Backtable Intra-Arterial Administration of C1 Esterase Inhibitor to Deceased Donor Kidney Allografts Improves Post-Transplant Allograft Function: Results of a Randomized Double-Blind Placebo-Controlled Clinical Trial.
Huang, E., et al.American Journal of Transplantation 2025 [record in progress].
Aims
To determine whether a single back-table intra-arterial infusion of C1-esterase inhibitor (C1INH, 500 U Berinert®) into high-risk deceased-donor kidney allografts reduces delayed graft function (DGF) and/or improves early and intermediate post-transplant graft performance, while remaining safe.
Interventions
Following cold storage and vascular flushing, the renal artery of each study kidney was clamped and instilled with 10 mL heparinised saline followed by 10 mL containing 500 U C1INH; the clamp remained until implantation. Control grafts received the same volume of 0.9 % saline. All other peri-operative care (lymphocyte-depleting induction, tacrolimus-based maintenance, standard prophylaxis) was identical and blinded.
Participants
45 adult kidney recipients of deceased donor kidneys determined to be high risk for DGF (KDPI > 80 %, or DCD, or CIT > 24 h, or AKI donors).
Outcomes
Primary outcomes were incidence of DGF (≥ 1 dialysis session in first 30 d, excluding isolated hyperkalaemia treatments) and eGFR trajectory to 6 months. Secondary/ mechanistic outcomes: number/duration of dialysis sessions, patient/graft survival to 6 months, post-reperfusion biopsy staining for C1INH and complement split products and systemic complement and bradykinin activity.
Follow-up
30 months (median)
CET Conclusions
The authors present a small well-designed, well-blinded RCT assessing kidney delivered C1INH in static cold storage prior to implantation. Despite not seeing a meaningful reduction in DGF (50 % vs 45 %), they did find a clinically and statistically meaningful rise in eGFR at 1 month (median 39 vs 21 mL/min/1.73 m²) that persisted through to 30 months (54 vs 43 mL/min/1.73 m²). The kidney biopsies confirmed intragraft C1INH retention and reduced C4d/C3b deposition, supporting on-target, local complement inhibition, with no systemic complement suppression or excess adverse events. While the results are similar to the group’s previous work with C1INH as a systemic recipient agent, they are striking in a kidney delivered setting. C1INH is primarily a soluble molecule rather than membrane bound, so with only relatively small amounts in the kidney from the SCS delivery being sufficiently active during the reperfusion process to locally attenuate the complement mediate aspect of IRI rather than being immediately flushed out systemically. However, the study is robust, rigorously blinding, with mechanistic tissue validation, and durability of the functional signal over the 30 months which is reassuring. There are some limitations: small scale, single centre, baseline sex imbalance, exclusion of pump-preserved kidneys, and under-power for DGF or safety rarities, but these are broadly speaking minor. This is an exciting study of a kidney delivered therapy, and if reproduced in a larger multicentre trial, a simple 500-U intra-arterial C1INH wash could become a low-cost, low-toxicity add-on to kidney implantation, potentially upgrading borderline deceased-donor kidneys by partially mitigating complement-driven IRI and improving medium-term function, even if not effective at lowering DGF incidence.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT04696146