Monitorización sérica e histológica del rechazo mediado por anticuerpos en trasplante renal

Abstract

Kidney transplantation is considered the treatment of choice for patients with end-stage renal disease. It is associated with improved survival, better quality of life and reduced costs when compared with dialysis. Throughout the years, the progress in immunosuppression, the improvement in surgical techniques and a better understanding of transplant immunology have produced an increase in both patient and graft survival short-term, notwithstanding in medium and long-term outcomes. Two major developments have taken place over the last decade: the development of new techniques to detect HLA antibodies, and the histological characterization of antibody-mediated rejection. The aim of this thesis has been to expand the knowledge of antibody-mediated rejection by addressing the issue from these two points of view: HLA antibody serological testing with new techniques and histological characterization of humoral rejection. To that end, we have analyzed a large cohort of transplant patients with pre and post-transplant anti-HLA antibodies determined by Luminex technologies. Patients with preformed donor specific antibodies show worse graft survival and greater risk of antibody-mediated rejection, regardless potential DSA clearing after transplantation. Furthermore, we evaluated the impact of typically less immunogenic antibodies believed to be less relevant in the transplant field thus far, such as HLA DP antibodies, albeit detectable by newer solid phase techniques. In our experience, 10% of transplant patients show HLA DP antibodies as detected by Luminex assay both pre and post-transplant. The presence of these antibodies does not seem to modify graft survival Histologically, we have shown that antibody-mediated rejection is a common diagnosis most often seen in late kidney graft biopsies according to the Banff 2013 classification criteria; antibody-mediated rejection also shows worse prognosis compared to other histological categories. Eventually, we have delved into the analysis of the antibody-mediated rejection category by comparing the Banff 2009 classification to the new antibody-mediated changes from Banff 2013. According to our results, Banff 2013 classification provides a more accurate diagnosis of antibody-mediated rejection.

Date of Award	6 Jun 2018
Original language	Spanish
Supervisor	Marta Crespo Barrio (Director), Julio Pascual Santos (Director) & Juan Pedro Botet Montoya (Tutor)