Open Access Research

Urinary proteomic shotgun approach for identification of potential acute rejection biomarkers in renal transplant recipients

Håvard Loftheim1,2, Karsten Midtvedt3, Anders Hartmann3, Anna V Reisæter3, Pål Falck2, Hallvard Holdaas3, Trond Jenssen3, Leon Reubsaet1 and Anders Åsberg2*

Author Affiliations

1 Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O.Box. 1068, Blindern, NO-0316, Oslo, Norway

2 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway

3 Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Norway

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Transplantation Research 2012, 1:9 doi:10.1186/2047-1440-1-9

Published: 31 August 2012

Abstract

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).

Conclusion

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.

Trial registration

ClinicalTrials.gov number NCT00139009

Keywords:
Acute rejection; Biomarker; Renal transplantation; Urinary proteomics