#WTC2014: Detection of C3d binding donor specific antibodies at diagnosis of humoral rejection predicts renal graft loss

In kidney transplantation one of the largest challenges is in understanding antibody-mediated injury. During the first plenary session at the World Transplant Congress, Dr. Sicard from France presented data that may help prognosticate outcomes after antibody-mediated rejection. In the study they looked at 69 patients who had humoral rejection and screened them for complement activation by evaluating for (1) C4d tissue staining (2) C1q binding of serum donor specific antibodies (DSA) and (3) C3d binding of serum DSA. Treatment of humoral rejection included steroids, IVIg, plasma exchange, and rituximab. The authors found that only 31% of patients tested positive for all 3 assays. Patients with a positive C1q assay had a nonsignificant trend towards worse graft survival while C3d binding revealed a clear and significant association with graft loss. This was despite similar histologic lesions and treatment. In a multivariate analysis this was confirmed. Interestingly this association held true even in patients with low-titer C3d antibodies. This association was confirmed in 38 additional patients who had humoral rejection. The authors hypothesize that C3d binding DSA may be a better marker of antibody-induced injury than simply checking for DSA or even C1q binding DSA as C3d activation occurs late in the complement cascade. Besides predicting outcome further study with this assay may help identify patients who will benefit from complement blockade as a treatment for humoral rejection.

Post written by Dr. Vinay Nair, eAJKD Advisory Board member.

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