Rapid reduction of high-level pre-formed donor-specific antibodies after simultaneous liver-kidney transplantation: a report of two cases.
Allograft rejection
CDC
Case report
Complement-dependent cytotoxic
DSA
Desensitisation
Donor-specific antibodies
SLKT
Simultaneous liver-kidney transplantation
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
12 02 2020
12 02 2020
Historique:
received:
26
11
2019
accepted:
07
02
2020
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
3
7
2021
Statut:
epublish
Résumé
Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required. Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant. These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.
Sections du résumé
BACKGROUND
Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required.
CASE PRESENTATION
Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant.
CONCLUSIONS
These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.
Identifiants
pubmed: 32050922
doi: 10.1186/s12882-020-01714-y
pii: 10.1186/s12882-020-01714-y
pmc: PMC7014704
doi:
Substances chimiques
HLA Antigens
0
Immunosuppressive Agents
0
Isoantibodies
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Références
Clin Transplant. 2018 May;32(5):e13244
pubmed: 29577436
Transpl Int. 2019 Apr;32(4):343-352
pubmed: 30548094
Transplant Proc. 1997 Nov;29(7):3164-5
pubmed: 9365711
Am J Transplant. 2012 Jun;12(6):1504-10
pubmed: 22420671
Liver Transpl Surg. 1998 Sep;4(5):363-9
pubmed: 9724473
Am J Transplant. 2003 Mar;3(3):348-56
pubmed: 12614293
Kidney Int. 2017 May;91(5):1193-1202
pubmed: 28233612
Transplant Direct. 2016 Nov 23;2(12):e121
pubmed: 27990486
Transplantation. 2013 Nov 27;96(10):914-8
pubmed: 23903012
Transplant Proc. 2017 Jul - Aug;49(6):1394-1401
pubmed: 28736013
Am J Transplant. 2011 Apr;11(4):841-7
pubmed: 21446981
Clin Exp Immunol. 1990 Jun;80(3):404-8
pubmed: 2372988
Transplantation. 2020 Aug;104(8):1591-1603
pubmed: 32732836
Liver Transpl. 2018 Feb;24(2):222-232
pubmed: 28926173
Kidney Int. 2016 Apr;89(4):909-17
pubmed: 26924059
Transplant Proc. 2006 May;38(4):1125-6
pubmed: 16757284
Am J Transplant. 2013 Apr;13(4):954-960
pubmed: 23433356