Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation O'Valle Ravassa, Francisco Javier García Del Moral Garrido, Raimundo Benítez Ortúzar, María Del Carmen Martín Oliva, David Gómez-Morales, Mercedes Aguilar Peña, David Aneiros-Fernández, José Hernández-Cortés, Pedro Osuna Ortega, Antonio Moreso, Francesc Serón, Daniel Oliver Pozo, Francisco Javier García Del Moral Garrido, Raimundo Biopsy Creatinine Kidneys Renal analysis Renal ischemia Renal system Renal transplantation Transplantation immunology Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). [Materials and Methods] Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. [Results] PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. 2014-03-19T10:06:04Z 2014-03-19T10:06:04Z 2009 info:eu-repo/semantics/article O'Valle, F.; et al. Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation. Plos One, 4(9): e7138 (2009). [http://hdl.handle.net/10481/30964] 1932-6203 doi: 10.1371/journal.pone.0007138 http://hdl.handle.net/10481/30964 eng info:eu-repo/semantics/openAccess Public Library of Science (PLOS)