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. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 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). INDEX TESTS: Biomarkers identified using proteomic profiling: α(1)-microglobulin, α(1)-acid glycoprotein, and albumin. REFERENCE TEST: 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). LIMITATIONS: 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.
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. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 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). INDEX TESTS: Biomarkers identified using proteomic profiling: α(1)-microglobulin, α(1)-acid glycoprotein, and albumin. REFERENCE TEST: 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). LIMITATIONS: 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.
Authors: C M Mangano; L S Diamondstone; J G Ramsay; A Aggarwal; A Herskowitz; D T Mangano Journal: Ann Intern Med Date: 1998-02-01 Impact factor: 25.391
Authors: Stefan Herget-Rosenthal; Dennis Poppen; Johannes Hüsing; Günter Marggraf; Frank Pietruck; Heinz-Günther Jakob; Thomas Philipp; Andreas Kribben Journal: Clin Chem Date: 2004-01-06 Impact factor: 8.327
Authors: Andrea Lassnigg; Daniel Schmidlin; Mohamed Mouhieddine; Lucas M Bachmann; Wilfred Druml; Peter Bauer; Michael Hiesmayr Journal: J Am Soc Nephrol Date: 2004-06 Impact factor: 10.121
Authors: Raj Munshi; Ali Johnson; Edward D Siew; T Alp Ikizler; Lorraine B Ware; Mark M Wurfel; Jonathan Himmelfarb; Richard A Zager Journal: J Am Soc Nephrol Date: 2010-11-11 Impact factor: 10.121
Authors: Markus Berger; Lucélia Santi; Walter O Beys-da-Silva; Fabrício Marcus Silva Oliveira; Marcelo Vidigal Caliari; John R Yates; Maria Aparecida Ribeiro Vieira; Jorge Almeida Guimarães Journal: Arch Toxicol Date: 2014-05-06 Impact factor: 5.153
Authors: Mina H Hanna; Alessandra Dalla Gassa; Gert Mayer; Gianluigi Zaza; Patrick D Brophy; Loreto Gesualdo; Francesco Pesce Journal: Pediatr Nephrol Date: 2016-03-09 Impact factor: 3.714
Authors: Emily M Bucholz; Richard P Whitlock; Michael Zappitelli; Prasad Devarajan; John Eikelboom; Amit X Garg; Heather Thiessen Philbrook; Philip J Devereaux; Catherine D Krawczeski; Peter Kavsak; Colleen Shortt; Chirag R Parikh Journal: Pediatrics Date: 2015-03-09 Impact factor: 7.124
Authors: Michael Zappitelli; Steven G Coca; Amit X Garg; Catherine D Krawczeski; Philbrook Thiessen Heather; Kyaw Sint; Simon Li; Chirag R Parikh; Prasad Devarajan Journal: Clin J Am Soc Nephrol Date: 2012-08-23 Impact factor: 8.237