Proteomic identification of early biomarkers of acute kidney injury after cardiac surgery in children.
BACKGROUND
Serum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery.


METHODS
Diagnostic test study.


METHODS
Children undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year).


METHODS
Biomarkers identified using proteomic profiling: α(1)-microglobulin, α(1)-acid glycoprotein, and albumin.


METHODS
AKI, defined as ≥50% increase in serum creatinine level from baseline within 3 days of surgery.


RESULTS
Proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as α(1)-microglobulin, α(1)-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001).


CONCLUSIONS
Single-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range.


CONCLUSIONS
Urinary α(1)-microglobulin, α(1)-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery.
Devarajan
Prasad
P
Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, 45229-3039, USA. prasad.devarajan@cchmc.org
Krawczeski
Catherine D
CD
Nguyen
Mai T
MT
Kathman
Thelma
T
Wang
Zhu
Z
Parikh
Chirag R
CR
D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology; D000209:Acute-Phase Proteins / Q000652:urine*; D000510:Alpha-Globulins / Q000652:urine*; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000175:diagnosis / Q000453:epidemiology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D015415:Biomarkers; C016001:alpha-1-microglobulin; D003404:Creatinine