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This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007101137v1 20/2/428    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quintana, L. F. Articles by Campistol, J. M. Search for Related Content PubMed PubMed Citation Articles by Quintana, L. F. Articles by Campistol, J. M. Related Collections Related Article

Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

Luís F. Quintana^*,, Amanda Solé-Gonzalez, Susana G. Kalko, Elisenda Bañon-Maneus, Manel Solé, Fritz Diekmann^,||, Alex Gutierrez-Dalmau, Joaquin Abian^¶ and Josep M. Campistol^*,

^* Servicio de Nefrología y Trasplante renal, Laboratorio Experimental de Nefrología y Trasplante renal, Unidad de Bioinformática, Servicio Anatomía Patologica, Hospital Clinic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, and ^¶ Laboratorio de Proteómica Consejo Superior de Investigaciones Científicas (CSIC)/Universidad Autonoma, Instituto de Investigaciones Biomedicas de Barcelona/CSIC-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; and ^|| Department of Nephrology, Charité Campus Mitte, Berlin, Germany

Correspondence: Dr. Luís F. Quintana, Servicio de Nefrología y Trasplante renal, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Phone and Fax: 34-3-2275444; E-mail: lfquinta{at}clinic.ub.es

Received for publication October 23, 2007. Accepted for publication August 27, 2008.

Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction.

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Peter Nickerson and Peter S. Heeger
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This article has been cited by other articles:

				L. F. Quintana, J. M. Campistol, M. P. Alcolea, E. Banon-Maneus, A. Sol-Gonzalez, and P. R. Cutillas Application of Label-free Quantitative Peptidomics for the Identification of Urinary Biomarkers of Kidney Chronic Allograft Dysfunction Mol. Cell. Proteomics, July 1, 2009; 8(7): 1658 - 1673. [Abstract] [Full Text] [PDF]

				P. Nickerson and P. S. Heeger Proteomic Portrayal of Transplant Pathologies J. Am. Soc. Nephrol., February 1, 2009; 20(2): 236 - 238. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673