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Title: | Urinary Neutrophil Gelatinase-Associated Lipocalin/Hepcidin-25 Ratio for Early Identification of Patients at Risk for Renal Replacement Therapy After Cardiac Surgery: A Substudy of the BICARBONATE Trial. | Austin Authors: | Elitok, Saban;Kuppe, Hermann;Devarajan, Prasad;Bellomo, Rinaldo ;Isermann, Berend;Westphal, Sabine;Kube, Johanna;Albert, Christian;Ernst, Martin;Kropf, Siegfried;Haase-Fielitz, Anja;Haase, Michael | Affiliation: | Medical Faculty Medical Faculty, Institute for Biometrics and Medical Informatics, Otto von-Guericke-University Magdeburg, Magdeburg, Germany Department of Cardiology, Brandenburg Heart Center, Immanuel Hospital, Bernau, Germany Medical Faculty, University Clinic for Cardiology and Angiology Diaverum Renal Care Center, Potsdam, Germany From the Department of Nephrology and Endocrinology, Ernst von Bergmann Hospital Potsdam, Potsdam, Germany Brandenburg Medical School Theodor Fontane, Neuruppin, Germany Faculty of Health Sciences Brandenburg, Potsdam, Germany Institute of Integrated Health Care Systems Research & Social Medicine, Otto von-Guericke-University Magdeburg, Magdeburg, Germany Department of Anesthesiology and Intensive Care, Helios Klinikum Leisnig, Leisnig, Germany Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia Intensive Care Department of Integrated Critical Care, Center for Integrated Critical Care, The University of Melbourne, Melbourne, Victoria, Australia Institute of Cardiac Thoracic Vascular Anesthesia and Intensive Care Medicine, German Heart Center Berlin & Charité-University Medicine Berlin, Berlin, Germany Department of Laboratory Medicine, Institute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostic, Leipzig University Hospital, Leipzig, Germany Department of Laboratory Medicine, Institute of Laboratory Medicine, Tertiary Hospital Dessau, Dessau-Roßlau, Germany Department of Nephrology and Hypertension, Cincinnati Children's Hospital, Cincinnati, Ohio |
Issue Date: | 20-Sep-2021 | Date: | 2021-09-20 | Publication information: | Anesthesia and analgesia 2021; 133(6): 1510-1519 | Abstract: | Acute kidney injury requiring renal replacement therapy (AKI-RRT) is strongly associated with mortality after cardiac surgery; however, options for early identification of patients at high risk for AKI-RRT are extremely limited. Early after cardiac surgery, the predictive ability for AKI-RRT even of one of the most extensively evaluated novel urinary biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), appears to be only moderate. We aimed to determine whether the NGAL/hepcidin-25 ratio (urinary concentrations of NGAL divided by that of hepcidin-25) early after surgery may compare favorably to NGAL for identification of high-risk patients after cardiac surgery. This is a prospective substudy of the BICARBONATE trial, a multicenter parallel-randomized controlled trial comparing perioperative bicarbonate infusion for AKI prevention to usual patient care. At a tertiary referral center, 198 patients at increased kidney risk undergoing cardiac surgery with cardiopulmonary bypass were included into the present study. The primary outcome measure was defined as AKI-RRT. Secondary outcomes were in-hospital mortality and long-term mortality. We compared area under the curve of the receiver operating characteristic (AUC-ROC) of urinary NGAL with that of the urinary NGAL/hepcidin-25 ratio within 60 minutes after end of surgery. We compared adjusted AUC and performed cross-validated reclassification statistics of the (logarithmic) urinary NGAL/hepcidin-25 ratio adjusted to Cleveland risk score/EuroScore, cross-clamp time, age, volume of packed red blood cells, and (logarithmic) urinary NGAL concentration. The association of the NGAL/hepcidin-25 ratio with long-term patient survival was assessed using Cox proportional hazard regression analysis adjusting for EuroScore, aortic cross-clamp time, packed red blood cells and urinary NGAL. Patients with AKI-RRT (n = 13) had 13.7-times higher NGAL and 3.3-times lower hepcidin-25 concentrations resulting in 46.9-times higher NGAL/hepcidin-25 ratio early after surgery compared to patients without AKI-RRT. The NGAL/hepcidin-25 ratio had higher AUC-ROC compared with NGAL for risk of AKI-RRT and in-hospital mortality (unadjusted AUC-ROC difference 0.087, 95% confidence interval [CI], 0.036-0.138, P < .001; 0.082, 95% CI, 0.018-0.146, P = .012). For AKI-RRT, the NGAL/hepcidin-25 ratio increased adjusted category-free net reclassification improvement (cfNRI; 0.952, 95% CI, 0.437-1.468; P < .001) and integrated discrimination improvement (IDI; 0.040, 95% CI, 0.008-0.073; P = .016) but not AUC difference. For in-hospital mortality, the ratio improved AUC of the reference model (AUC difference 0.056, 95% CI, 0.003-0.108; P = .037) and cfNRI but not IDI. The urinary NGAL/hepcidin-25 ratio remained significantly associated with long-term mortality after adjusting for the model covariates. The urinary NGAL/hepcidin-25 ratio appears to early identify high-risk patients and outperform NGAL after cardiac surgery. Confirmation of our findings in other cardiac surgery centers is now needed. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/27592 | DOI: | 10.1213/ANE.0000000000005741 | Journal: | Anesthesia and Analgesia | PubMed URL: | 34543256 | Type: | Journal Article |
Appears in Collections: | Journal articles |
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