The main bottleneck in studies aiming to identify novel
biomarkers in
acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal
ischemia/reperfusion (I/R) model to identify new, predominantly renal
biomarker candidates for
kidney disease. Urine and serum samples were analyzed in pre-
ischemia,
ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion.
Peptides were analyzed on the Q-Exactive™. In renal cortex
proteome, we observed an increase in the synthesis of
proteins in the ischemic kidney compared to the contralateral, highlighted by
transcription factors and epithelial adherens junction
proteins. Intersecting the set of
proteins up- or down-regulated in the ischemic tissue with both serum and urine
proteomes, we identified 6
proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal,
proteins in urine. As prove of concept, we validated one of the identified
biomarkers,
dipeptidyl peptidase IV, in a set of patients with
diabetic nephropathy. In conclusion, we identified 55 systemic
proteins, some of them predominantly renal, candidates for
biomarkers of renal disease.
BIOLOGICAL SIGNIFICANCE: The main bottleneck in studies aiming to identify novel
biomarkers in
acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative
biomarkers for this condition have also been identified in a number of other clinical scenarios, such as
cardiovascular diseases,
chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential
biomarkers for
kidney disease, using kidney
ischemia/reperfusion as a paradigm for a kidney pathological event.