#WTC2014: New weapons in the fight against antibodies? Maybe… (part 2)

2. C1 inhibitor (C1INH)

If you remember your allergy immunology rotation you may remember that this drug is approved for hereditary angioedema. It works proximally in the complement cascade and blocks the classic and MBL pathway of complement activation. With all of the interest eculizumab received in kidney transplantation its no suprise that studies are now looking at other targets in the complement cascade.

The Cedars Sinai group looked at the use of C1 INH to prevent antibody mediated injury. 20 patients were desensitized with IVIg and rituximab. If they had a positive flow cxm with a potential donor they received C1INH or placebo intraop then for 7 wks post transplant. No patient had AMR while receiving C1 INH but 2 had AMR after. In the placebo group 1 patient had AMR 2 wks post transplant and 2 more patients had AMR after the study period. As expected C1 INH levels, C3 and C4 levels were higher in the group that received C1INH.

The Hopkins group also evaluated C1INH in a small multicenter study of 18 pts with mild to moderate AMR. They gave C1INH or placebo every 2 wks for 7 wks in addition to standard AMR therapy. Renal function tended towards improvement in the C1 INH group but at 20 days post treatment there was no difference in histology. However, 3-6 months after therapy 3/7 of the placebo group displayed new transplant glomerulopathy vs 0/7 in the C1INH group.

Again, in both these studies there were no SAEs related to the drug. Similar to TCZ, more studies will be required to evaluate the role, if any, of C1 INH in kidney transplantation.   As we are beginning to see, there are many different phenotypes of antibody mediated kidney injury. As we develop more agents we will need to narrow down which agents work best in which specific phenotypes.

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

Check out more of eAJKD’s coverage of the 2014 World Transplant Congress here and on Twitter (@eAJKD)!

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