THERAPEUTIC STRATEGIES FOR KIDNEY TRANSPLANTATION

B.E. Lonze¹, N.N. Dagher¹, C.E. Simpkins¹, D.L. Segev¹, A.L. Singer¹, S. Cohney², N. Alachkar³, R.A. Montgomery^1
1Surgery, Johns Hopkins, Baltimore/MD/UNITED STATES OF AMERICA, ², Royal Melbourne Hospital, Parkville/AUSTRALIA, ³Medicine, Johns Hopkins, Baltimore/MD/UNITED STATES OF AMERICA

Body: BACKGROUND: Renal impairment is common in patients with APS, and for those who progress to end-stage renal disease, the mortality risk associated with dialysis dependence is compounded by the risk of losing of vascular access due to venous thrombosis. Small, published case series suggest that early graft loss due to recurrence of APS occurs in as many as 50% of transplant recipients. The complement system has been implicated in the pathogenesis of microvascular thrombosis associated with APS. We hypothesize that the terminal complement inhibitor, eculizumab, when administered together with systemic anticoagulation, will prevent recurrent APS and improve the outcomes in these patients. METHODS: Three patients with APS were treated with eculizumab in conjunction with continuous systemic anticoagulation and underwent living donor renal transplantation. Eculizumab (1200mg) was given on the night before transplantation and was redosed at 900mg on POD1 and weekly thereafter for one month. This was followed by bi-monthly doses of 1200mg and was continued until antiphospholipid antiobody (APLA) titers returned to baseline. Outcomes of patients treated with eculizumab were compared to historical controls who received live donor transplants and were managed with systemic anticoagulation alone. RESULTS: Graft survival in patients treated with eculizumab was 100% over a median follow-up period of 5 months (range 1-9 months). There were no instances of clinically detectable APS in this group. Both of the historic control patients experienced early APS recurrence. One graft was lost due to thrombosis within two weeks of transplantation. The other graft was severely impaired and emerged from the APS crisis with a serum creatinine of 2.6 mg/dl. One patient in the treatment group with a history of catastrophic APS manifest a profound perioperative surge in APLA titers without graft impairment or thrombosis (Figure 1). CONCLUSION: Patients with APS have historically had poor outcomes and high rates of recurrence after renal transplantation, despite the use of systemic anticoagulation. Several lines of evidence implicate the complement cascade in the development of vascular thrombosis in APS. Eculizumab has shown promise in enabling successful renal transplantation in our APS patient series and warrants investigation on a larger scale.

Disclosure: All authors have declared no conflicts of interest.