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01-01-2020 | Kidney Transplantation | Original Article

ABO-incompatible pediatric kidney transplantation without antibody removal

Authors: Takeshi Kawamura, Yuko Hamasaki, Yusuke Takahashi, Junya Hashimoto, Mai Kubota, Masaki Muramatu, Yoshihiro Itabashi, Yoji Hyodo, Yasushi Ohashi, Atushi Aikawa, Ken Sakai, Seiichiro Shishido

Published in: Pediatric Nephrology | Issue 1/2020

Abstract

Background

Because of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal.

Methods

Thirteen pediatric recipients (mean age 7.4, range 3.4–15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day − 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6–18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period.

Results

The mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P < 0.001).

Conclusions

Pre- and post-transplantation antibody removal is not a prerequisite for successful pediatric ABOi LDKT, at least in patients with a low anti-A/B IgG antibody titer. However, LON caused by rituximab should be monitored.

Hattori M, Mieno M, Shishido S et al (2018) Outcomes of pediatric ABO-incompatible living kidney transplantations from 2002 to 2015: an analysis of the Japanese Kidney Transplant Registry. Transplantation 102:1934–1942. https://doi.org/10.1097/tp.0000000000002259 CrossRefPubMed

Shishido S, Hasegawa A (2005) Current status of ABO-incompatible kidney transplantation in children. Pediatr Transplant 9:148–154. https://doi.org/10.1111/j.1399-3046.2004.00234.x CrossRefPubMed

Aikawa A, Kawamura T, Shishido S, Saito K, Takahashi K (2014) ABO-incompatible living-donor pediatric kidney transplantation in Japan. Clinics (Sao Paulo) 69:22–27. https://doi.org/10.6061/clinics/2014sup01)05 CrossRef

Alexandre GP, De Bruyere M, Squifflet JP, Moriau M, Latinne D, Pirson Y (1985) Human ABO-incompatible living donor renal homografts. Neth J Med 28:231–234PubMed

Alexandre GP, Squifflet JP, De Bruyère M et al (1987) Present experiences in a series of 26 ABO-incompatible living donor renal allografts. Transplant Proc 19:4538–4542PubMed

Takahashi K, Saito K, Takahara S et al (2004) Excellent long-term outcome of ABO-incompatible living donor kidney transplantation in Japan. Am J Transplant 4:1089–1096. https://doi.org/10.1111/j.1600-6143.2004.00464.x CrossRefPubMed

Shishido S, Asanuma H, Tajima E et al (2001) ABO-incompatible living-donor kidney transplantation in children. Transplantation 72:1037–1042. https://doi.org/10.1097/00007890-200109270-00010 CrossRefPubMed

Tydén G, Kumlien G, Genberg H et al (2005) ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant 5:145–148. https://doi.org/10.1111/j.1600-6143.2004.00653.x CrossRefPubMed

Gloor JM, Cosio FG, Rea DJ et al (2006) Histologic finding one year after positive crossmatch or ABO blood group incompatible living donor kidney transplantation. Am J Transplant 6:1841–1847. https://doi.org/10.1111/j.1600-6143.2006.01416.x CrossRefPubMed

10.

Fuchinoue S, Ishii Y, Sawada T et al (2011) The 5-year outcome of ABO-incompatible kidney transplantation with rituximab induction. Transplantation 91:853–857. https://doi.org/10.1097/tp.0b013e31820f08e8 CrossRefPubMed

11.

Sugiyama K, Hyodo Y, Aikawa A (2015) Evaluation of blood group antibodies in ABO-incompatible living-donor kidney transplantation. Int J Urol 22:931–936. https://doi.org/10.1111/iju.12845 CrossRefPubMed

12.

Shishido S, Hyodo Y, Aoki Y et al (2012) Transplant outcomes of pediatric ABO-incompatible kidney transplantations are equivalent to ABO-compatible controls. Transplant Proc 44:214–216. https://doi.org/10.1016/j.transproceed.2011.12.017 CrossRefPubMed

13.

Barnett AN, Manook M, Nagendran M et al (2014) Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation. Transpl Int 27:187–196. https://doi.org/10.1111/tri.12234 CrossRefPubMed

14.

Masterson R, Hughes P, Walker RG et al (2014) ABO incompatible renal transplantation without antibody removal using conventional immunosuppression alone. Am J Transplant 14:2807–2813. https://doi.org/10.1111/ajt.12920 CrossRefPubMed

15.

Stojanovic J, Adamusiak A, Kessaris N et al (2017) Immune desensitization allows pediatric blood group incompatible kidney transplantation. Transplantation 101:1242–1246. https://doi.org/10.1097/tp.0000000000001325 CrossRefPubMed

16.

Haas M, Sis B, Racusen LC et al (2014) Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 14:272–283. https://doi.org/10.1111/ajt.12590 CrossRefPubMed

17.

Uemura O, Nagai T, Ishikura K et al (2014) Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol 18:626–633. https://doi.org/10.1007/s10157-013-0856-y CrossRefPubMed

18.

Holdsworth RJ, Irving AD, Cuschieri A (1991) Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. Br J Surg 78:1031–1038. https://doi.org/10.1002/bjs.1800780904 CrossRefPubMed

19.

Davies JM, Lewis MPN, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH, British Committee for Standards in Haematology (2011) Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haematology-Oncology task force. Br J Haematol 155:308–317. https://doi.org/10.1111/j.1365-2141.2011.08843.x CrossRefPubMed

20.

Weledji EP (2014) Benefits and risks of splenectomy. Int J Surg 12:113–119. https://doi.org/10.1016/j.ijsu.2013.11.017 CrossRefPubMed

21.

Gloor JM, Stegall MD (2007) ABO incompatible kidney transplantation. Curr Opin Nephrol Hypertens 16:529–534. https://doi.org/10.1097/MNH.0b013e3282f02218 CrossRefPubMed

22.

Okumi M, Toki D, Nozaki T et al (2016) ABO-incompatible living kidney transplants: evolution of outcomes and immunosuppressive management. Am J Transplant 16:886–896. https://doi.org/10.1111/ajt.13502 CrossRefPubMed

23.

Montgomery RA, Locke JE, King KE et al (2009) ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation 87:1246–1255. https://doi.org/10.1097/tp.0b013e31819f2024 CrossRefPubMed

24.

Takahashi K, Saito K, Nakagawa Y, Tasaki M, Hara N, Imai N (2010) Mechanism of acute antibody-mediated rejection in ABO-incompatible kidney transplantation: which anti-A/anti-B antibodies are responsible, natural or de novo? Transplantation 89:635–637. https://doi.org/10.1097/tp.0b013e3181c89307 CrossRefPubMed

25.

Ishida H, Tanabe K, Furusawa M et al (2004) Efficacy of IgM anti-blood type antibody monitoring by enzyme-linked immunosorbent assay after renal transplantation across the blood barrier: high-dose immunoglobulin administration blocks IgM rather than IgG anti-blood type antibodies. Transplant Proc 36:2178–2181. https://doi.org/10.1016/j.transproceed.2004.08.082 CrossRefPubMed

26.

Schwartz J, Stegall MD, Kremers WK, Gloor J (2006) Complications, resource utilization, and cost of ABO-incompatible living donor kidney transplantation. Transplantation 82:155–163. https://doi.org/10.1097/01.tp.0000226152.13584.ae CrossRefPubMed

27.

Axelrod D, Segev DL, Xiao H et al (2016) Economic impacts of ABO-incompatible live donor kidney transplantation: a national study of medicare-insured recipients. Am J Transplant 16:1465–1473. https://doi.org/10.1111/ajt.13616 CrossRefPubMedPubMedCentral

28.

Toki D, Ishida H, Horita S, Setoguchi K, Yamaguchi Y, Tanabe K (2009) Impact of low-dose rituximab on splenic B cells in ABO-incompatible renal transplant recipients. Transpl Int 22:447–454. https://doi.org/10.1111/j.1432-2277.2008.00821.x CrossRefPubMed

29.

Wolach O, Bairey O, Lahav M (2010) Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine (Baltimore) 89:308–318. https://doi.org/10.1097/md.0b013e3181f2caef CrossRef

30.

Ishida H, Inui M, Furusawa M, Tanabe K (2013) Late-onset neutropenia (LON) after low-dose rituximab treatment in living related kidney transplantation--single-center study. Transpl Immunol 28:93–99. https://doi.org/10.1097/00007890-201407151-00202 CrossRefPubMed

31.

Shirakawa H, Ishida H, Shimizu T, Omoto K, Iida S, Toki D, Tanabe K (2011) The low dose of rituximab in ABO-incompatible kidney transplantation without a splenectomy: a single-center experience. Clin Transpl 25:878–884. https://doi.org/10.1111/j.1399-0012.2010.01384.x CrossRef

Title: ABO-incompatible pediatric kidney transplantation without antibody removal
Authors: Takeshi Kawamura
Yuko Hamasaki
Yusuke Takahashi
Junya Hashimoto
Mai Kubota
Masaki Muramatu
Yoshihiro Itabashi
Yoji Hyodo
Yasushi Ohashi
Atushi Aikawa
Ken Sakai
Seiichiro Shishido
Publication date: 01-01-2020
Publisher: Springer Berlin Heidelberg
Keywords: Kidney Transplantation
Splenectomy
Splenectomy
Rituximab
Kidney Transplantation
Kidney Transplantation
Neutropenia
Kidney Transplantation
Kidney Transplantation
Kidney Transplantation
Rituximab
Mycophenolate Mofetil
Calcineurin Inhibitors
Published in: Pediatric Nephrology / Issue 1/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-019-04376-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

ABO-incompatible pediatric kidney transplantation without antibody removal

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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