Prevention of Cardiac Surgery–Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial

Abstract

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR −4.8% [95% CI, −16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group. (Anesth Analg XXX;XXX:00-00) KEY POINTS• Question: Is it feasible to implement a bundle of supportive measures in high-risk patients undergoing cardiac surgery in a multinational setting? • Findings: In this multicenter randomized clinical trial, we found that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) bundle is feasible in a multinational setting and that these supportive measures significantly reduced the occurrence of moderate and severe acute kidney injury (AKI). • Meaning: The findings underpin the need for a definitive trial to evaluate whether the KDIGO bundle reduces the occurrence of AKI in high-risk patients after cardiac surgery.

Prompting With Checklist for Early Recognition and Treatment of Acute Illness On The Prevention of Acute Kidney Injury in Patients With Septic Shock

“…These results are consistent with the studies that evaluated KDIGO care bundles in patients after cardiac surgery and major surgery. 14,20,21 It is noteworthy that the implementation of the Surviving Sepsis Campaign and KDIGO care bundles improved the short-and long-term outcomes of sepsis and AKI, respectively. 22,23 However, in clinical practice, these interventions have been shown to have poor performance.…”

Urine Sediment Exam Provides More Diagnostic Information in AKI than Novel Urinary Biomarkers: CON

“…Unlike microscopic urinalysis, many novel urinary biomarkers have been shown to identify patients prior to the presence of clinical AKI, but perhaps more importantly they have been consistently linked with adverse patient outcomes and have been shown to help improve outcomes when acted on. [7][8][9][10] For example, in the Schinstock ER study, a urine neutrophil gelatinase associated lipocalin (uNGAL) ≥42.7 ng/ml provided a higher sensitivity (64.5%) and a PPV on par with that of RTEs and granular casts. 6 Improved sensitivity for detecting AKI allows clinicians to implement renal-protective measures prior to the development of advanced renal damage and can prevent severe AKI and its complications.…”

“…There have been several studies which randomized patients at risk for AKI to receive kidney-focused care bundles using urinary Tissue inhibitor metalloprotease-2 and insulin-like growth factor binding protein 7 (TIMP-2 and IGFBP-7) ≥0.3 as part of the enrollment criteria. 7,9,10 Those who received these KDIGO guideline-based care bundles, which include management of hemodynamic status (intravenous fluids, inotropes and/or vasopressors), glycemic control, avoidance of nephrotoxins, and potentially nephrology consultation, had lower rates of moderate-severe AKI as well as shorter stays in the ICU and hospital. 7,9 These biomarkers may be helpful for the identification of the highest risk patients who are likely to benefit from intense, costly, and time-consuming supportive care that may be difficult and impractical to deliver to all patients.…”

Biomarkers in Cardiorenal Syndrome

“…Moreover, the accuracy of TIMP2 and IGFBP7 in predicting the occurrence of AKI is greater than those of KIM-1, NGAL, L-FABP, IL-18, or Cystatin C [96][97][98]. Finally, results of the PrevAKI randomized trial have shown that the product of IGFBP7 and TIMP-2 by guiding KDIGO recommended monitoring and treatments can allow a reduction in the incidence of post-cardiac AKI [99].…”