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Presenter: Conxita, Jacobs, Barcelona, Spain
Authors: Conxita Jacobs, Eduard Sarró, Sonia Caparrós, Carme Cantarell, M. Angeles Montero, Francisco Moreso, Daniel Serón, Joan López, Anna Meseguer
Intrinsic allograft failure continues to be a major problem in kidney transplantation and is responsible for late allograft loss. Although immunological responses remain the leading factor in the pathogenesis of chronic rejection, recent studies have indicated a complexity of findings, including etiologies that are both immune and non-immune. Non immunological factors, such as donor organ quality, initial ischemic injury, calcineurin inhibitor (CNI) toxicity, hypertension, and hyperlipidemia, also contribute to progressive chronic allograft injury. Because there is a need to identify markers of graft failure more sensitive than serum creatinine and it would be helpful to distinghish between different types of injury, our laboratory is currently focused on the identification of new biomarkers that could specifically detect CNI toxicity or hypoxia-related adverse effects, from other noxious effectors on proximal tubular cells. We first focused on defining a proteomic profile in CsA-treated HK-2 proximal tubule cells, to distinguish the direct impact of CsA from overlapping haemodynamically mediated phenomena that occur in an in vivo system. By means of high-throughput differential proteomic analyses and mass spectrometry techniques in CsA and vehicle-treated cells we determined proteins that change their expression in the presence of CsA (Puigmule et al. Nephrol Dial Transplant. 2009; 24(9):2672-86). While these proteins could be used in kidney biopsies, they were no useful as early biomarkers in plasma or urine of trasplanted patients. At present, our work is focused towards identification of secreted proteins in conditioned media of HK-2 cells, treated with CsA and FK506, or exposed to hypoxia, using the same high-throughput differential proteomic approach. Other nephrotoxicants known to induce tubular damage are also used to distinguish specific than general injury biomarkers. Those potential biomarkers would be validated in urine and plasma samples of transplanted patients under anti-calcineurin treatment, before and after transplantation.
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