Advisory Committee Chair
Alexander J Szalai
Advisory Committee Members
Anupam Agarwal
Chad Steele
Hubert M Tse
Scott R Barnum
Document Type
Dissertation
Date of Award
2015
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. Characteristically during inflammation there is an increase in the blood level of Creactive protein (CRP), an acute phase reactant whose rise associates with worsened outcomes of AKI. Despite this association, no studies have previously investigated whether CRP has an active role in the AKI process. Using transgenic mice that express human CRP, wild type mice, and CRP-deficient mice (CRP-/-) we show here that CRP can exacerbate renal damage as early as 24 hours after injury. While many types of immune cells have been implicated in the damaging inflammatory response in AKI, we provide evidence that myeloid derived suppressor cells are likely the CRP responsive leukocyte of importance in AKI. Our data showing that CRP modifies pathways of importance regulating the inflammatory cell response could lead to more effective therapeutic options for AKI.
Recommended Citation
Pegues, Melissa A., "The role of C-reactive protein in acute kidney injury" (2015). All ETDs from UAB. 2694.
https://digitalcommons.library.uab.edu/etd-collection/2694
