Abstract 1920: Aprotinin Increases the Risk of Acute Kidney Injury Following Pediatric Cardiac Surgery
Background: Acute kidney injury (AKI) is a common cause of morbidity and mortality in hospitalized patients, affecting up to 30% of patients undergoing cardiopulmonary bypass (CPB). Serum creatinine (SCr), the current standard, is an inadequate marker for AKI since a delay occurs before a rise in SCr occurs. Biomarkers that are sensitive and rapidly measurable could improve patient outcomes. Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELD-TOF-MS) for proteomic profiling in urine from children undergoing CPB, we identified 4 peaks that predict AKI after CPB. We previously identified 3 of the biomarkers as α1-microglobulin, α1-acid-glycoprotein and albumin. For the present study, we sought to identify and characterize the candidate urinary biomarker with a mass-to-charge ratio of 6.5kDa.
Methods: Children undergoing CPB were prospectively enrolled, and clinical data with urine samples were collected before CPB (t=0) and 2h after start of CPB (t=2). Patients with known renal disease or receiving nephrotoxic drugs were excluded. Trypsin-digested bands isolated by gel electrophoresis were analyzed by tandem MS/MS to identify the protein. An amidolytic assay measuring functional activity and SELDI-TOF-MS analysis were performed to quantify protein levels. AKI was defined as a >50% rise in SCr from baseline.
Results: The 6.5kDa protein was identified as bovine aprotinin, an antifibrinolytic given to reduce blood loss. In our prospective cohort of 106 patients, aprotinin was used in 50% and its use was associated with a 5-fold increase in the incidence of AKI (9.4% vs 51%, p<0.0001) with an odds ratio of 8.5 (CI 2.6–27.8, p= 0.004). Urinary aprotinin levels 2h after CPB measured by an amidolytic substrate assay predicted AKI with 92% sensitivity and 96% specificity. Peak intensities determined by SELDI-TOF-MS corroborate this finding. Using multivariate regression analysis, urinary aprotinin levels 2h after CPB were the most powerful independent predictor of AKI in these patients.
Conclusion: Administration of aprotinin is associated with a significantly increased risk of developing AKI after CPB. Urinary aprotinin levels measured at 2h post-CPB are predictive of AKI in pediatric patients undergoing CPB.