Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation. 1. Introduction Overt proteinuria is an established prognostic marker in renal allograft recipients associated with allograft dysfunction and graft loss [1, 2]. However, the early detection of the causes of graft dysfunction and graft loss is important. The current modality for definitive diagnosis of graft abnormalities is graft biopsy [3]. Inherent risk of biopsy on a single transplanted kidney and delay involved in the detailed reporting of the tissue could preclude an early diagnosis of the graft dysfunction and early institution of specific therapy. On the other hand, urinary proteome is a distinct entity from the conventional nosology of proteinuria that has been emerging in recent years [4, 5]. Urinary proteome constitutes the entire genomic protein content that is excreted in urine in health and disease states. Proteomic urine analysis could predict the diagnosis of renal transplant pathologies early, which could impact the graft function and survival in the long run [5]. Moreover, urinary proteome patterns in transplant patients could differentiate stable graft function from acute tubulointerstitial rejection (AR), urinary tract infection (UTI), acute tubular necrosis (ATN), and calcineurin inhibitor (CNI) toxicity [6]. In addition, characterization of chronic allograft dysfunction into chronic antibody associated rejection (CAAR), interstitial fibrosis tubular atrophy
References
[1]
M. K. Shamseddin and G. A. Knoll, “Posttransplantation proteinuria: an approach to diagnosis and management,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 7, pp. 1786–1793, 2011.
[2]
S. M. Suhail, T. S. Y. Kee, K. T. Woo et al., “Impact of patterns of proteinuria on renal allograft function and survival: a prospective cohort study,” Clinical Transplantation, vol. 25, no. 3, pp. E297–E303, 2011.
[3]
L. C. Racusen, K. Solez, R. B. Colvin et al., “The Banff 97 working classification of renal allograft pathology,” Kidney International, vol. 55, no. 2, pp. 713–723, 1999.
[4]
B. A. Julian, H. Suzuki, Y. Suzuki, Y. Tomino, G. Spasovski, and J. Novak, “Sources of urinary proteins and their analysis by urinary proteomics for the detection of biomarkers of disease,” Proteomics, vol. 3, no. 9, pp. 1029–1043, 2009.
[5]
P. Nickerson and P. S. Heeger, “Proteomic portrayal of transplant pathologies,” Journal of the American Society of Nephrology, vol. 20, no. 2, pp. 236–238, 2009.
[6]
S. Wittkea, M. Haubitzb, M. Waldena, et al., “Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients,” The American Journal of Transplantation, vol. 5, pp. 2479–2488, 2005.
[7]
L. F. Quintana, A. Solé-Gonzalez, S. G. Kalko et al., “Urine proteomics to detect biomarkers for chronic allograft dysfunction,” Journal of the American Society of Nephrology, vol. 20, no. 2, pp. 428–435, 2009.
[8]
S. Schaub, D. Rush, J. Wilkins et al., “Proteomic-based detection of urine proteins associated with acute renal allograft rejection,” Journal of the American Society of Nephrology, vol. 15, no. 1, pp. 219–227, 2004.
M. Myslak, H. Amer, P. Morales et al., “Interpreting post-transplant proteinuria in patients with proteinuria pre-transplant,” The American Journal of Transplantation, vol. 6, no. 7, pp. 1660–1665, 2006.
[12]
G. Fernández-Fresnedo, J. J. Plaza, J. Sánchez-Plumed, A. Sanz-Guajardo, R. Palomar-Fontanet, and M. Arias, “Proteinuria: a new marker of long-term graft and patient survival in kidney transplantation,” Nephrology Dialysis Transplantation, vol. 19, no. 3, pp. iii47–iii51, 2004.
[13]
M. T. Pires, A. Santinho da Cunha, G. Virella, and J. Simoes, “Analytical characterization of urinary proteins by sodium dodecyl sulphate polyacrylamide gel electrophoresis in renal disease: clinical and histopathological correlations,” Nephron, vol. 14, no. 5, pp. 361–372, 1975.
[14]
C. Donadio, R. Puccini, A. Lucchesi, R. Giordani, and G. Rizzo, “Urinary excretion of proteins and tubular enzymes in renal transplant patients,” Renal Failure, vol. 20, no. 5, pp. 707–715, 1998.
[15]
J. Fotheringham, C. A. Angel, and W. McKane, “Transplant glomerulopathy: morphology, associations and mechanism,” Nephron, vol. 113, no. 1, pp. c1–c7, 2009.
[16]
P. Hribova, J. Lacha, K. Kotsch et al., “Intrarenal cytokine and chemokine gene expression and kidney graft outcome,” Kidney and Blood Pressure Research, vol. 30, no. 5, pp. 273–282, 2007.
[17]
H. Mischak, C. Delles, J. Klein, and J. P. Schanstra, “Urinary proteomics based on capillary electrophoresis-coupled mass spectrometry in kidney disease: discovery and validation of biomarkers, and clinical application,” Advances in Chronic Kidney Disease, vol. 17, no. 6, pp. 493–506, 2010.
[18]
H. Dihazi and G. A. Müller, “Urinary proteomics: a tool to discover biomarkers of kidney diseases,” Expert Review of Proteomics, vol. 4, no. 1, pp. 39–50, 2007.
[19]
G. H. Tesch, “Review: serum and urine biomarkers of kidney disease: a pathophysiological perspective,” Nephrology, vol. 15, no. 6, pp. 609–616, 2010.
[20]
T. Yamamoto, R. G. Langham, P. Ronco, M. A. Knepper, and V. Thongboonkerd, “Towards standard protocols and guidelines for urine proteomics: a report on the Human Kidney and Urine Proteome Project (HKUPP),” Proteomics, vol. 8, no. 11, pp. 2156–2159, 2008.
[21]
J. F. Timms and R. Cramer, “Difference gel electrophoresis,” Proteomics, vol. 8, no. 23-24, pp. 4886–4897, 2008.
[22]
P. L. Ross, Y. N. Huang, J. N. Marchese et al., “Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents,” Molecular and Cellular Proteomics, vol. 3, no. 12, pp. 1154–1169, 2004.
[23]
P. Meleady, “2D gel electrophoresis and mass spectrometry identification and analysis of proteins,” Methods in Molecular Biology, vol. 784, pp. 123–137, 2011.
[24]
C. Spahr, M. Davis, M. D. McGinley et al., “Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry I: profiling an unfractionated tryptic digest,” Proteomics, vol. 1, no. 1, pp. 93–107, 2001.
[25]
S. K. Akkina, Y. Zhang, G. L. Nelsestuen, W. S. Oetting, and H. N. Ibrahim, “Temporal stability of the urinary proteome after kidney transplant: more sensitive than protein composition?” Journal of Proteome Research, vol. 8, no. 1, pp. 94–103, 2009.
[26]
L. F. Quintana, E. Ba？on-Maneus, A. Solé-Gonzalez, and J. M. Campistol, “Urine proteomics biomarkers in renal transplantation: an overview,” Transplantation, vol. 88, no. 3, pp. S45–S49, 2009.
[27]
Y. Dai, T. Lv, K. Wang, Y. Huang, D. Li, and J. Liu, “Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation,” Saudi Journal of Kidney Diseases and Transplantation, vol. 19, no. 6, pp. 952–959, 2008.
[28]
E. O'Riordan, T. N. Orlova, M. J. Jianfeng et al., “Bioinformatic analysis of the urine proteome of acute allograft rejection,” Journal of the American Society of Nephrology, vol. 15, no. 12, pp. 3240–3248, 2004.
[29]
D. Prasad, “Novel biomarkers for the early prediction of acute kidney injury,” Cancer Therapy, vol. 3, pp. 477–488, 2005.
[30]
K. Bramham, H. D. Mistry, L. Poston, L. C. Chappell, and A. J. Thompson, “The non-invasive biopsy: will urinary proteomics make the renal tissue biopsy redundant?” QJM, vol. 102, no. 8, pp. 523–538, 2009.
[31]
F. Lamoureux, L. N. Gastinel, E. Mestre, P. Marquet, and M. Essig, “Mapping cyclosporine-induced changes in protein secretion by renal cells using stable isotope labeling with amino acids in cell culture (SILAC),” Journal of Proteomics, vol. 27, pp. 3674–3687, 2012.
[32]
S. O'Connell, C. Slattery, M. P. Ryan, and T. McMorrow, “Identification of novel indicators of cyclosporine A nephrotoxicity in a CD-1 mouse model,” Toxicology and Applied Pharmacology, vol. 252, no. 2, pp. 201–210, 2011.
[33]
A. Nakorchevsky, J. A. Hewel, S. M. Kurian et al., “Molecular mechanisms of chronic kidney transplant rejection via large-scale proteogenomic analysis of tissue biopsies,” Journal of the American Society of Nephrology, vol. 21, no. 2, pp. 362–373, 2010.
[34]
B. H. ？zdemir, A. A. ？zdemir, T. Colak, S. Sezer, and M. Haberal, “The influence of tubular phenotypic changes on the development of diffuse interstitial fibrosis in renal allografts,” Transplantation Proceedings, vol. 43, no. 2, pp. 527–529, 2011.
[35]
B. A. Julian, S. Wittke, M. Haubitz et al., “Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases,” World Journal of Urology, vol. 25, no. 5, pp. 467–476, 2007.
[36]
S. Decramer, A. G. de Peredo, B. Breuil et al., “Urine in clinical proteomics,” Molecular and Cellular Proteomics, vol. 7, no. 10, pp. 1850–1862, 2008.
[37]
D. Fliser, J. Novak, V. Thongboonkerd et al., “Advances in urinary proteome analysis and biomarker discovery,” Journal of the American Society of Nephrology, vol. 18, no. 4, pp. 1057–1071, 2007.
