Desensitization protocol enabling pediatric crossmatch-positive renal transplantation: successful HLA-antibody-incompatible renal transplantation of two highly sensitized children

Abstract

BackgroundRenal transplantation improves quality of life (QoL) and survival in children requiring renal replacement therapy (RRT). Sensitization with development of a broad-spectrum of anti-HLA antibodies as a result of previous transplantation or after receiving blood products is an increasing problem. There are no published reports of desensitization protocols in children allowing renal transplantation from HLA-antibody-incompatible living donors.MethodsWe adopted our well-established adult desensitization protocol for this purpose and undertook HLA antibody-incompatible living donor renal transplants in two children: a 14-year-old girl and a 13-year-old boy.ResultsAfter 2 and 1.5 years of follow-up, respectively, both patients have stable renal allograft function despite a rise in donor-specific antibodies in one case.ConclusionsHLA-incompatible transplantation should be considered in selected cases for sensitized children.

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report

“…73 Moreover, the efficacy of desensitization has been measured in multiple ways, including the rate of transplantation, change in MFI, decrease in number of unacceptable antigens, converting a crossmatch from positive to negative, and changes in cPRA. [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] Some of these variables were assessed as dichotomous parameters, for example, crossmatch positive or negative rather than quantifying changes in the positivity strength. Indeed, converting a complement-dependent cytotoxicity-positive crossmatch to only flow cytometry-positive crossmatch captures some of this information, yet the nuances that are captured by this change are very limited.…”

Successful ABO and HLA incompatible kidney transplantation in children in the UK

“…With the shortage of deceased donor kidneys and sensitisation of children due to blood transfusions and previous transplants, ABOi and HLAi kidney transplantation has been performed more often in the last few decades [ 13 , 14 , 23 , 24 ]. There is increasing evidence in the literature that kidney transplantation offers significant survival advantages compared to remaining on dialysis [ 4 , 25 ].…”

“…In the UK, a national living donor kidney sharing scheme exists and incompatible pairs are advised to enter the scheme. Ideally, there would be a trial of at least three quarterly runs although successful matching runs are less likely in highly sensitised children [ 13 ]. For highly sensitised patients, positive cross-matched transplantation after appropriate desensitisation may lead to better patient survival than staying on dialysis [ 3 , 11 , 29 ].…”

“…The field of paediatric kidney transplantation has made major advances over the last five decades [5], with marked improvements in patient and kidney allograft survival in recent years [4,6]. While ABO and HLA compatible kidney transplantation is still preferred, increasing shortage of deceased donor kidneys [7] and sensitisation of children due to blood transfusions and previous transplants [8][9][10] have resulted in strategies with antibody removal to permit ABO incompatible (ABOi) and HLA incompatible (HLAi) kidney transplantation in children [3,[11][12][13][14]. Although there are encouraging and extensive data for adult KTR [15], many centres have been slow to incorporate this method of transplantation into paediatric programmes for several reasons.…”

Kidney transplantation outcomes for adult recipients of pediatric donor kidneys

“…Data were available for a range of donor, recipient, and transplant‐related factors. Of those relating to donor‐recipient matching, the calculated HLA antibody reaction frequency (cRF) defines the level of sensitization and is derived from the proportion of the last 10,000 deceased donors exhibiting HLA antigens that react with a patient's serum 11 . In addition, the number of HLA mismatches was assessed, and grouped into four levels, as follows: Level 1 [000]: 000 Level 2 [0 DR and 0/1 B]: 100, 010, 110, 200, 210 Level 3 [0 DR and 2 B] or [1 DR and 0/1 B]: 020, 120, 220, 001, 101, 201, 011, 111, 211 Level 4 [1 DR and 2 B] or [2 DR]: 021, 121, 221, 002, 102, 202, 012, 112, 212, 022, 122, 222 …”