title: A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde.
abstract: BACKGROUND
  Serum creatinine (SCr) alone does not allow for the early diagnosis of delayed graft function (DGF) following kidney transplantation (KTx).
  
  
  OBJECTIVE
  The diagnostic utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum leptin, malondialdehyde (MD.A), and cystatin C (CysC) for the early detection of DGF was previously evaluated by our group in a prospective cohort study of 40 consecutive adults undergoing KTx. Because no single biomarker achieved adequate sensitivity or specificity for practical purposes, this study was designed to evaluate the combined use of new markers with SCr. Urine and blood samples were collected 8-to-12h after KTx (day-1). Logistic regression was used to combine the biomarkers, and receiver operating characteristic curves and areas under the curve (AUC-ROC) were generated.
  
  
  RESULTS
  Eighteen recipients developed DGF (dialysis requirement during the first post-transplant week). On day-1, the AUC for SCr to predict DGF was 0.73, 0.88 for uNGAL, 0.90 for MDA, 0.76 for leptin, and 0.91 for CysC. Adding new biomarkers to SCr enhanced the performance of DGF prediction, and the best combination was achieved with SCr, MDA, and CysC (AUC=0.96, sensitivity=100%; specificity=86%).
  
  
  CONCLUSIONS
  A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC.
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal; EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal. Electronic address: isabelf27@gmail.com.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fonseca
authors.affiliation: Department of Clinical Chemistry, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
authors.forename: Henrique
authors.initials: H
authors.lastname: Reguengo
authors.affiliation: Department of Clinical Chemistry, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Oliveira
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: La Salete
authors.initials: LS
authors.lastname: Martins
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Malheiro
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Josefina
authors.initials: J
authors.lastname: Santos
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
authors.forename: Leonídio
authors.initials: L
authors.lastname: Dias
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pedroso
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: Luísa
authors.initials: L
authors.lastname: Lobato
authors.affiliation: Department of Nephrology and Kidney Transplantation, Centro Hospitalar do Porto, Hospital de Santo António, Porto, Portugal; Unit for Multidisciplinary Investigation in Biomedicine (UMIB), Porto, Portugal.
authors.forename: António Castro
authors.initials: AC
authors.lastname: Henriques
authors.affiliation: EPIUnit - Institute of Public Health, University of Porto, Porto, Portugal; Department of Population Studies, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Denisa
authors.initials: D
authors.lastname: Mendonça
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology / Q000601:surgery; D007677:Kidney Function Tests / Q000379:methods; D016030:Kidney Transplantation / Q000379:methods; D020738:Leptin / Q000097:blood; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine; D012372:ROC Curve; D006435:Renal Dialysis / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D055316:Cystatin C; C489506:LCN2 protein, human; D020738:Leptin; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D008315:Malondialdehyde; D003404:Creatinine
keywords: Biomarkers; Cystatin C; Delayed graft function; Kidney transplantation; Malondialdehyde