TOPIC DISCUSSION: Eculizumab and Kidney Transplantation? What is the future

Eculizimab is now starting to be used at some transplant centers for treatment of antibody mediated rejection.  What is that and why?  Eculizimab(Solaris) is a monoclonoal ab directed against the complement protein C5.  This antibody blocks the cleavage of C5 and halts the process of complement mediated cell destruction. It has been used effectively and FDA approved for paroxymal nocturnal hemoglobinuria. 

               In reviewing the literature for renal diseases, I found mice studies for many connective tissue diseases and nice JASN paper from 2007 in renal transplantation use. Mice with this drug given prior had zero rejection vs placebo. In 2009, Early results from a Mayo Clinic research study were presented at ATC 2009. Results showed that eculizumab prevents antibody-mediated kidney transplant rejection by inhibiting the immune system's activation of one of the body's important defense mechanisms -- the complement system. Antibody-mediated rejection is a major barrier to transplant in patients with antibodies against their living donors sometimes called "positive crossmatch kidney transplants."

            The benefit was mainly in high risk PRA and highly immunized patients. Increasingly recognized as a major problem, high levels of these antibodies delay transplantation, as evidenced by the approximately 7,000 people on the United Network for Organ Sharing (UNOS) kidney waiting list who are still looking for a match. Mayo Clinic has long been a leader in devising innovative approaches to help this challenging group of kidney patients, and these latest findings about eculizumab add to the expertise and options offered to patients.  This suggests a novel way to block antibody-mediated tissue injury. The Mayo team showed that eculizumab blocks the part of the immune system known as the complement system, which initiates tissue destruction. In this study, 10 positive crossmatch kidney transplant patients were treated with eculizumab. None of the treated patients developed antibody-mediated rejection compared to historical controls in which 60 percent with similar levels of antibody would have developed antibody-mediated rejection.  
    This is a big leap in transplantation but long term effects are unknown. How many doses to be given? How long does the effect last is unclear? And if on this drug, rejection occurs, will C4D be negative. Also, interesting findings like this take us back to diseases like lupus and perhaps its use in those diseases as a good induction agent.