Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients.
BACKGROUND
Acute rejection (AR) episodes in renal transplant recipients are suspected when plasma creatinine is elevated and other potential causes out ruled. Graft biopsies are however needed for definite diagnosis. Non-invasive AR-biomarkers is an unmet clinical need. The urinary proteome is an interesting source in the search for such a biomarker in this population.


METHODS
In this proof of principle study, serial urine samples in the early post transplant phase from 6 patients with biopsy verified acute rejections and 6 age-matched controls without clinical signs of rejection were analyzed by shotgun proteomics.


RESULTS
Eleven proteins fulfilled predefined criteria for regulation in association with AR. They presented detectable regulation already several days before clinical suspicion of AR (increased plasma creatinine). The regulated proteins could be grouped by their biological function; proteins related to growth and proteins related to immune response. Growth-related proteins (IGFBP7, Vasorin, EGF and Galectin-3-binding protein) were significantly up-regulated in association with AR (P = 0.03) while proteins related to immune response (MASP2, C3, CD59, Ceruloplasmin, PiGR and CD74) tended to be up-regulated ( P = 0.13).


CONCLUSIONS
The use of shotgun proteomics provides a robust and sensitive method for identification of potentially predictive urinary biomarkers of AR. Further validation of the current findings is needed to establish their potential clinical role with regards to clinical AR diagnosis.


BACKGROUND
ClinicalTrials.gov number NCT00139009.
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. anders.asberg@farmasi.uio.no.
Håvard
H
Loftheim
Karsten
K
Midtvedt
Anders
A
Hartmann
Anna V
AV
Reisæter
Pål
P
Falck
Hallvard
H
Holdaas
Trond
T
Jenssen
Leon
L
Reubsaet
Anders
A
Asberg