgery (prior to the development of AKI). The cell-cycle arrest biomarkers, Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) and Insulin-like growth factor-binding protein 7 (IGFBP7), have been demonstrated to have the best predictive performance for the development of AKI after surgery as compared to other biomarkers. In addition, these biomarkers are not influenced by different co-morbidities or other clinical situations. In the BigpAK1 trial, which was a single-center trial, the authors investigated whether a biomarker-guided implementation of the KDIGO guidelines can reduce the occurrence of AKI in patients undergoing major non-cardiac surgery. The results demonstrate that the implementation of the KDIGO bundle in high risk patients for AKI (\[TIMP-2\]\*\[IGFBP7\] between 0.3 and 2) significantly reduced the occurrence of AKI compared to the standard of care group. However, this was a single center trial which needs to be confirmed in a large trial. Therefore, based on these data, a definitive, prospective, randomized controlled, multicenter study including 1302 surgical patients at high risk for AKI identified by \[TIMP-2\]\*\[IGFBP7\] will be performed. The goal of this trial is to investigate the effect of the implementation of the KDIGO bundle in patients at high risk for AKI after major surgery compared to standard of care in the same patient population. This biomarker-guided approach (individualized therapy) enables to treat patients at high risk for AKI prior to a functional damage of the kidneys.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
1,180
Implementation of the KDIGO bundle for at least 12 hours 1. discontinuation of all nephrotoxic drugs when possible 2. optimization of volume status and hemodynamic parameters (consideration of a functional hemodynamic monitoring) 3. close monitoring of serum creatinine, fluid balance and urinary output 4. avoidance of hyperglycemia 5. considerations of alternatives to radiocontrast agents 6. discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in the perioperative period 7. avoidance of HES, gelatin, and chlorid-rich solutions
Occurence of moderate or severe AKI
Time frame: 72 hours after start of intervention
Adherence to the implementation of the KDIGO-bundle
Number of patients in whom * Nephrotoxic agents were discontinued * Optimal volume status and perfusion pressure were ensured * The use of hemodynamic monitoring was considered * Serum creatinine and urine output were considered * Hyperglycemia was avoided * Alternatives to radiocontrast were considered
Time frame: 72 hours after start of intervention
Severity of AKI
Severity of AKI as defined by the KDIGO guidelines based on creatinine or urine output parameter: Stage 1 Creatinine: 1.5-1.9 times baseline OR \> 0.3 mg/dl (\> 26.5 mmol/l) increase and/or urine output \< 0.5 ml/kg/h for 6-12 hours Stage 2 Creatinine: 2.0-2.9 times baseline and/or urine output \< 0.5 ml/kg/h for \>= 12 hours Stage 3 Creatinine: 3.0 times baseline OR Increase in serum creatinine to \>= 4.0 mg/dl (\>= 353.6 mmol/l) OR Initiation of renal replacement therapy OR, In patients \< 18 years, decrease in eGFR to \< 35 ml/min per 1.73 m2 and/or urine output \< 0.3 ml/kg/h for \>= 24 hour
Time frame: 3 days after start of intervention
Changes in biomarker values
Difference between the 12 h after initial measuring and the initial measuring \[TIMP-2\]\*\[IGFBP7\] value
Time frame: 12 hours after start of intervention
Free-days of mechanical ventilation
Time frame: up to 3 days after start of intervention
Free-days of vasopressors
Time frame: up to 3 days after start of intervention
Need of renal replacement therapy
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Centre Hospitalier Universitaire de Clermont-Ferrand
Clermont-Ferrand, France
Service d´Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon
Lyon, France
Centre Hospitalier Universitaire de Reims
Reims, France
Department of Anaesthesiology and Intensive Care Medicine, Klinikum Bayreuth GmbH
Bayreuth, Germany
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus, Ruhr University Bochum
Bochum, Germany
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn
Bonn, Germany
Department of Anesthesiology, Intensive Care and Pain Medicine, Klinikum Dortmund
Dortmund, Germany
Department of Anesthesiology and Intensive Care Medicine, University Hospital "Carl Gustav Carus", Technische Universität Dresden
Dresden, Germany
Department of Anesthesiology, University Hospital Düsseldorf, Heinrich-Heine-University Duesseldorf
Düsseldorf, Germany
Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, University Duisburg-Essen
Essen, Germany
...and 27 more locations
Time frame: up to 30 days after start of intervention
Need of renal replacement therapy
Time frame: up to 90 days after start of intervention
Duration of renal replacement therapy
Time frame: up to 30 days after start of intervention
Duration of renal replacement therapy
Time frame: up to 90 days after start of intervention
Renal recovery
renal recovery is defined as complete recovery: serum creatinine levels \< 0.5 mg/dl higher than baseline serum creatinine (creatinine level before surgery), partial recovery: serum creatinine \> 0.5 mg/dl higher than baseline but not dialysis-dependence; non-recovery: patients who remained dialysis dependent
Time frame: up to 90 days after start of intervention
Mortality
Time frame: 30 days after start of intervention
Mortality
Time frame: 90 days after start of intervention
ICU and hospital stay
Time frame: up to 90 days after start of intervention (until discharge)
Major adverse kidney events (MAKE)
\- major adverse kidney events consisting of mortality, dialysis dependency persistent renal dysfunction (defined as serum creatinine ≥ 2x to baseline value at hospital discharge)
Time frame: up to 90 days after start of intervention