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.

Inclusion Criteria:

• Patients after major surgery who need to be admitted to the ICU

• Age > 18 years

• [TIMP-2]*[IGFBP7] ≥ 0.3 4-18 hours after surgery

• Inserted jugular central venous line and a urinary catheter

• Written informed consent.

• At least one additional risk factor for AKI

  1. Age > 75 years
  2. Critical illness such as ongoing requirement of vasopressor support and/or mechanical ventilation postoperatively
  3. Pre-existing chronic kidney disease (eGFR<60ml/min)
  4. Intraoperative use of radio contrast agents.

Exclusion Criteria:

• Pregnancy or breastfeeding
• Pre- existing high stages of chronic kidney disease (stage 4 or 5 i.e. eGFR < 15 ml/ min)
• Kidney transplant within the last 12 month
• Known (Glomerulo-) Nephritis, interstitial nephritis or vasculitis
• Anuria at inclusion time
• Preexisting AKI
• Renal replacement therapy (RRT) within the last 90 days
• Indication for renal replacement at the time of inclusion
• Participation in another intervention trial that investigates a drug/intervention that affects kidney function
• Persons held in an institution by legal or official order
• Persons with any kind of dependency on the investigator or employed by the responsible institution or investigator