Abstract: TH-PO137

HLA-DR3 Impact on Graft Survival in Membranous Nephropathy: A Tricontinental Registry Study

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Hamilton, Patrick, NHS , Manchester, United Kingdom
  • Poulton, Kay V., Manchester Royal Infirmary, Manchester, United Kingdom
  • Mumford, Lisa L, NHS Blood and Transplant, Bristol, United Kingdom
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
  • Goodrich, Nathan Paul, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Merion, Robert, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • McDonald, Stephen P., ANZDATA Registry, Adelaide, South Australia, Australia
  • Brenchley, Paul E., Manchester Royal Infirmary, Manchester, United Kingdom
Background

Membranous nephropathy (MN) is a rare disease in which a third of patients will need a kidney transplant. The strong genetic predisposition to MN was initially associated with HLA-DR3, and more recently HLA-DQA. It is unknown whether a relation to graft survival is based on presence in the recipient, donor or both.

Methods

We investigated HLA-DR3 mismatching effects on graft survival using data on adult renal transplant recipients with MN from US, UK and Australasian renal transplant registries.
Univariate and multivariable Cox proportional hazard regression (donor age, donor type, registry, recipient ethnicity and transplant year) analyses were fitted to compare overall and death-censored graft survival (GS & DCGS respectively) in the 9 combinations of HLA-DR3 mismatch. Analysis was repeated by grouping HLA-DR3 with other HLA-DR antigens to examine any combined effect that may implicate antigen presentation by HLA-DQ.

Results

There were 6660 MN patients. Using HLA-DR3 homozygous recipient/donor pairs as the reference group, multivariate analysis showed two combinations associated with significantly lower overall and death-censored graft survival: HLA-DR3 homozygous recipients with an HLA-DR3 negative donor (GS - HR 1.92, 95%CI 1.04-3.56, p=0.037 & DCGS - HR 2.18, 95%CI 1.13-4.21, p=0.020), and HLA-DR3 negative recipients with a donor homozygous for HLA-DR3 (GS - HR 2.83, 95%CI 1.01-7.95, p=0.049 & DCGS - HR 3.36, 95%CI 1.16-9.7, p=0.025). In combination with HLA-DR1, HLA-DR6, or HLA-DR7, the same two groups became more significant, with HLA-DR1 appearing to provide the greatest impact. HLA-DR3 +/- DR1 homozygous recipients with an HLA-DR3 +/- DR1 negative donor – HR 1.55, 95%CI 1.05-2.29, p=0.027 and for HLA-DR3 +/- DR1 negative recipients with an HLA-DR3 +/- DR1 homozygous donor – HR 2.36, 95%CI 1.4-3.98, p=0.001

Conclusion

HLA matching at HLA-DR3 does not appear to be associated with graft survival. However graft survival is reduced in HLA-DR3 negative recipients if the donor is HLA-DR3 homozygous, and in HLA-DR3 homozygous recipients receiving an HLA-DR3 negative donor kidney. These results become more significant if HLA-DR1, HLA-DR6 or HLA-DR7 is combined with HLA-DR3, suggesting an association with HLA-DQB polymorphisms