Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Remarkable 107-year-old kidney with a 49-year of long-term allograph survival through continuous azathioprine monotherapy.

BACKGROUND: The main goal of kidney allograft transplantation is to improve survival in patients with end-stage kidney failure. Herein, we report a 49-year long-term allograft survival with non-identical human leukocyte antigens (HLA). The purpose of this study was to report the successful clinical outcome of 49 years of transplant survival in a 79-year-old patient with a 107-year-old kidney undergoing continued immunosuppressive monotherapy. MATERIAL AND METHODS: The patient was evaluated clinically and immunologically with HLA typing and anti-HLA antibodies before transplantation. Post-transplant, the patient's clinical and immunological survival were monitored for 49 years. The state of the chimerism was assessed using the polymerase chain reaction to amplify 24 short tandem repeats using a DNA thermocycler and DNA analyzer. RESULTS: The patient and donor were haploidentical and the patient was treated with azathioprine monotherapy. Donor-specific antibodies were detected only for the HLA-DPB1* 03:01 mismatch. This patient developed multiple skin tumors 26 years after transplant, which were successfully treated with topical therapy or surgical removal. The patient developed an intestinal adenocarcinoma 43 years after kidney transplantation, which was surgically removal; six years later, adenocarcinoma was diagnosed in a finger, followed by axillar and hepatic metastases. After 49 years of graft survival of a kidney of 107 years old in a patient with 79 years of age, the patient's health worsened with severe dehydration, anemia, and bacterial infection. The patient was hospitalized with a serum creatinine level of 3.45 mg/dL, urea level of 188 mg/dL, and estimated glomerular filtration rate of 22 mL/1.72 m2; septicemia developed and was treated with antibiotics. The patient had poor clinical progress, was intubated, and later died due to septic shock. CONCLUSIONS: To the best of our knowledge, this is the first case of a 107-year-old kidney, transplanted into a recipient who was treated with azathioprine monotherapy for 49 years.

[Identifying the specific causes of kidney allograft loss: A population-based study]. / Étude des étiologies spécifiques de perte des greffons rénaux : place du rejet médié par les anticorps et approche en population.

INTRODUCTION: Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. METHODS: A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. RESULTS: There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). CONCLUSION: The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival.