Abstract
BackgroundAcute kidney injury (AKI) subtypes combining kidney functional parameters and injury biomarkers may have prognostic value. We aimed to determine whether neutrophil gelatinase-associated lipocalin (NGAL)/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) defined subtypes are of prognostic relevance in cardiac surgery patients.MethodsWe studied 198 higher-risk cardiac surgery patients. We allocated patients to four groups: Kidney Disease Improving Global Outcomes (KDIGO)-AKI-negative and NGAL/hepcidin-25 ratio-negative (no AKI), KDIGO AKI-negative and NGAL/hepcidin-25 ratio-positive (subclinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-negative (clinical AKI), KDIGO AKI-positive and NGAL/hepcidin-25 ratio-positive (combined AKI). Outcomes included in-hospital mortality (primary) and long-term mortality (secondary).ResultsWe identified 127 (61.6%) patients with no AKI, 13 (6.6%) with subclinical, 40 (20.2%) with clinical and 18 (9.1%) with combined AKI. Subclinical AKI patients had a 23-fold greater in-hospital mortality than no AKI patients. For combined AKI vs. no AKI or clinical AKI, findings were stronger (odds ratios (ORs): 126 and 39, respectively). After adjusting for EuroScore, volume of intraoperative packed red blood cells, and aortic cross-clamp time, subclinical and combined AKI remained associated with greater in-hospital mortality than no AKI and clinical AKI (adjusted ORs: 28.118, 95% CI 1.465–539.703; 3.737, 95% CI 1.746–7.998). Cox proportional hazard models found a significant association of biomarker-informed AKI subtypes with long-term survival compared with no AKI (adjusted ORs: pooled subclinical and clinical AKI: 1.885, 95% CI 1.003–3.542; combined AKI: 1.792, 95% CI 1.367–2.350).ConclusionsIn the presence or absence of KDIGO clinical criteria for AKI, the urinary NGAL/hepcidin-25-ratio appears to detect prognostically relevant AKI subtypes.Trial registration numberNCT00672334, clinicaltrials.gov, date of registration: 6th May 2008, https://clinicaltrials.gov/ct2/show/NCT00672334.Graphic abstractDefinition of AKI subtypes: subclinical AKI (KDIGO negative AND Ratio-positive), clinical AKI (KDIGO positive AND Ratio-negative) and combined AKI (KDIGO positive AND Ratio-positive) with urinary NGAL/hepcidin-25 ratio-positive cut-off at 85% specificity for in-hospital death. AKI, acute kidney injury. AUC, area under the curve. NGAL, neutrophil gelatinase-associated lipocalin. KDIGO, Kidney Disease Improving Global Outcomes Initiative AKI definition.
Highlights
Acute kidney injury (AKI) is an independent risk factor for morbidity and mortality after cardiac surgery [1]
Acute kidney injury events, such as hypoxia, inflammation or toxins like catalytic iron may harm different kidney compartments, consensus Kidney Disease Improving Global Outcomes (KDIGO) [2] criteria for AKI are still based on filtration-function related parameters
Volume of intraoperative packed red blood cells, aortic cross-clamp time and concentrations of plasma lactate and urinary neutrophil gelatinase-associated lipocalin (NGAL)/hepcidin-25 ratio at the end of surgery were higher in patients with AKI
Summary
Acute kidney injury (AKI) is an independent risk factor for morbidity and mortality after cardiac surgery [1]. The combination of classical renal function parameters with biomarker levels, e.g., kidney injury molecule-1, interleukin 6, midkine and neutrophil gelatinase-associated lipocalin (NGAL), has led to the introduction of the concept of biomarker-based subtypes of AKI [3,4,5,6,7,8,9]. Some of these biomarkers may be relevant to cardiac surgery patients undergoing cardiopulmonary bypass. Trial registration number NCT00672334, clinicaltrials.gov, date of registration: 6th May 2008, https://clinicaltrials.gov/ct2/show/NCT00672334
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