Pathogenetic and diagnostic considerations of C4d and fibrin in acute antibody-mediated rejection of renal transplant

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Graft failure remains a major problem after renal transplantation. Identification of acute humoral rejection (AHR) in biopsy specimens has been problematic because no morphologic feature described to date is either pathognomonic or universal. In the present study, we investigated the role of both C4d and fibrin as diagnostic tools for the early assessment of AHR.

Patients and methods

This work represents a retrospective study on 53 renal allograft biopsies at the period between January 2005 and May 2008 at the Urology and Nephrology center (Mansoura Faculty of Medicine). Alternate slides were stained with hematoxylin and eosin stains, periodic acid-Schiff stain, and Masson trichrome stain as routine workup following standard procedures for staining. Cases of AHR were previously stained for C4d using the immunohistochemical technique. For the immunofluorescent staining, the pretreated sections are stained by monoclonal C4d and fibrinogen antibodies using the indirect immunofluorescent method.

Results and conclusion

Statistically significantly higher C4d positivity by immunofluorescence staining in cases of AHR was found in comparison with C4d immunohistochemical staining (P<0.01). The fibrin positivity in cases of AHR was higher than that in cases of acute cellular rejection (ACR), which was statistically significant (P<0.05). There was no significant relationship between consanguinity and recipient patients (P value>0.05). This study concluded that C4d plays a role in the detection and diagnosis of AHR cases and this can modify the protocol of treatment for better graft survival. Fibrin detection is important for the diagnosis of missed cases of fibrinoid necrosis that are specific for AHR cases and were not confirmed by routine light microscopic staining.

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