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Abstract: PO2164

Association Between Recipient-Donor HLA Genotypes and Recurrent Membranous Nephropathy After Kidney Transplantation

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Chung, Edmund YM, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
  • Blazek, Katrina, The University of Sydney, Sydney, New South Wales, Australia
  • Sharma, Ankit, Westmead Hospital, Westmead, New South Wales, Australia
  • Kim, Siah, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
  • Teixeira-Pinto, Armando, The University of Sydney, Sydney, New South Wales, Australia
  • Wong, Germaine, The University of Sydney, Sydney, New South Wales, Australia
  • Alexander, Stephen I., Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
Background

Recurrent membranous nephropathy (MN) occurs in up to 40% of kidney transplant recipients (KTRs) and is a major cause of graft loss. Recipient with alleles at the HLA-D loci were found to have an increased risk of disease recurrence in KTRs with primary MN. However, the association between recipient-donor HLA characteristics and disease recurrence has not been explored.

Methods

We integrated data from two registries: United Network for Organ Sharing, and Australian and New Zealand Dialysis and Transplant registries between 1963 and 2020. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for variable selection. The penalization parameter was chosen by cross-validation and the covariates with non-zero coefficients were included in a logistic regression, together with class, and fitted using maximum likelihood. The model performance was evaluated using C-statistics.

Results

8058 KTRs with primary MN were included and 232 had recurrent MN. Of the 266 variables, group LASSO selected 59 variables considered as variables of importance and were included in the adjusted logistic regression model. Recipient HLA genotype at DR11 (odds ratio, 95% confidence interval) (1.81, 1.30-2.51, p<0.001), B38 (1.93, 1.00-3.43, p=0.04), and B46 (6.75, 1.55-26.30, p=0.007) and donor-recipient HLA-B65 match (3.38, 1.07-8.85, p=0.02) were associated with an increased risk of recurrent MN, adjusted for recipient sex, ethnicity, comorbidities (diabetes, hepatitis C and cancer), immunosuppression regime (T cell depletion induction therapy, B cell depletion induction therapy, tacrolimus, corticosteroid, or other maintenance therapy), donor type, biopsy-proven rejection, and country of origin. The overall performance of the model was good (C-statistic 82%).

Conclusion

Recipient HLA-DR11, B38, B46 and donor-recipient HLA-B65 match were associated with an increased risk of recurrent MN in KTRs.

Figure 1. Recipient-donor HLA characteristics associated with recurrent membranous nephropathy in kidney transplant recipients