title: Preoperative plasma growth-differentiation factor-15 for prediction of acute kidney injury in patients undergoing cardiac surgery.
abstract: Growth-differentiation factor-15 (GDF-15) is an emerging humoral marker for risk stratification in cardiovascular disease. Cardiac-surgery-associated acute kidney injury (CSA-AKI), an important complication in patients undergoing cardiac surgery, is associated with poor prognosis. The present secondary analysis of an observational cohort study aimed to determine the role of GDF-15 in predicting CSA-AKI compared with the Cleveland-Clinic Acute Renal Failure (CC-ARF) score and a logistic regression model including variables associated with renal dysfunction.
  
  
  
  Preoperative plasma GDF-15 was determined in 1176 consecutive patients undergoing elective cardiac surgery. Patients with chronic kidney disease stage 5 were excluded. AKI was defined according to Kidney-Disease-Improving-Global-Outcomes (KDIGO) - creatinine criteria. The following variables were screened for association with development of postoperative AKI: age, gender, additive Euroscore, serum creatinine, duration of cardiopulmonary bypass, duration of surgery, type of surgery, total circulatory arrest, preoperative hemoglobin, preoperative oxygen-supplemented cerebral oxygen saturation, diabetes mellitus, hemofiltration during ECC, plasma GDF-15, high sensitivity troponin T (hsTNT), and N-terminal prohormone of B-type natriuretic peptide (NTproBNP).
  
  
  
  There were 258 patients (21.9 %) with AKI (AKI stage 1 (AKI-1), n = 175 (14.9 %); AKI-2, n = 6 (0.5 %); AKI-3, n = 77 (6.5 %)). The incidence of AKI-1 and AKI-3 increased significantly from the lowest to the highest tertiles of GDF-15. In logistic regression, preoperative GDF-15, additive Euroscore, age, plasma creatinine, diabetes mellitus, and duration of cardiopulmonary bypass were independently associated with AKI. Inclusion of GDF-15 in a logistic regression model comprising these variables significantly increased the area under the curve (AUC 0.738 without and 0.750 with GDF-15 included) and the net reclassification ability to predict AKI. Comparably, in receiver operating characteristic analysis the predictive capacity of the CC-ARF score (AUC 0.628) was improved by adding GDF-15 (AUC 0.684) but this score also had lower predictability than the logistic regression model. In random forest analyses the predictive capacity of GDF-15 was especially pronounced in patients with normal plasma creatinine.
  
  
  
  This suggests that preoperative plasma GDF-15 independently predicts postoperative AKI in patients undergoing elective cardiac surgery and is particularly helpful for risk stratification in patients with normal creatinine.
  
  
  
  NCT01166360 on July 20, 2010.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Ratzeburger Allee 160, D - 23538, Luebeck, Germany. Heringlake@t-online.de.
authors.forename: Matthias
authors.identifier: 0000-0001-6949-7113
authors.initials: M
authors.lastname: Heringlake
authors.affiliation: Department of Cardiac Surgery, Martin-Luther University, Halle, Germany.
authors.forename: Efstratios I
authors.initials: EI
authors.lastname: Charitos
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Ratzeburger Allee 160, D - 23538, Luebeck, Germany.
authors.forename: Kira
authors.initials: K
authors.lastname: Erber
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Ratzeburger Allee 160, D - 23538, Luebeck, Germany.
authors.forename: Astrid Ellen
authors.initials: AE
authors.lastname: Berggreen
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Ratzeburger Allee 160, D - 23538, Luebeck, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Heinze
authors.affiliation: Department of Cardiac Anesthesiology, HELIOS - Clinic, Schwerin, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Paarmann
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology / Q000209:etiology*; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects* / Q000706:statistics & numerical data; D015331:Cohort Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000032:analysis* / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology; D011379:Prognosis; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: Acute kidney injury; Biomarkers; Cardiac surgery; Cleveland Clinic Acute Renal Failure score; Euroscore; Growth-differentiation factor-15