C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation
Abstract
To the Editor: Although studies of porcine kidney xenotransplantation in nonhuman primates (NHPs) and brain-dead humans have improved our understanding of anti-xenograft immune responses (1–3), the optimal immunosuppression regimen for living human recipients is unknown (3). Prior NHP studies suggest that complement plays an important role in immune-mediated injury of xenografts (4), but the benefits of pharmacologic complement inhibition in human xenograft recipients have yet to be established. Here, we report the histologic outcomes of a series of brain-dead human recipients of a porcine kidney xenotransplant using exclusively FDA-approved medications, with and without anti-C5 monoclonal antibody. Three male decedents, aged 57, 65, and 53 years, respectively, underwent bilateral native nephrectomies, followed by crossmatch-compatible xenotransplantation (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI175996DS1) with 10 gene-edited (10GE) pig kidneys that expressed 2 human transgenes responsible for classical complement cascade inhibition (CD46 and DAF) (2) with standard immunosuppression (Supplemental Methods). There was no evidence of hyperacute rejection in any decedent. Decedents 2 and 3 received anti-C5 monoclonal antibody therapy (eculizumab) 24 hours prior to (1,200 mg) and 24 hours after (900 mg) xenotransplantation. Decedent 1 native kidney and 10GE porcine donor kidney biopsies were histologically normal…
How strong is the evidence?
Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- In silico strategies for modeling RNA aptamers and predicting binding sites of their molecular targets
- Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin delivery
- Anti-phytopathogenic and plant growth promoting potential of endophytic fungi isolated from Dysoxylum gotadhora
- Mercury toxicity causes iron and sulfur deficiencies along with oxidative injuries in alfalfa (Medicago sativa)
- Suppression of lncRNA GAS6-AS2 alleviates sepsis-related acute kidney injury through regulating the miR-136-5p/OXSR1 axis in vitro and in vivo
- Assessing the Protective Effect of Moringa oleifera Extract against Bone Metastasis: An In Vitro Simulated Digestion Approach
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.