Neutrophil Gelatinase-Associated Lipocalin (NGAL) As An Early Predictor Of Acute Kidney Injury Following Cardiopulmonary Bypass Supported Cardiac Surgery
| dc.contributor.advisor | McNair, Erick | |
| dc.contributor.committeeMember | Magee, Fergall | |
| dc.contributor.committeeMember | Harding, Sheila | |
| dc.contributor.committeeMember | Fonge, Humphrey | |
| dc.creator | Bezaire, Jennifer Lynn | |
| dc.creator.orcid | 0000-0001-9039-6384 | |
| dc.date.accessioned | 2023-09-20T14:32:40Z | |
| dc.date.available | 2023-09-20T14:32:40Z | |
| dc.date.copyright | 2023 | |
| dc.date.created | 2023-08 | |
| dc.date.issued | 2023-09-20 | |
| dc.date.submitted | August 2023 | |
| dc.date.updated | 2023-09-20T14:32:40Z | |
| dc.description.abstract | Background Cardiac surgery-associated acute kidney injury (CSA-AKI) increases morbidity and mortality and is an adverse outcome in patients undergoing cardiopulmonary bypass supported cardiac surgical procedures. A lack of consensus in the literature on the definition of AKI and identification of effective diagnostic criteria are factors associated with delayed diagnosis. Diagnostic delay leads to intervention and treatment delays, increasing the risk of adverse outcomes. Tubular injury precedes a significant rise in SCr, yet clinicians still use SCr and eGFR to evaluate renal function, thus delaying early treatment of AKI. SCr is not an early indicator of AKI due to its slow rise and poor predictive accuracy for renal injury. Further, SCr demonstrates poor sensitivity for the early diagnosis of AKI and cannot differentiate between the various causes of AKI (Bonventre, 2007). SCr is a suboptimal biomarker of AKI due to its delayed measure of changes in renal function, hampered by dilutional effects of intravenous fluid administration (Macedo et al., 2010) and decreased creatinine production (Pickering et al., 2013). The widely accepted use of SCr monitoring cannot facilitate early detection and treatment of AKI. Hence, this study aims to investigate serial measures of urine and serum NGAL concentrations as predictive and diagnostic biomarkers of CSA-AKI. Methods This research was a prospective study of 334 CPB-supported adult cardiac surgery patients. Thirty patients developed CSA-AKI (Group I) according to the 2020 KDIGO AKI classification (Ostermann et al., 2020). From the remaining 204 non-CSA-AKI patients, a matched design was used to select a sample of 30 patients (Group II) matched with the Group I patients by age (± 10 years), gender, BMI (± 5kg/m2), EuroScore (± 10), pre-CPB eGFR (± 5 ml/min/1.73 m2) and type of surgery, rendering a final sample of 60 patients. Demographic data and clinical characteristics were collected pre-operatively, intra-operatively, and five days post-operatively. Urine and serum specimens for NGAL measurements were obtained at pre-CPB (before surgery), 10 min post-CPB, and 4 hr post-CPB. Urine and serum NGAL were measured via ELISA. SCr was measured pre-CPB, 2 hr, 8 hr, and 18 hr post-CPB and each day thereafter until discharge using the standard in-hospital laboratory analyzer. Results This study demonstrated that the mean time to CSA-AKI diagnosis based on KDIGO (2020) criteria was 36 hr in the AKI group. The pre-procedural levels of urine and serum NGAL in this cohort were not predictive of CSA-AKI. Both urine and serum NGAL 10 min and 2 hr post-CPB detected CSA-AKI sooner than the gold standard SCr and eGFR. Serum NGAL measured 10 min post-CPB demonstrated the best performance as a predictor of CSA-AKI as compared to urine NGAL at all time points, with AUC = 0.8767 (95% CI 0.78311 – 0.97022). The impact of component transfusion, other than RBCs, on CSA-AKI remains virtually unexplored. The results of the present study also support the observation (Rasmussen et al., 2020) that intraoperative transfusion of blood products including RBC, platelets, and FFP increases the likelihood of developing CSA-AKI. Conclusion This research study demonstrates that rising serum and urine levels of NGAL are associated with the clinical endpoint of CSA-AKI. Furthermore, this study also demonstrates that blood component transfusion is associated with increased risk for CSA-AKI. In addition, both serum and urine NGAL levels appear to rise earlier as compared to standard SCr measurement and eGFR calculation. Both serum and urine NGAL are CSA-AKI indicators, that enable early post-operative identification of patients who develop CSA-AKI. Serum NGAL 10 min post-CPB proved to be an independent predictor of developing CSA-AKI prior to changes in SCr and eGFR. The odds ratio for developing CSA-AKI based on sNGAL ≥ 7000 pg/ml 10 min post-CPB is 1.544 (95% CI 1.234, 1.931). This suggests that those with a positive sNGAL 10 min post-CPB are 1.5 times more likely to develop AKI. NGAL kidney injury biomarkers are an eligible early diagnostic tool for CSA-AKI as soon as 10 min post-CPB. This study suggests that sNGAL is a viable renal biomarker that could potentially be used to both monitor renal perfusion and function intraoperatively and optimize peri-operative care in cardiac surgical patients. Thus, NGAL testing may be an option for earlier intervention in this patient population. Earlier intervention could improve outcomes, mortality, and overall cost of delivery of care. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/15016 | |
| dc.language.iso | en | |
| dc.subject | acute kidney injury | |
| dc.subject | cardiopulmonary bypass | |
| dc.subject | neutrophil gelatinase-associated lipocalin | |
| dc.subject | NGAL | |
| dc.title | Neutrophil Gelatinase-Associated Lipocalin (NGAL) As An Early Predictor Of Acute Kidney Injury Following Cardiopulmonary Bypass Supported Cardiac Surgery | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Medicine | |
| thesis.degree.discipline | Health Sciences | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |