Identifying candidate protein markers of acute kidney injury in acute decompensated heart failure using sheep kidney cortex

ABSTRACT: A quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI), an abrupt loss of kidney function that doubles the risk of death at one-year. There is a critical need to identify early markers for AKI in ADHF, however, no protein candidates have been validated as diagnostic or prognostic biomarkers in this setting. We aimed to identify novel candidate protein biomarkers by quantifying changes in protein expression in the kidney that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using Sequential Window Acquisition of All Theoretical Mass Spectrometry (SWATH-MS) in kidney cortex from healthy control sheep (n=5), sheep with established rapid pacing-induced ADHF (n=8) and sheep after ~4 weeks recovery from ADHF (n=7). Of 790 proteins quantified, we identified 17 candidate kidney injury markers, one potential marker of kidney recovery and two markers of long-term renal impairment that were differentially expressed between groups (1.2-2.6 fold-change, p<0.05). Differentially expressed proteins were enriched in pro-inflammatory signaling pathways: Glycoprotein VI (activated during ADHF development, adjusted p<0.01) and acute phase response (repressed during recovery from ADHF, p<0.01). This research identified 20 candidate protein markers of kidney injury, including 6 promising candidates supported by existing evidence and 14 novel candidates never implicated in AKI. Early awareness of AKI in ADHF through the use of biomarkers has the potential to reduce mortality and improve outcomes for these at-risk patients.

INSTRUMENT(S): TripleTOF 5600+

ORGANISM(S): Ovis Aries

TISSUE(S): Kidney

DISEASE(S): Congestive Heart Failure

SUBMITTER: Evie Templeton  

LAB HEAD: Victoria Anne Cameron

PROVIDER: PXD028983 | Pride | 2022-01-19

REPOSITORIES: Pride