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Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

Niamh Kieran^*, Xiaotong Wang, James Perkins, Connie Davis^*, Elizabeth Kendrick^*, Ramaswamy Bakthavatsalam, Nancy Dunbar, Paul Warner, Karen Nelson, Kelly D. Smith, Roberto F. Nicosia, Charles E. Alpers, Nicolae Leca^* and Jolanta Kowalewska

*Department of Medicine, Division of Nephrology,
Department of Pathology, and
Division of Transplant Surgery, University of Washington, Seattle, Washington; and
Puget Sound Blood Center, Seattle, Washington

Correspondence: Dr. Niamh Kieran, Division of Nephrology, University of Washington, BB1271 Health Sciences Building, 1959 N.E. Pacific Street, Box 356521 Seattle, WA 98195-6521. Phone: 206-543-3792; Fax: 206-685-8661; E-mail: niamh70{at}u.washington.edu

Received for publication February 19, 2009. Accepted for publication July 1, 2009.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 ± 13 versus 38 ± 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

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