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Erschienen in: Pediatric Nephrology 10/2016

22.01.2016 | Original Article

Management of sensitized pediatric patients prior to renal transplantation

verfasst von: Kwanchai Pirojsakul, Dev Desai, M.D., Chantale Lacelle, Mouin G. Seikaly

Erschienen in: Pediatric Nephrology | Ausgabe 10/2016

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Abstract

Background

Data on renal allograft outcome in sensitized children are scarce. We report the clinical courses of four children who received desensitization therapy prior to renal transplantation in our institution.

Methods

Between 2009 and 2011, four pediatric patients with stage 5 chronic kidney disease received desensitization therapy due to: (1) positive donor-specific antibodies (DSA) and/or crossmatches with potential living donors, (2) more than three positive crossmatches with deceased donors or (3) high calculated panel-reactive antibody of >80 %. Desensitization with rituximab, intravenous immunoglobulin and bortezomib was performed in all patients. Induction therapy included combinations of plasmapheresis and/or alemtuzumab or anti-thymocyte globulin. Standard post-transplant medications included tacrolimus, mycophenolate mofetil and prednisolone.

Results

Post-transplant screening revealed DSA in three patients. Biopsy showed no evidence of rejection at 1 month in two patients, one of whom developed chronic active antibody-mediated rejection 4.5 years later. One patient developed borderline acute cellular rejection at 1 month, but the serum creatinine level was stable and DSA disappeared without treatment 1 month later, with stable long-term allograft function at 3 years. Estimated or measured glomerular filtration rate of the patients ranged between 30 and 75 ml/min/1.73 m2 after 1 to 4.5 years.

Conclusions

The four sensitized patients reported here who received desensitization therapy had successful renal transplants with a low risk of immediate post-transplant rejection. Overall, long-term allograft functions and complications from immunosuppression were encouraging.
Literatur
1.
Zurück zum Zitat Shapiro R, Sarwal MM (2010) Pediatric kidney transplantation. Pediatr Clin North Am 57:393–400CrossRefPubMed Shapiro R, Sarwal MM (2010) Pediatric kidney transplantation. Pediatr Clin North Am 57:393–400CrossRefPubMed
2.
Zurück zum Zitat Lee KW, Kim SJ, Lee DS, Lee HH, Joh JW, Lee SK, Oh HY, Kim DJ, Kim YG, Huh WS, Oh WI, Lee BB (2004) Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation. Transplant Proc 36:2009–2010CrossRefPubMed Lee KW, Kim SJ, Lee DS, Lee HH, Joh JW, Lee SK, Oh HY, Kim DJ, Kim YG, Huh WS, Oh WI, Lee BB (2004) Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation. Transplant Proc 36:2009–2010CrossRefPubMed
3.
Zurück zum Zitat Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, Warren DS, Simpkins CE, Dagher NN, Singer AL, Zachary AA, Segev DL (2011) Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 365:318–326CrossRefPubMed Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, Warren DS, Simpkins CE, Dagher NN, Singer AL, Zachary AA, Segev DL (2011) Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 365:318–326CrossRefPubMed
4.
Zurück zum Zitat Marfo K, Lu A, Ling M, Akalin E (2011) Desensitization protocols and their outcome. Clin J Am Soc Nephrol 6:922–936CrossRefPubMed Marfo K, Lu A, Ling M, Akalin E (2011) Desensitization protocols and their outcome. Clin J Am Soc Nephrol 6:922–936CrossRefPubMed
5.
Zurück zum Zitat Valentini RP, Nehlsen-Cannarella SL, Gruber SA, Mattoo TK, West MS, Lang C, Imam AA (2007) Intravenous immunoglobulin, HLA allele typing and HLAMatchmaker facilitate successful transplantation in highly sensitized pediatric renal allograft recipients. Pediatr Transplant 11:77–81CrossRefPubMed Valentini RP, Nehlsen-Cannarella SL, Gruber SA, Mattoo TK, West MS, Lang C, Imam AA (2007) Intravenous immunoglobulin, HLA allele typing and HLAMatchmaker facilitate successful transplantation in highly sensitized pediatric renal allograft recipients. Pediatr Transplant 11:77–81CrossRefPubMed
6.
Zurück zum Zitat Quinlan C, Awan A, Gill D, Waldron M, Little D, Hickey D, Conlon P, Keogan M (2011) Pediatric renal transplantation in a highly sensitised child-8 years on. Case Rep Transplant 2011:370596PubMed Quinlan C, Awan A, Gill D, Waldron M, Little D, Hickey D, Conlon P, Keogan M (2011) Pediatric renal transplantation in a highly sensitised child-8 years on. Case Rep Transplant 2011:370596PubMed
7.
Zurück zum Zitat Pradhan M, Raffaelli RM, Lind C, Meyers KE, Kaplan BS, Baluarte HJ, Monos D (2008) Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis. Pediatr Transplant 12:711–716CrossRefPubMed Pradhan M, Raffaelli RM, Lind C, Meyers KE, Kaplan BS, Baluarte HJ, Monos D (2008) Successful deceased donor renal transplant in a sensitized pediatric recipient with the use of plasmapheresis. Pediatr Transplant 12:711–716CrossRefPubMed
8.
Zurück zum Zitat Al-Uzri AY, Seltz B, Yorgin PD, Spier CM, Andreoni K (2002) Successful renal transplant outcome after intravenous gamma-globulin treatment of a highly sensitized pediatric recipient. Pediatr Transplant 6:161–165CrossRefPubMed Al-Uzri AY, Seltz B, Yorgin PD, Spier CM, Andreoni K (2002) Successful renal transplant outcome after intravenous gamma-globulin treatment of a highly sensitized pediatric recipient. Pediatr Transplant 6:161–165CrossRefPubMed
9.
Zurück zum Zitat Tyan DB, Li VA, Czer L, Trento A, Jordan SC (1994) Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 57:553–562CrossRefPubMed Tyan DB, Li VA, Czer L, Trento A, Jordan SC (1994) Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 57:553–562CrossRefPubMed
10.
Zurück zum Zitat Narayan S, Tsai EW, Zhang Q, Wallace WD, Reed EF, Ettenger RB (2011) Acute rejection associated with donor-specific anti-MICA antibody in a highly sensitized pediatric renal transplant recipient. Pediatr Transplant 15:E1–7CrossRefPubMed Narayan S, Tsai EW, Zhang Q, Wallace WD, Reed EF, Ettenger RB (2011) Acute rejection associated with donor-specific anti-MICA antibody in a highly sensitized pediatric renal transplant recipient. Pediatr Transplant 15:E1–7CrossRefPubMed
11.
Zurück zum Zitat Miura M, Kubota KC, Itoh T, Ono T, Morita K, Watarai Y, Harada H, Hirano T, Nonomura K (2006) Positive pre-transplant flow-panel reactive antibody detected after accelerated acute rejection with negative pre-transplant flow crossmatch. Clin Transplant 20(Suppl 15):33–37CrossRefPubMed Miura M, Kubota KC, Itoh T, Ono T, Morita K, Watarai Y, Harada H, Hirano T, Nonomura K (2006) Positive pre-transplant flow-panel reactive antibody detected after accelerated acute rejection with negative pre-transplant flow crossmatch. Clin Transplant 20(Suppl 15):33–37CrossRefPubMed
12.
Zurück zum Zitat Siddique K, Leonard D, Borders L, Seikaly MG (2014) Validation of the CKiD formulae to estimate GFR in children post renal transplant. Pediatr Nephrol 29:445–451CrossRefPubMed Siddique K, Leonard D, Borders L, Seikaly MG (2014) Validation of the CKiD formulae to estimate GFR in children post renal transplant. Pediatr Nephrol 29:445–451CrossRefPubMed
13.
Zurück zum Zitat Krumbholz M, Derfuss T, Hohlfeld R, Meinl E (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613–623CrossRefPubMed Krumbholz M, Derfuss T, Hohlfeld R, Meinl E (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613–623CrossRefPubMed
14.
Zurück zum Zitat Budde K, Lehner LJ (2015) Bortezomib-based antibody reduction therapy: the first step to "true" desensitization? Am J Transplant 15:10–12CrossRefPubMed Budde K, Lehner LJ (2015) Bortezomib-based antibody reduction therapy: the first step to "true" desensitization? Am J Transplant 15:10–12CrossRefPubMed
15.
Zurück zum Zitat Nguyen S, Gallay B, Butani L (2014) Efficacy of bortezomib for reducing donor-specific antibodies in children and adolescents on a steroid minimization regimen. Pediatr Transplant 18:463–468CrossRefPubMed Nguyen S, Gallay B, Butani L (2014) Efficacy of bortezomib for reducing donor-specific antibodies in children and adolescents on a steroid minimization regimen. Pediatr Transplant 18:463–468CrossRefPubMed
16.
Zurück zum Zitat Twombley K, Thach L, Ribeiro A, Joseph C, Seikaly M (2013) Acute antibody-mediated rejection in pediatric kidney transplants: a single center experience. Pediatr Transplant 17:E149–155CrossRefPubMed Twombley K, Thach L, Ribeiro A, Joseph C, Seikaly M (2013) Acute antibody-mediated rejection in pediatric kidney transplants: a single center experience. Pediatr Transplant 17:E149–155CrossRefPubMed
17.
Zurück zum Zitat Ryckewaert A, Allain-Launay E, Moreau A, Blancho G, Cesbron A, Blin N, Roussey G (2013) Failure of bortezomib to cure acute antibody-mediated rejection in a non-compliant renal transplant patient. Pediatr Transplant 17:E131–136CrossRefPubMed Ryckewaert A, Allain-Launay E, Moreau A, Blancho G, Cesbron A, Blin N, Roussey G (2013) Failure of bortezomib to cure acute antibody-mediated rejection in a non-compliant renal transplant patient. Pediatr Transplant 17:E131–136CrossRefPubMed
18.
Zurück zum Zitat Westphal S, Hansson S, Stelin G, Holgersson J, Mjornstedt L, Friman S (2013) Successful treatment of severe ABO antibody-mediated rejection using bortezomib: a case report. Transplant Proc 45:1213–1215CrossRefPubMed Westphal S, Hansson S, Stelin G, Holgersson J, Mjornstedt L, Friman S (2013) Successful treatment of severe ABO antibody-mediated rejection using bortezomib: a case report. Transplant Proc 45:1213–1215CrossRefPubMed
19.
Zurück zum Zitat May LJ, Yeh J, Maeda K, Tyan DB, Chen S, Kaufman BD, Bernstein D, Rosenthal DN, Hollander SA (2014) HLA desensitization with bortezomib in a highly sensitized pediatric patient. Pediatr Transplant 18:E280–282CrossRefPubMed May LJ, Yeh J, Maeda K, Tyan DB, Chen S, Kaufman BD, Bernstein D, Rosenthal DN, Hollander SA (2014) HLA desensitization with bortezomib in a highly sensitized pediatric patient. Pediatr Transplant 18:E280–282CrossRefPubMed
21.
Zurück zum Zitat Watanabe J, Scornik JC (2005) IVIG and HLA antibodies Evidence for inhibition of complement activation but not for anti-idiotypic activity. Am J Transplant 5:2786–2790CrossRefPubMed Watanabe J, Scornik JC (2005) IVIG and HLA antibodies Evidence for inhibition of complement activation but not for anti-idiotypic activity. Am J Transplant 5:2786–2790CrossRefPubMed
22.
Zurück zum Zitat Samuelsson A, Towers TL, Ravetch JV (2001) Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291:484–486CrossRefPubMed Samuelsson A, Towers TL, Ravetch JV (2001) Anti-inflammatory activity of IVIG mediated through the inhibitory Fc receptor. Science 291:484–486CrossRefPubMed
23.
Zurück zum Zitat Jordan SC, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D (2003) Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation 76:631–636CrossRefPubMed Jordan SC, Vo A, Bunnapradist S, Toyoda M, Peng A, Puliyanda D, Kamil E, Tyan D (2003) Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation 76:631–636CrossRefPubMed
24.
Zurück zum Zitat Akalin E, Dinavahi R, Friedlander R, Ames S, de Boccardo G, Sehgal V, Schröppel B, Bhaskaran M, Lerner S, Fotino M, Murphy B, Bromberg JS (2008) Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sensitized patients with strong donor-specific antibodies. Clin J Am Soc Nephrol 3:1160–1167CrossRefPubMedPubMedCentral Akalin E, Dinavahi R, Friedlander R, Ames S, de Boccardo G, Sehgal V, Schröppel B, Bhaskaran M, Lerner S, Fotino M, Murphy B, Bromberg JS (2008) Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sensitized patients with strong donor-specific antibodies. Clin J Am Soc Nephrol 3:1160–1167CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Mai ML, Ahsan N, Wadei HM, Genco PV, Geiger XJ, Willingham DL, Taner CB, Hewitt WR, Grewal HP, Nguyen JH, Hughes CB, Gonwa TA (2009) Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin. Transplantation 87:227–232CrossRefPubMed Mai ML, Ahsan N, Wadei HM, Genco PV, Geiger XJ, Willingham DL, Taner CB, Hewitt WR, Grewal HP, Nguyen JH, Hughes CB, Gonwa TA (2009) Excellent renal allograft survival in donor-specific antibody positive transplant patients-role of intravenous immunoglobulin and rabbit antithymocyte globulin. Transplantation 87:227–232CrossRefPubMed
26.
Zurück zum Zitat Jackson AM, Kraus ES, Orandi BJ, Segev DL, Montgomery RA, Zachary AA (2015) A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation. Kidney Int 87:409–416CrossRefPubMed Jackson AM, Kraus ES, Orandi BJ, Segev DL, Montgomery RA, Zachary AA (2015) A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation. Kidney Int 87:409–416CrossRefPubMed
27.
Zurück zum Zitat Jordan SC, Choi J, Vo A (2015) Kidney transplantation in highly sensitized patients. Br Med Bull 114:113–125CrossRefPubMed Jordan SC, Choi J, Vo A (2015) Kidney transplantation in highly sensitized patients. Br Med Bull 114:113–125CrossRefPubMed
28.
Zurück zum Zitat Grafft CA, Cornell LD, Gloor JM, Cosio FG, Gandhi MJ, Dean PG, Stegall MD, Amer H (2010) Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol Dial Transplant 25:307–310CrossRefPubMed Grafft CA, Cornell LD, Gloor JM, Cosio FG, Gandhi MJ, Dean PG, Stegall MD, Amer H (2010) Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrol Dial Transplant 25:307–310CrossRefPubMed
29.
Zurück zum Zitat Zou Y, Stastny P, Susal C, Dohler B, Opelz G (2007) Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med 357:1293–1300CrossRefPubMed Zou Y, Stastny P, Susal C, Dohler B, Opelz G (2007) Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med 357:1293–1300CrossRefPubMed
Metadaten
Titel
Management of sensitized pediatric patients prior to renal transplantation
verfasst von
Kwanchai Pirojsakul
Dev Desai, M.D.
Chantale Lacelle
Mouin G. Seikaly
Publikationsdatum
22.01.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 10/2016
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-015-3295-z

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