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On the Intraoperative Molecular Status of Renal Allografts after Vascular Reperfusion and Clinical Outcomes

Yingyos Avihingsanon^*, Naili Ma^*, Martha Pavlakis^*, W. James Chon^*, Marc E. Uknis, Anthony P. Monaco, Christiane Ferran, Isaac Stillman, Asher D. Schachter^,||, Christina Mottley^*, Xin Xiao Zheng^* and Terry B. Strom^*,

^* Department of Medicine, Department of Surgery, and Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School; Department of Pediatrics, Children’s Hospital and Harvard Medical School; and ^|| Children’s Hospital Informatics Program, Children’s Hospital Boston

Address correspondence to: Dr. Terry B. Strom, Transplant Research Center, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine-1; Room 1026, 77 Avenue Louis Pasteur, Boston MA 02115. Phone: 617-667-0850; Fax: 617-667-0923; E-mail: tstrom{at}bidmc.harvard.edu

Many hypothesize that subtle inflammation and immune activity detected in the intraoperative period are linked to adverse postkidney transplant clinical outcomes. To this end, renal allografts were analyzed for expression of pro-inflammatory, inflammation-induced adhesion molecules, immune activation as well as anti-apoptotic genes expressed 15 min after vascular reperfusion (zero-hour) to determine whether this analysis can aid in predicting the occurrence of delayed graft function (DGF), acute rejection (AR), and the quality of graft function at 6 mo. Intraoperative biopsies were obtained from 75 consecutively performed renal allografts in which consent was obtained 15 min after vascular reperfusion. These biopsies were analyzed by quantitative real-time PCR for transcription of 15 select genes and by standard histopathology. Posttransplant clinical outcomes were also analyzed in respect to intraoperative transcriptional profiles and clinical parameters available at the time of transplantation. This study demonstrates that a limited and hypothesis-driven PCR-based transcriptional profile of the zero-hour kidney biopsy predicts posttransplant clinical outcomes including DGF, early AR, and the quality of renal function 6 mo posttransplantation. For some clinical endpoints, the combined use of molecular analysis and established clinical indicators available at the time of transplantation further enhances the quality of prognosis. The transcriptional profiling data provide absolutely essential data to the predictive models, particularly with respect to AR and renal function 6 mo posttransplantation.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673