Perioperative management
Urinary proteomics before and after extracorporeal circulation in patients with and without acute kidney injury

https://doi.org/10.1016/j.jtcvs.2009.11.015Get rights and content
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Objective

Acute kidney injury is a well-known complication with high morbidity and mortality after cardiopulmonary bypass. Cardiopulmonary bypass–associated acute kidney injury is still poorly understood.

Methods

Thirty-six patients undergoing elective cardiopulmonary bypass were enrolled. Spot urine samples before and after cardiopulmonary bypass were collected. Acute kidney injury was defined according to the RIFLE classification. To identify differentially regulated proteins after cardiopulmonary bypass, we first analyzed the urinary proteome before and after cardiopulmonary bypass. To identify differentially regulated proteins in acute kidney injury, we next compared the urinary proteome obtained on the first postoperative day between patients with and without acute kidney injury. Difference fluorescence gel electrophoresis was used to compare protein profiles and mass spectrometry to identify individual proteins.

Results

After cardiopulmonary bypass, inflammation-associated (zinc-alpha-2-glycoprotein, leucine-rich alpha-2-glycoprotein, mannan-binding lectin serine protease 2, basement membrane-specific heparan sulfate proteoglycan, and immunoglobulin kappa) or tubular dysfunction-associated (retinol-binding protein, adrenomedullin-binding protein, and uromodulin) proteins were differentially regulated. Acute kidney injury developed in 6 of 36 patients. A modified urinary albumin was increased, and zinc-alpha-2-glycoprotein and a fragment of adrenomedullin-binding protein were decreased in patients with acute kidney injury. Decreased excretion of zinc-alpha-2-glycoprotein in patients with acute kidney injury was confirmed by Western blot and enzyme-linked immunosorbent assay in an independent cohort of 22 patients with and 46 patients without acute kidney injury.

Conclusion

Cardiopulmonary bypass leads to increased urinary excretion of inflammatory proteins and markers of tubular injury. Zinc-alpha-2-glycoprotein is a potentially useful predictive marker for acute kidney injury after cardiopulmonary bypass surgery.

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Abbreviations and Acronyms

2D
2-dimensional
AKI
acute kidney injury
AMBP
adrenomedullin-binding protein
AUC
area under the curve
CPB
cardiopulmonary bypass
DIGE
difference gel electrophoresis
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
GFR
glomerular filtration rate
HSPG
heparan sulfate proteoglycan
MALDI-MS
matrix-assisted laser desorption ionization time-of-flight mass spectrometry
MALDI-MS/MS
matrix-assisted laser desorption ionization time-of-flight mass spectrometry/mass spectrometry
NGAL
neutrophil gelatinase-associated lipocalin
RBP
retinol-binding protein
SELDI-TOF-MS
surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
SIRS
systemic inflammatory response syndrome
ZAG
zinc-alpha-2-glycoprotein

Cited by (0)

Grant support: Swiss National Foundation for Scientific Research Number 3100A0-102153 to F.J.F. and B.M.F.

Disclosures: None.

F.A. and C.P. contributed equally to the article.