Impact of persistent preformed and de novo donor-specific antibodies detected at 1 year after kidney transplantation on long-term graft survival in Japan: a retrospective study.

BACKGROUND: We evaluated the impact of persistent preformed donor-specific antibody (DSA) and de novo DSA (dnDSA) detected at 1 year posttransplantation on long-term death-censored graft survival. METHODS: One hundred and sixty adult patients who received living kidney allograft with pretransplant-negative T-cell complement-dependent cytotoxicity crossmatch (CDCXM), and without periodic screening for DSA, were eligible for this study. All enrolled patients were retrospectively tested for DSA using the Luminex assay. The presence of DSA was analyzed in stored serum samples collected at 1 year posttransplantation. If the recipients had DSA, it was analyzed in the pretransplant serum sample. The detection of DSA solely in the 1 year posttransplant sample was defined as dnDSA, and DSA detection in both pretransplant and 1 year posttransplant samples was defined as persistent preformed DSA. RESULTS: DSAs were identified in 14 (8.8%) of the 160 patients. Seven patients had persistent preformed DSA, 6 had dnDSA, and 1 had both persistent preformed and dnDSA at 1 year posttransplantation. Death-censored allograft survival rates of patients with DSA versus those without DSA at 7 and 11 years were 77.9 vs. 97.8% and 60.6 vs. 89.2%, respectively. The graft survival rate was lower in patients with persistent preformed DSA and/or dnDSA. Each case of preformed DSA and dnDSA was associated with long-term graft survival. CONCLUSION: The presence of persistent preformed DSA or dnDSA at 1 year posttransplantation may be a predictor of long-term graft survival. Further study is needed to evaluate whether periodic screening for DSA improves long-term graft survival.

[Kidney transplantation in patients with donor specific antibodies]. / Trasplante renal en pacientes con anticuerpos dirigidos contra donante.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex®, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex® deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex«, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex« deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.(AU)

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex« but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex« should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.(AU)