Rady Faculty of Health Sciences

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Browsing Rady Faculty of Health Sciences by Subject "acute kidney injury"

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    Activity-based protein profiling of intraoperative serine hydrolase activities during cardiac surgery
    (American Chemical Society Publications, 2018-09-07) Navarette, Mario; Ho, Julie; Dwivedi, Ravi; Choi, Nora; Ezzati, Peyman; Krokhin, Oleg; Spicer, Vic; Arora, Rakesh; Rigatto, Claudio; Wilkins, John
    The processes involved in the initiation of acute kidney injury (AKI) following cardiopulmonary bypass (CPB) are thought to occur during the intraoperative period. Such a rapid development might indicate that some of the inductive events are not dependent on de novo protein synthesis, raising the possibility that changes in activities of pre-existing enzymes could contribute to the development of AKI. Activity-based protein profiling (ABPP) was used to compare the serine hydrolase enzyme activities present in the urines of CPB patients who subsequently developed AKI versus those who did not (non-AKI) during the intra- and immediate postoperative periods. Sequential urines collected from a nested case-control cohort of AKI and non-AKI patients were reacted with a serine hydrolase activity probe, fluorophosphonate-TAMRA, and separated by SDS-PAGE. The patterns and levels of probe-labeled proteins in the two groups were initially comparable. However, within 1 h of CPB there were significant pattern changes in the AKI group. Affinity purification and mass spectrometry-based analysis of probe-labeled enzymes in AKI urines at 1 h CPB and arrival to the intensive care unit (ICU) identified 28 enzymes. Quantitative analysis of the activity of one of the identified enzymes, kallikrein-1, revealed some trends suggesting differences in the levels and temporal patterns of enzyme activity between a subset of patients who developed AKI and those who did not. A comparative analysis of affinity-purified probe reacted urinary proteins from these patient groups during the intraoperative period suggested the presence of both shared and unique enzyme patterns. These results indicate that there are intraoperative changes in the levels and types of serine hydrolase activities in patients who subsequently develop AKI. However, the role of these activity differences in the development of AKI remains to be determined.
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    Intraoperative prediction of cardiac surgery-associated acute kidney injury
    (2015-08-07) Crosina, Jordan
    Cardiac surgery associated acute kidney injury (CSA-AKI) is a potentially lethal complication which occurs in up to 30% of cardiac surgery patients. When the injury is severe enough to necessitate dialysis (which occurs in approximately 1% to 2% of patients) it confers a 19-fold increase in the odds of death. Even when the injury is relatively modest (i.e. a 25 % rise in postoperative serum creatinine), it is independently associated with morbidity and mortality. A major barrier to preventing CSA-AKI is the lack of available strategies for early detection of kidney injury. Work done by our team has established Hepcidin-25 as a novel urine biomarker of CSA-AKI. Newer data suggest NGAL, OSMR, MMP-2, and Klotho are also potential early biomarkers of CSAAKI. Objective: To study the value of 5 urine and serum biomarkers in the diagnosis of incipient CSA-AKI. A unique and novel aspect of our project will be assessing the value of intraoperative measurements of these biomarkers. Design: Prospective cohort study of 350 cardiac surgery patients (280 patients have already been recruited)