Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

Abstract

Introduction: Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.

Methods and analysis: The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.

Ethics and dissemination: The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.

Trial registration number: NCT04647396.

Keywords: Acute renal failure; Adult intensive & critical care; Chronic renal failure; INTENSIVE & CRITICAL CARE; SURGERY.

Figure 1

Trial workflow. AKI, acute kidney injury; APACHE, Acute Physiology and Chronic Health Evaluation; BUN, blood urea nitrogen; CVP, central venous pressure; ECMO, extracorporeal membrane-oxygenation; eGFR, estimated glomerular filtration rate; ICU, intensive care unit; IGFBP7, insulin like growth factor binding protein 7; KDIGO, Kidney Disease Improving Global Outcomes; MAKE, major adverse kidney events; NYHA, New York Heart Association; POD, post-operative day; RRT, renal replacement therapy; SOFA, sepsis-related organ faiulre assessment; TIMP-2, tissue inhibitor of metalloproteinases 2.

Figure 2

Overview of study visits. AKI, acute kidney injury; ARB, angiotensin receptor blockers; BMI, body mass index; ICU, intensive care unit; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes; MAKE, major adverse kidney events; MAP, map arterial pressure; RRT, renal replacement therapy.

Figure 3

Haemodynamic algorithm of the intervention group which will be performed at least every 3 hours during the 12 hours following randomisation. CI, cardiac index; CO, cardiac output; MAP, mean arterial pressure.