Abstract
Background and Aims
Counselling kidney transplant candidates for their personalised risk of developing post-transplantation diabetes mellitus (PTDM) requires an understanding of risk factors. While some risk factors are well defined (e.g. age, ethnicity, body mass index), others like HLA typing are heterogeneously reported and lack consistency. The aim of this study was to investigate the association between HLA alleles and PTDM risk.
Method
Data was retrospectively extracted from hospital informatics systems for all kidney transplant recipients at a single-centre between 2007 and 2018, with patients excluded if they had pre-existing diabetes. Electronic patient records were then manually searched and records linked to various sources (e.g. NHS Blood and Transplant tissue typing, Hospital Episode Statistics, national death registry) to create a well-phenotyped cohort. Standard immunosuppression for all kidney transplant recipients during this study period was basiliximab induction with maintenance immunosuppression consisting tacrolimus, mycophenolate mofetil and low-dose corticosteroids. PTDM classification was aligned with International Consensus recommendations.
Results
Data was extracted for 1,560 kidney allograft recipients, with median follow up 5.4 years (IQR 2.7-8.7 years) up to October 2018. PTDM developed in 243 kidney transplant recipients (incidence 15.6%). A range of HLA alleles were examined (e.g. HLA-A, HLA-B, HLA-Cw, HLA-Bw, HLA-DR and HLA-DQ) but only the presence of HLA-Cw12 allele was associated with risk for PTDM (27.4% versus 14.3%, p<0.001) along with a selection of predominately recipient- and transplant related variables. In a logistic regression model, adjusted for all variables with a p-value <0.15 on univariate analysis, recipient HLA-Cw12 was found to be an independent risk factor associated with development of PTDM (Odds Ratio 1.793 [95% confidence interval 1.070-3.002], p=0.027) along with recipient female sex, recipient age, recipient BMI and recipient non-white ethnicity.
Conclusion
HLA-Cw12 allele in the kidney transplant recipient is independently associated with development of PTDM, although it is important to acknowledge association does not imply causality. This association has not been previously reported and requires validation and further investigation to understand any possible underlying biological mechanisms.
High Incidence of Rejection Caused By Donor Specific Anti-HLA-DQ Antibodies in Kidney Transplant Recipients.