Association between peritransplant kidney injury biomarkers and 1-year allograft outcomes.
OBJECTIVE
Current tools to predict outcomes after kidney transplantation are inadequate. The objective of this study was to determine the association of perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 with poor 1-year allograft function (return to dialysis or estimated GFR<30 ml/min per 1.73 m(2)).


METHODS
Neutrophil gelatinase-associated lipocalin and IL-18 from early post-transplant urine was measured in this prospective, multicenter study of deceased-donor kidney transplant recipients. The outcome of poor allograft function at 1 year relative to these biomarkers using multivariable logistic regression and net reclassification improvement was examined. Also, the interaction between delayed graft function and the biomarkers on the outcome were evaluated, and the change in biomarkers over consecutive days related to the outcome using trend tests was examined.


RESULTS
Mean age for the 153 recipients was 54 ± 13 years. Delayed graft function occurred in 42%, and 24 (16%) recipients had the 1-year outcome. Upper median values for neutrophil gelatinase-associated lipocalin and IL-18 on the first postoperative day had adjusted odds ratios (95% confidence interval) of 6.0 (1.5-24.0) and 5.5 (1.4-21.5), respectively. Net reclassification improvement (95% confidence interval) was significant for neutrophil gelatinase-associated lipocalin and IL-18 at 36% (1%-71%) and 45% (8%-83%), respectively. There was no significant interaction between biomarkers and delayed graft function on the outcome. Change in biomarkers moderately trended with the outcome.


CONCLUSIONS
Perioperative urine neutrophil gelatinase-associated lipocalin and IL-18 are associated with poor 1-year allograft function, suggesting their potential for identifying patients for therapies that minimize the risk of additional injury.
Program of Applied Translational Research, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Isaac E
IE
Hall
Mona D
MD
Doshi
Peter P
PP
Reese
Richard J
RJ
Marcus
Heather
H
Thiessen-Philbrook
Chirag R
CR
Parikh
D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D051799:Delayed Graft Function / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000652:urine*; D006801:Humans; D020382:Interleukin-18 / Q000652:urine*; D016030:Kidney Transplantation / Q000009:adverse effects*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000652:urine*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000209:Acute-Phase Proteins; D015415:Biomarkers; D020382:Interleukin-18; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins