Would you recommend complement testing in a kidney transplant recipient with chronic antibody-mediated rejection and biopsy-proven thrombotic microangiopathy to determine the need for eculizumab?

There is basic and translational data to support the role of IL-6 in acute and chronic humoral rejection, with small single-center trials investigating the use of agents that blockade IL-6/IL-6 receptor interactions for humoral rejection in kidney transplantation. In many of these studies, there is a decrease in donor-specific antibodies. From a basic perspective, IL-6 is a driver of B-cell autoantibody production, so this makes sense. It is also a pleiotropic cytokine that impacts multiple arms of the immune system as well. Our center has used Tocilizumab for several patients with evidence of ongoing humoral rejection (by surveillance biopsy, so subclinical) who failed standard-of-care treatment with plasma exchange, IVIG, and Rituximab. In our limited experience, this appears to be helping with resolving inflammation and preserving renal function.

We have limited experience using Eculizumab in our program. I would use it for refractory humoral rejection causing progressive acute renal injury. My opinion is to use Eculizumab more in the acute setting, where active humoral rejection causing renal dysfunction is evident clinically and by renal biopsy. For chronic cases, I believe that instead of using a “band-aid” – limiting subclinical complement-mediated injury, is to try to address the cause/source itself (decreasing donor-specific Ab production). I would use Toci in this case, unless there is evidence of progressive acute injury.