Biomarker-guided implementation of the KDIGO guidelines to reduce the occurrence of acute kidney injury in patients after cardiac surgery (PrevAKI-multicentre): protocol for a multicentre, observational study followed by randomised controlled feasibility trial

Abstract

Introduction: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial.

Methods and analysis: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes.

Ethics and dissemination: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial.

Trial registration number: NCT03244514.

Keywords: acute renal failure; adult intensive & critical care; cardiac surgery.

Conflict of interest statement

Competing interests: MM, JK and AZ have received lecture fees from Astute Medical, Fresenius and Baxter, unrelated to the current study. JK and AZ have received grant support from Astute Medical, unrelated to the current study. MO has received lecture fees from Biomerieux, Fresenius Medical and Baxter. CA has received lecture fees from Baxter. LF has received research funding from Baxter and Ortho Clinical Diagnostics, consultancy fees from Medibeacon/La Jolla Pharmaceuticals and honoraria from Biomerieux/Astute.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Trial workflow. Patients will be screened in all participating sites for eligibility on a daily basis. Prior to enrolment, it is assured that none of the exclusion criteria are present and informed consent process is performed. Four hours after cardiopulmonary bypass (CPB), urine samples for the measurement of tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2]*[IGFBP7] will be collected. In case [TIMP-2]*[IGFBP7] is ≥0.3, patients are at high risk and randomisation can be performed. Patients in the intervention group will receive a functional haemodynamic monitoring (according to the routine of each centre) immediately after randomisation and haemodynamic situation will be optimised according to a haemodynamic algorithm (figure 2). Laboratory test will be analysed and variables relevant for the assessment of renal and haemodynamic situation and safety will be recorded. Follow-up will be performed after 30, 60 and 90 days. ACEi, ACE inhibitors; AKI, acute kidney injury; ARBs, angiotensin receptor blockers; eGFR, estimated glomerular filtration rate; HES, hydroxyethyl starch; KDIGO, Kidney Disease: Improving Global Outcomes; RRT, renal replacement therapy; SCr, serum creatinine.

Figure 2

Haemodynamic algorithm of the intervention group. Patients of the intervention group will receive a functional haemodynamic monitoring and an optimisation according to a haemodynamic algorithm consisting of three steps which need to be checked every 3 hours: step 1—performance of the passive leg raising test. If the cardiac output (CO) increases by >10%, then volume has to be supplemented (crystalloids 500–1000 mL according to the treating intensivist). If CO is ≤10%, step 2—measurement of the cardiac index (CI). If the CI is 2, then dobutamine or epinephrine (according to the treating intensivist) needs to be applied. If CI is >2.5 L/min/m2, then step 3—measurement of mean arterial pressure (MAP). If the MAP is <65 mm Hg, then norepinephrine needs to be adjusted. If MAP is >65 mm Hg, then the goal is achieved. This is checked every 3 hours up to 12 hours after randomisation. PLRT, passive leg raising test.