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Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

[PDF] Ovalle_Transplantation.pdf (475.8Kb)
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URI: http://hdl.handle.net/10481/30964
ISSN: 1932-6203
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Author
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
Editorial
Public Library of Science (PLOS)
Materia
Biopsy
 
Creatinine
 
Kidneys
 
Renal analysis
 
Renal ischemia
 
Renal system
 
Renal transplantation
 
Transplantation immunology
 
Date
2009
Referencia bibliográfica
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]
Sponsorship
This work was funded by the Fondo de Investigaciones Sanitarias (Grants PI021505, and PI051197).
Abstract
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.
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