*Purpose: While immunologically challenging and controversial, we report a successful case of same donor staged simultaneous liver-kidney transplant (SLK) in a highly sensitized child against a positive cytotoxic crossmatch (XM) and high Class I/II donor-specific antibody (DSA) titers.

*Methods: A 34 kg, 15-year-old male with autosomal recessive polycystic kidney disease (on hemodialysis and with recurrent variceal bleeding) was listed for SLK. Pre-transplant calculated panel reactive antibody (cPRA) at 2000 mean fluorescence intensity (MFI) remained 98% despite attempts at immunomodulation. Many Class I/II antibodies (from blood transfusions) were present, with anti-A2 (MFI: 18329) and -DQ7 (MFI: 2045) predominating. Awaiting SLK, the patient became more unstable with worse infections, malnutrition, and more bleeding. PELD was 40 at the time of liver transplant (LT).

*Results: A 5 HLA mismatch donor became available; virtual, cytotoxic and flow pronase XMs were positive [T-cell flow cytometry at 11,793 (< 2,000 MFI = negative), B cell flow cytometry at 11,224 (<3,000 MFI = negative)]. Given the deteriorating clinical status and failed attempts at finding an immunologically more compatible donor over the prior 2 years, transplant against a positive XM was deemed appropriate. Rituximab (375mg/m2) was given prior to LT, and, with intra-operative continuous renal replacement therapy (CRRT), the LT was completed without difficulty requiring only 2 units of blood. Methylprednisone (500mg) (MP) and Basiliximab (20mg) were given during the anhepatic phase. The patient was extubated and stabilized overnight on CRRT. A flow XM obtained 30 minutes after LT was negative for T cell flow (MFI 202), while B cell flow remained positive (MFI 26,630), presumably related to Rituximab. The donor kidney was pumped overnight, and XMs were repeated every 4 hours. Tacrolimus (Tac) and Cellcept (MMF) were initiated. On return to the operating room 18 hours later, the T cell flow XM remained negative (MFI 83), and the B cell flow XM was weakly positive (MFI 12,516). Eculuzimab (900mg) and a second dose of MP (250mg) were given at renal graft perfusion. Immediate urine output was observed. Normalization of liver and kidney markers and graft function were noted. Serum creatinine was stable at 0.5mg/dL by discharge. DSAs were monitored daily until discharge and remained negative. Discharge was achieved on post-operative day 14 on Tac, oral prednisone and MMF. At 5 months post staged SLK, there is no evidence of de-novo DSA but excellent liver and kidney function.

*Conclusions: We present the successful staged SLK of a complex, highly sensitized child in the setting of high titers of Class I/II DSAs against positive XMs. Sophisticated immunologic management and delay of kidney transplantation by 18 hours, presumably allowing the liver allograft to absorb circulating DSAs and T-cells, resulted in excellent graft function without evidence of hyperacute or acute rejection.

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