Successful living donor kidney transplantation across HLA and ABO incompatibilities

A 56-year-old white female presented for evaluation for kidney transplantation in November 2003. Her end-stage renal disease (ESRD) was presumed due to medullary sponge kidney associated with stones and infection and she had started haemodialysis in April 2003. Other medical history included hypertension and anaemia. She was otherwise well. She had had four pregnancies and had received blood transfusions. Examination was unremarkable. Initial tests showed blood group ABO-O. Her current panel reactive antibody (PRA) was 64% by the complement-dependent cytotoxicity (CDC) method and the peak PRA, 5 months prior to that, was 100%. Flow PRA screening confirmed IgG antibodies against class I and II human leukocyte antigens (HLA). The cause of the sensitization to HLA antigens was presumed to be the pregnancies and transfusions. Her 37-year-old son was the only potential living donor but he was ABO-A1; furthermore, she had a positive CDC crossmatch against his T and B lymphocytes. The patient’s baseline anti-A antibody titre was 1:128 (Figure 1). Because of her high sensitization to HLA antigens, the idea of a transplant across the HLA and ABO barrier was discussed with the patient. She was advised to wait several months to see if her PRA or crossmatch titres fell with rituximab therapy. She was vaccinated against pneumococcus and meningococcus in the event that a splenectomy would be included in her immunosuppressive protocol. She received rituximab 375mg/m in March and April of 2004. However, the crossmatch remained strongly positive and the PRA remained high (Table 1). After detailed discussion of the risks vs benefits, the patient and son gave informed consent to proceed with transplantation of a kidney from the son to the mother. Before 4 weeks of the transplant, she began receiving thrice-weekly plasmapheresis and daily tacrolimus plus mycophenolate mofetil (MMF). She was given 10 g of IgG intravenously after each plasmapheresis session. The anti-microbial prophylaxis was sulfamethoxazole-trimethoprim (SMX-TMP) and acyclovir. On 20 December 2004, the T-cell and B-cell crossmatch against her donor were negative and the anti-A titre (IgG titer by enhanced antiglobulin assay) was 1:2 (Figure 1). A third dose of rituximab was given, and she underwent kidney transplantation the next day. A laparoscopic handassisted splenectomy was also performed. There were no intra-operative complications and the allograft produced urine immediately. She received five more sessions of plasmapheresis in the first 10 post-operative days, to maintain anti-A titres 1 : 4. The patient was discharged 1 week after surgery with a plasma creatinine of 63 mmol/l. Immunosuppression was now tacrolimus, MMF and prednisone. After 2 weeks of the transplant, the creatinine rose to 141 mmol/l, and an urgent allograft biopsy was performed. The anti-A titre was 1 : 4 and the crossmatch was positive against donor Tand B-cells by flow cytometry. The biopsy showed mild focal neutrophil capillaritis, acute tubular injury and intraluminal calcifications. There was diffuse staining for C4d in the peritubular capillaries. Interestingly, she had started p.o. phosphate 1–2 days prior to the elevation in plasma creatinine. The possibility of acute calcium—phosphate precipitation in the allograft [1] was, therefore, entertained and the phosphate was stopped. The presumed acute antibodymediated rejection was treated with four sessions of plasmapheresis over 10 days (followed by 10 g IgG) and pulse IV methylprednisolone. The plasma creatinine fell quickly to 71 mmol/l. A repeat flow cytometry crossmatch against donor Tand B-cells was negative. The patient was continued on immunosuppression with tacrolimus, MMF and prednisone. No further Correspondence and offprint requests to: Colm C. Magee, MD, Renal Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. Email: cmagee@partners.org Nephrol Dial Transplant (2007) 22: 602–604