Diagnostic value of C4d in renal biopsies.

PURPOSE OF REVIEW: Capillary C4d is now an established marker of antibody-mediated rejection in graft biopsies. The technique is widely used to further define the clinical relevance of humoral alloreactivity in various patient subgroups. These include highly sensitized patients, recipients with late graft failure and also some with 'stable' graft function.

RECENT FINDINGS: The C4d technique compares favourably with other techniques that are explored, for example detection of C3d. Capillary C4d can be associated with any graft pathology, including transplant glomerulopathy. C4d is related to circulating alloantibodies but not autoantibodies, and is probably not derived from local sources. Presensitization and de-novo sensitization are important scenarios of humoral alloreactivity that require refined analysis and treatment.

SUMMARY: Detection of C4d in graft biopsies has emerged as an important tool that could substantiate the clinical significance of antibody-mediated rejections. The comprehensive analysis of humoral alloreactivity in the posttransplantation period is still ongoing and will hopefully result in improved patient care and better long-term graft survival.