None listed
Conditions
Brief summary
Kidney transplantation is the treatment of choice for patients with end-stage kidney disease (ESKD) because if confers a significant survival benefit compared to dialysis treatment. For the large majority of paediatric and adolescent patients with ESKD, parents are the preferred source of donor kidneys for transplantation. Recent study has suggested that kidneys from mothers are more likely to reject compared to kidneys from fathers, but the reasons for this observation is unknown. This study aims to examine in-depth the potential difference in genetic (i.e. immunological) compatibility between donors and patients) using novel molecular techniques, which may help to better stratify the risk of adverse allograft outcomes after kidney transplantation from mothers and fathers. With these findings, this will enable clinicians and patients/families to make a better-informed decision regarding the selection of the most appropriate parental donor kidneys for transplantation.
Interventions
1) In Australia and New Zealand, each donor-recipient pair will be consented for a single blood sample with DNA isolated for high-resolution molecular human leukocyte antigen (HLA)-typing across HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DPA1, -DPB1, -DQA1, and -DQB1 (if required). In other countries, the sera/DNA are already stored for all donor-recipient pairs that fulfil the inclusion criteria (will need updated waiver of consent) and testing for high-resolution molecular HLA typing will be undertaken
1) In Australia and New Zealand, each donor-recipient pair will be consented for a single blood sample with DNA isolated for high-resolution molecular human leukocyte antigen (HLA)-typing across HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DPA1, -DPB1, -DQA1, and -DQB1 (if required). In other countries, the sera/DNA are already stored for all donor-recipient pairs that fulfil the inclusion criteria (will need updated waiver of consent) and testing for high-resolution molecular HLA typing will be undertaken if required. The high resolution HLA typing will be used to identify and calculate the number of eplet mismatches (using HLAMatchmaker and other computational algorithm), immunogenic/non-immunogenic eplet mismatches, PIRCHE score, amino acid and electrostatic mismatches. Broad antigen low- to intermediate resolution HLA typing would have already been undertaken at time of transplant as part of standard kidney allocation/ transplantation. 2) Participants (recipients and corresponding donors transplanted between January 1990 and December 2020) will be identified from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and country-specific registries/health care records. 3) Patient and donor characteristics of donor and recipient age, donor and recipient sex, time on dialysis prior to transplant, comorbidities (diabetes, coronary artery disease, peripheral vascular disease, cerebrovascular disease), smoking history and types/level of immunosuppressive medications. Outcome measures include rejection, allograft loss, pre-transplant and de novo donor-specific anti-HLA-antibody, kidney allograft biopsy data, hospitalisations and death. These data will be extracted from registry and local healthcare records.
Sponsors
University of Western Australia
Eligibility
Sex/Gender
All
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Paediatric and adolescent patients with ESKD who have received a parental donor kidney transplant aged less than or equal to 18 years between January 1990 and December 2020 will be recruited. Corresponding parental donors will also be recruited.
Exclusion criteria
1) Kidney transplant recipients aged over 18 years of age at time of transplantation. 2) Kidney transplant recipients of deceased donor kidneys. 3) Recipients (and corresponding donors) who are not contactable or alive (at time of recruitment) in Australia and New Zealand will be excluded. Please note that for other countries of United Kingdom, Belgium and Netherlands where a waiver of consent to extract data/utilise stored sera and DNA are permissible, the inclusion of recipient/donor pairs whom are not contactable or are deceased may be included.
Outcome results
None listed