Aims & Objectives
The primary end-point of the study was recently reported and published . It was the RIFLE-defined AKI rate (criteria definition - 50% increase in pre-op “baseline” serum creatinine within first 3 days of surgery) comparing patients managed with the RG system to controls. Baseline serum creatinine level was defined as latest serum creatinine level available prior to surgery. Secondary objectives included changes in plasma NGAL levels (Bioporto Diagnostics, Hellerup, Denmark) at 6-hours post-CPB as well as pre-CPB NGAL levels and post-operative complications.
This study (KIDNEY) was reviewed and approved by the Institutional Research Committee (16CARD13) prior to seeking Ethical committee (16/NI/0246, 2nd December 2016) approval and was registered on ClinicalTrials.gov website (NCT02974946). The study was also supported by the National Institute of Healthcare Research, Clinical Research Network, United Kingdom (NIHR ID: 32769). All recruited patients gave written informed consent to partake in the study. Trial patients were treated according to the Declaration of Helsinki 2013.
Patients with one (or more) of the following risk factors for AKI were recruited for this study: (i) diabetics (insulin or non-insulin dependent diabetes mellitus), (ii) haemoglobin level of 12.5 g/dl or below, (iii) Logistic Euroscore of 5 or above, (iv) estimated glomerular filtration rate (eGFR) of 20-60 mL/min/1.73 m² and (v) cardiac procedures when CPB-time was likely to exceed 120 minutes. Recruited patients underwent one of the following procedures: isolated coronary artery bypass grafting (CABG), isolated valve surgery (aortic valve replacement - AVR, mitral valve replacement - MVR, mitral valve repair - MV repair) or combined procedures (CABG, AVR, MV repair, tricuspid valve repair, MVR, Cox-Maze IV atrial fibrillation ablation, ascending aorta replacement, aortic root surgery, left ventricular aneurysmectomy & myxoma surgery in various combinations)
Consented patients were randomized using sealed opaque envelopes system generated by a research independent person in the research & development department. Management of patients randomised to the RenalGuard® system has been previously described  and included instantaneously-matched balanced forced-diuresis with furosemide and intravenous rehydration with Hartmann’s solution. Patients in the control group were managed as per current medical practice without forced-diuresis with intravenous furosemide in the OR. Otherwise, the management of the patients was similar including the anaesthetic technique and cardiopulmonary bypass run including the need for inotropic support to maintain a MAP (mean arterial pressure) > 65mmHg. CPB-flow was maintained at cardiac index of 2.4 l/min/m2. Oxygen delivery (ecDO2i) and CO2 production (ecVCO2i) during the CPB were monitored using the System M4 (Spectrum Medical, Gloucester, UK). Post-operatively both groups of patients were transferred to CICU.
The NGAL levels were assessed from plasma (ethylene diamine tetra-acetic acid - EDTA - tube) collected prior to the start of cardiac surgery and at 6-hour post cessation of CPB while the patient was recovering on the CICU. Specimens were centrifuged at 2380 g for 10 minutes at 4oC on the day of receipt, to pellet cellular material and the supernatants aliquoted and stored at -80oC until analysed. The NGAL test was a quantitative particle-enhanced turbimetric immune-assay (PETIA) using the BioPorto Kit (BioPorto Diagnostics A/S, Gentofte, Denmark) and the Abbott Architect C16000 analyser (Abbott Diagnostics, Chicago, USA).
Power calculations & statistical analyses
Based on the data from the department’s cardiac surgery database and previous publications , 110 patients per group were deemed adequate to achieve the primary end-point (RIFLE defined AKI rate) with a power of 0.8 and an alpha of 0.05.
Categorical data are expressed as percentages and differences between the two groups assessed using the X2 test of independence. Continuous variables are expressed as mean (standard deviation - SD) or median (minimum, maximum) for normally and skewed distributed data respectively. Group comparison was carried out using two-tailed t-test or Mann-Whitney U test accordingly. Adopting a previously reported NGAL cut-off level (142 ng/ml) for AKI, binary logistic regression analysis was used to assess the beneficial effect of the RG system. The factors included in the model were age, gender, ethnic origin, history of diabetes, left ventricular ejection fraction, pre-operative creatinine level, pre-operative NGAL level, pre-op eGFR level, Log EuroScore, STS Score, study group (RG vs. control), CVP, MAP & lactate levels in OR prior to start of surgery, CPB duration, procedure performed, urine volume produced in OR, CVP, MAP & lactate levels on admission to CICU and blood transfusion. The tests were considered significant at p< 0.05. SPSS version 26.0 (IBM SPSS statistics 26) was used for statistical analyses.
Two patients who were randomized to RG group could not be catheterized per urethrally at the start of the operation and had a supra-pubic catheter inserted at the end of the procedure and hence were not connected to the RG system. Additionally, two patients in the RG group and one patient from the control group had their surgery cancelled and therefore did not have post-operative data. All patients’ data were analysed on an intention- to-treat basis.
Patients were recruited from 1st March 2017 to 4th September 2019 as shown in the Consolidated Standards of Reporting Trials (CONSORT) flow diagram (Figure 1).