Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Delayed graft function(DGF) is defined as need for dialysis early post-transplant. DGF is related to ischemia reperfusion injury (IRI) that diminishes allograft function and may be complement dependent. We previously reported on outcomes of a placebo-controlled trial of C1 esterase inhibitor (C1INH) to prevent IRI/DGF in at risk kidney transplant recipients (AJT, November 2018). Although the primary end points were not met, we found a significant benefit in improved eGFR at 1 year in C1INH treated patients. We hypothesized that C1INH blocks early complement activation and inflammatory events that may result in less AKI->CKD progression. Here we analyze long-term outcomes (3.5 years) in this patient cohort.
*Methods: 70 patients receiving cadaver kidney transplants at risk for DGF were randomized to receive C1INH 50 U/kg (#35) or placebo (#35) intraoperatively and at 24 hours. The primary end point was need for hemodialysis during the first week post-transplant. Assessments of GFR, pre-transplant biopsies and dialysis dependency were accomplished for the 1st year. Complications and safety of therapy was recorded. Long-term analysis of renal function as well as patient and graft survival were completed up to 3.5 years post-transplant.
*Results: Although the primary end-point was not met,significant improvements in renal function were seen at one year in C1INH patients (p=0.006)and at 3.5 years post-transplant (mean eGFR C1INH 55.6 cc/min [slope +.5] v. placebo 37.5cc/min. slope -4.7](Fig.1). C1INH treatment was also associated with significant improvements in graft survival at 3.5 years with 7 graft losses in the placebo group v. 0 in C1INH (p=0.0007) (Fig. 2). Three patient deaths were noted in the C1INH group, deemed unrelated to treatment. No significant adverse events were noted with C1INH.
*Conclusions: Treatment of patients at risk for IRI/DGF result in improvements in long-term allograft function and graft survival. This suggest that C1INH blocks early IRI induced gene activation events that lead to progression from AKI->CKD. C1INH could improve utilization of kidneys discarded for fear of poor graft function and early loss.
To cite this abstract in AMA style:Jordan S, Huang E, Ammerman N, Choi J, Aubert O, Kumar S, Loupy A, Peng A, Kim I, Najjar R, Puliyanda D, Brennan T, Sethi S, Vo A. C1 Esterase Inhibitor (C1INH) Treatment at Kidney Transplant Improves Long-Term Outcomes in Patients at Risk for Ischemia/Reperfusion Injury & Delayed Graft Function [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/c1-esterase-inhibitor-c1inh-treatment-at-kidney-transplant-improves-long-term-outcomes-in-patients-at-risk-for-ischemia-reperfusion-injury-delayed-graft-function/. Accessed September 29, 2020.
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