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Expression of Complement Components Differs Between Kidney Allografts from Living and Deceased Donors

Maarten Naesens^*,, Li Li^*, Lihua Ying^*, Poonam Sansanwal^*, Tara K. Sigdel^*, Szu-Chuan Hsieh^*, Neeraja Kambham, Evelyne Lerut, Oscar Salvatierra^*,||, Atul J. Butte^¶ and Minnie M. Sarwal^*

Departments of *Pediatrics,
Pathology, and
^||Surgery and
^¶Stanford Medical Informatics, Department of Medicine and Pediatrics, Stanford University School of Medicine, Stanford, California; and Departments of
Nephrology and Renal Transplantation and
Morphology and Molecular Pathology, University Hospitals Leuven, Leuven, Belgium

Correspondence: Dr. Minnie M. Sarwal, Stanford University, G320, 300 Pasteur Drive, Stanford, CA 94305. Phone: 650-724-3320; Fax: 650-723-4517; E-mail: msarwal{at}stanford.edu

Received for publication November 5, 2008. Accepted for publication February 16, 2009.

A disparity remains between graft survival of renal allografts from deceased donors and from living donors. A better understanding of the molecular mechanisms that underlie this disparity may allow the development of targeted therapies to enhance graft survival. Here, we used microarrays to examine whole genome expression profiles using tissue from 53 human renal allograft protocol biopsies obtained both at implantation and after transplantation. The gene expression profiles of living-donor kidneys and pristine deceased-donor kidneys (normal histology, young age) were significantly different before reperfusion at implantation. Deceased-donor kidneys exhibited a significant increase in renal expression of complement genes; posttransplantation biopsies from well-functioning, nonrejecting kidneys, regardless of donor source, also demonstrated a significant increase in complement expression. Peritransplantation phenomena, such as donor death and possibly cold ischemia time, contributed to differences in complement pathway gene expression. In addition, complement gene expression at the time of implantation was associated with both early and late graft function. These data suggest that complement-modulating therapy may improve graft outcomes in renal transplantation.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673