Renal transplantation in sensitized children and young adults: A nationwide approach

Luca Dello Strologo, Luisa Murer, Isabella Guzzo, Federica Morolli, Annalisa Maria Valeria Pipicelli, Elisa Benetti, Germana Longo, Sara Testa, A. Ricci, Fabrizio Ginevri, Luciana Ghio, Massimo Cardillo, Antonina Piazza, Alessandro Nanni Costa

Research output: Contribution to journalArticle

Abstract

Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P <0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.
Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalNephrology Dialysis Transplantation
Volume32
Issue number1
DOIs
Publication statusPublished - 2017

Fingerprint

Kidney Transplantation
Young Adult
Waiting Lists
Transplants
Kidney
Transplantation
Life Expectancy
Italy
Anti-Idiotypic Antibodies
Creatinine
Tissue Donors
Pediatrics
Antigens
Antibodies

Keywords

  • Allocation policy
  • Paediatric
  • Renal transplant
  • Sensitization
  • alloantibody
  • panel reactive antibody
  • HLA antigen
  • adult
  • Article
  • blood group typing
  • child
  • clinical article
  • cohort analysis
  • controlled study
  • creatinine clearance
  • follow up
  • health program
  • hospital admission
  • human
  • Italy
  • kidney graft
  • kidney graft rejection
  • kidney transplantation
  • organ donor
  • protein analysis
  • sensitization
  • young adult
  • adolescent
  • blood
  • chronic kidney failure
  • desensitization
  • female
  • graft survival
  • histocompatibility test
  • immunology
  • male
  • preschool child
  • procedures
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Desensitization, Immunologic
  • Female
  • Graft Survival
  • Histocompatibility Testing
  • HLA Antigens
  • Humans
  • Isoantibodies
  • Kidney Failure, Chronic
  • Kidney Transplantation
  • Male
  • Young Adult

Cite this

Dello Strologo, L., Murer, L., Guzzo, I., Morolli, F., Pipicelli, A. M. V., Benetti, E., ... Costa, A. N. (2017). Renal transplantation in sensitized children and young adults: A nationwide approach. Nephrology Dialysis Transplantation, 32(1), 191-195. https://doi.org/10.1093/ndt/gfw369

Renal transplantation in sensitized children and young adults: A nationwide approach. / Dello Strologo, Luca; Murer, Luisa; Guzzo, Isabella; Morolli, Federica; Pipicelli, Annalisa Maria Valeria; Benetti, Elisa; Longo, Germana; Testa, Sara; Ricci, A.; Ginevri, Fabrizio; Ghio, Luciana; Cardillo, Massimo; Piazza, Antonina; Costa, Alessandro Nanni.

In: Nephrology Dialysis Transplantation, Vol. 32, No. 1, 2017, p. 191-195.

Research output: Contribution to journalArticle

Dello Strologo, L, Murer, L, Guzzo, I, Morolli, F, Pipicelli, AMV, Benetti, E, Longo, G, Testa, S, Ricci, A, Ginevri, F, Ghio, L, Cardillo, M, Piazza, A & Costa, AN 2017, 'Renal transplantation in sensitized children and young adults: A nationwide approach', Nephrology Dialysis Transplantation, vol. 32, no. 1, pp. 191-195. https://doi.org/10.1093/ndt/gfw369
Dello Strologo L, Murer L, Guzzo I, Morolli F, Pipicelli AMV, Benetti E et al. Renal transplantation in sensitized children and young adults: A nationwide approach. Nephrology Dialysis Transplantation. 2017;32(1):191-195. https://doi.org/10.1093/ndt/gfw369
Dello Strologo, Luca ; Murer, Luisa ; Guzzo, Isabella ; Morolli, Federica ; Pipicelli, Annalisa Maria Valeria ; Benetti, Elisa ; Longo, Germana ; Testa, Sara ; Ricci, A. ; Ginevri, Fabrizio ; Ghio, Luciana ; Cardillo, Massimo ; Piazza, Antonina ; Costa, Alessandro Nanni. / Renal transplantation in sensitized children and young adults: A nationwide approach. In: Nephrology Dialysis Transplantation. 2017 ; Vol. 32, No. 1. pp. 191-195.
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abstract = "Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80{\%}. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P <0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.",
keywords = "Allocation policy, Paediatric, Renal transplant, Sensitization, alloantibody, panel reactive antibody, HLA antigen, adult, Article, blood group typing, child, clinical article, cohort analysis, controlled study, creatinine clearance, follow up, health program, hospital admission, human, Italy, kidney graft, kidney graft rejection, kidney transplantation, organ donor, protein analysis, sensitization, young adult, adolescent, blood, chronic kidney failure, desensitization, female, graft survival, histocompatibility test, immunology, male, preschool child, procedures, Adolescent, Adult, Child, Child, Preschool, Desensitization, Immunologic, Female, Graft Survival, Histocompatibility Testing, HLA Antigens, Humans, Isoantibodies, Kidney Failure, Chronic, Kidney Transplantation, Male, Young Adult",
author = "{Dello Strologo}, Luca and Luisa Murer and Isabella Guzzo and Federica Morolli and Pipicelli, {Annalisa Maria Valeria} and Elisa Benetti and Germana Longo and Sara Testa and A. Ricci and Fabrizio Ginevri and Luciana Ghio and Massimo Cardillo and Antonina Piazza and Costa, {Alessandro Nanni}",
note = "Export Date: 12 April 2018 CODEN: NDTRE Correspondence Address: Strologo, L.D.; Nephrology and Transplant Unit, Bambino Gesu Children's Hospital, IRCCSItaly; email: luca.dellostrologo@opbg.net Chemicals/CAS: HLA Antigens; Isoantibodies References: Jordan, S.C., Pescovitz, M.D., Presensitization: The problem and its management (2006) Clin J Am Soc Nephrol, 1, pp. 421-432; Gloor, J., Stegall, M.D., Sensitized renal transplant recipients: Current protocols and future directions (2010) Nat Rev Nephrol, 6, pp. 297-306; Haririan, A., Nogueira, J., Kukuruga, D., Positive cross-match living donor kidney transplantation: Longer-term outcomes (2009) Am J Transplant, 9, pp. 536-542; Mao, Q., Terasaki, P.I., Cai, J., Extremely high association between appearance of HLA antibodies and failure of kidney grafts in a five-year longitudinal study (2007) Am J Transplant, 7, pp. 864-871; Finnegan-John, J., Thomas, V.J., The psychosocial experience of patients with end-stage renal disease and its impact on quality of life: Findings from a needs assessment to shape a service (2013) ISRN Nephrol, 2013, p. 308986; Cukor, D., Cohen, S.D., Peterson, R.A., Psychosocial aspects of chronic disease: ESRD as a paradigmatic illness (2007) J Am Soc Nephrol, 18, pp. 3042-3055; Kimmel, P.L., Cukor, D., Cohen, S.D., Depression in end-stage renal disease patients: A critical review (2007) Adv Chronic Kidney Dis, 14, pp. 328-334; Jassal, S.V., Karaboyas, A., Comment, L.A., Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS) (2016) Am J Kidney Dis, 67, pp. 283-292; Vo, A.A., Choi, J., Kim, I., A phase I/II trial of the interleukin-6 receptor specific humanized monoclonal (tocilizumab) + intravenous immunoglobulin in difficult to desensitize patients (2015) Transplantation, 99, pp. 2356-2363; Vo, A.A., Choi, J., Cisneros, K., Benefits of rituximab combined with intravenous immunoglobulin for desensitization in kidney transplant recipients (2014) Transplantation, 98, pp. 312-319; Vo, A.A., Lukovsky, M., Toyoda, M., Rituximab and intravenous immune globulin for desensitization during renal transplantation (2008) N Engl J Med, 359, pp. 242-251; Stegall, M.D., Diwan, T., Raghavaiah, S., Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients (2011) Am J Transplant, 11, pp. 2405-2413; Cornell, L.D., Schinstock, C.A., Gandhi, M.J., Positive crossmatch kidney transplant recipients treated with eculizumab: Outcomes beyond 1 year (2015) Am J Transplant, 15, pp. 1293-1302; Claas, F.H., Witvliet, M.D., Duquesnoy, R.J., The acceptable mismatch program as a fast tool for highly sensitized patients awaiting a cadaveric kidney transplantation: Short waiting time and excellent graft outcome (2004) Transplantation, 78, pp. 190-193; Heidt, S., Witvliet, M.D., Haasnoot, G.W., The 25th anniversary of the Eurotransplant AcceptableMismatch programfor highly sensitized patients (2015) Transpl Immunol, 33, pp. 51-57; Nguyen, H.D., Wong, G., Howard, K., Modeling the benefits and costs of integrating an acceptable HLA mismatch allocation model for highly sensitized patients (2014) Transplantation, 97, pp. 769-774",
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doi = "10.1093/ndt/gfw369",
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TY - JOUR

T1 - Renal transplantation in sensitized children and young adults: A nationwide approach

AU - Dello Strologo, Luca

AU - Murer, Luisa

AU - Guzzo, Isabella

AU - Morolli, Federica

AU - Pipicelli, Annalisa Maria Valeria

AU - Benetti, Elisa

AU - Longo, Germana

AU - Testa, Sara

AU - Ricci, A.

AU - Ginevri, Fabrizio

AU - Ghio, Luciana

AU - Cardillo, Massimo

AU - Piazza, Antonina

AU - Costa, Alessandro Nanni

N1 - Export Date: 12 April 2018 CODEN: NDTRE Correspondence Address: Strologo, L.D.; Nephrology and Transplant Unit, Bambino Gesu Children's Hospital, IRCCSItaly; email: luca.dellostrologo@opbg.net Chemicals/CAS: HLA Antigens; Isoantibodies References: Jordan, S.C., Pescovitz, M.D., Presensitization: The problem and its management (2006) Clin J Am Soc Nephrol, 1, pp. 421-432; Gloor, J., Stegall, M.D., Sensitized renal transplant recipients: Current protocols and future directions (2010) Nat Rev Nephrol, 6, pp. 297-306; Haririan, A., Nogueira, J., Kukuruga, D., Positive cross-match living donor kidney transplantation: Longer-term outcomes (2009) Am J Transplant, 9, pp. 536-542; Mao, Q., Terasaki, P.I., Cai, J., Extremely high association between appearance of HLA antibodies and failure of kidney grafts in a five-year longitudinal study (2007) Am J Transplant, 7, pp. 864-871; Finnegan-John, J., Thomas, V.J., The psychosocial experience of patients with end-stage renal disease and its impact on quality of life: Findings from a needs assessment to shape a service (2013) ISRN Nephrol, 2013, p. 308986; Cukor, D., Cohen, S.D., Peterson, R.A., Psychosocial aspects of chronic disease: ESRD as a paradigmatic illness (2007) J Am Soc Nephrol, 18, pp. 3042-3055; Kimmel, P.L., Cukor, D., Cohen, S.D., Depression in end-stage renal disease patients: A critical review (2007) Adv Chronic Kidney Dis, 14, pp. 328-334; Jassal, S.V., Karaboyas, A., Comment, L.A., Functional Dependence and Mortality in the International Dialysis Outcomes and Practice Patterns Study (DOPPS) (2016) Am J Kidney Dis, 67, pp. 283-292; Vo, A.A., Choi, J., Kim, I., A phase I/II trial of the interleukin-6 receptor specific humanized monoclonal (tocilizumab) + intravenous immunoglobulin in difficult to desensitize patients (2015) Transplantation, 99, pp. 2356-2363; Vo, A.A., Choi, J., Cisneros, K., Benefits of rituximab combined with intravenous immunoglobulin for desensitization in kidney transplant recipients (2014) Transplantation, 98, pp. 312-319; Vo, A.A., Lukovsky, M., Toyoda, M., Rituximab and intravenous immune globulin for desensitization during renal transplantation (2008) N Engl J Med, 359, pp. 242-251; Stegall, M.D., Diwan, T., Raghavaiah, S., Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients (2011) Am J Transplant, 11, pp. 2405-2413; Cornell, L.D., Schinstock, C.A., Gandhi, M.J., Positive crossmatch kidney transplant recipients treated with eculizumab: Outcomes beyond 1 year (2015) Am J Transplant, 15, pp. 1293-1302; Claas, F.H., Witvliet, M.D., Duquesnoy, R.J., The acceptable mismatch program as a fast tool for highly sensitized patients awaiting a cadaveric kidney transplantation: Short waiting time and excellent graft outcome (2004) Transplantation, 78, pp. 190-193; Heidt, S., Witvliet, M.D., Haasnoot, G.W., The 25th anniversary of the Eurotransplant AcceptableMismatch programfor highly sensitized patients (2015) Transpl Immunol, 33, pp. 51-57; Nguyen, H.D., Wong, G., Howard, K., Modeling the benefits and costs of integrating an acceptable HLA mismatch allocation model for highly sensitized patients (2014) Transplantation, 97, pp. 769-774

PY - 2017

Y1 - 2017

N2 - Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P <0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.

AB - Background. High levels of preformed anti-HLA antibodies dramatically diminish renal transplant outcomes.Most desensitization programmes guarantee good intermediate outcomes but quite disappointing long-term prognosis. The search for a fully compatible kidney increases time on the waiting list. Methods. In February 2011, a nationwide hyperimmune programme (NHP) was begun in Italy: all available kidneys are primarily proposed to highly sensitized patients with a panel reactive antibody above 80%. In this manuscript, we evaluate the outcome of paediatric patients transplanted with this approach. Results. Twenty-one patients were transplanted. Complete data are available for 20 patients. Mean age at transplantation was 14.5 years [standard deviation (SD) 6 5.5)]. Mean time on the waiting list was 29.3 months (SD 6 27.5). Median follow-up was 29.2 months (range: 11.2-59.3). The average number of HLA mismatches in these patients was 2.3 versus 3.7 in 48 standard patients transplanted in the same period (P <0.001). Only one graft was lost. Two cases of humoral rejection occurred and were successfully treated. No cellular rejection was reported. Median creatinine clearance was 84, 88, 77 and 77 mL/min/1.73 m2 respectively 1, 6, 12 and 24 months after transplant. Conclusions. Transplantation of sensitized patients avoiding prohibited antigens is feasible, at least in a selected cohort of patients. In order to be able to further improve this approach, which in our opinion is very successful, it would be necessary to expand the donor pool, possibly increasing the number of countries participating in the programme. In this series, time on the waiting list did not increase significantly. This allocation policy should ideally lead to an outcome comparable to that expected in standard patients, which is particularly desirable in young patients who have the longest life expectancy. Since long-term results of desensitization programmes are not (yet) convincing, we suggest that these programmes should be reserved for selected cases where compatible organs cannot be found within a reasonable time span.

KW - Allocation policy

KW - Paediatric

KW - Renal transplant

KW - Sensitization

KW - alloantibody

KW - panel reactive antibody

KW - HLA antigen

KW - adult

KW - Article

KW - blood group typing

KW - child

KW - clinical article

KW - cohort analysis

KW - controlled study

KW - creatinine clearance

KW - follow up

KW - health program

KW - hospital admission

KW - human

KW - Italy

KW - kidney graft

KW - kidney graft rejection

KW - kidney transplantation

KW - organ donor

KW - protein analysis

KW - sensitization

KW - young adult

KW - adolescent

KW - blood

KW - chronic kidney failure

KW - desensitization

KW - female

KW - graft survival

KW - histocompatibility test

KW - immunology

KW - male

KW - preschool child

KW - procedures

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Desensitization, Immunologic

KW - Female

KW - Graft Survival

KW - Histocompatibility Testing

KW - HLA Antigens

KW - Humans

KW - Isoantibodies

KW - Kidney Failure, Chronic

KW - Kidney Transplantation

KW - Male

KW - Young Adult

U2 - 10.1093/ndt/gfw369

DO - 10.1093/ndt/gfw369

M3 - Article

VL - 32

SP - 191

EP - 195

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 1

ER -