This study investigated the link between specific HLA alleles (genes related to immune system function) and the risk of developing post transplantation diabetes (PTDM) in kidney transplant recipients. Researchers analysed data from 1,560 non-diabetic kidney transplant patients over a median of 33 months. They found that certain HLA alleles, such as Cw12 and DQ4, were associated with an increased risk of PTDM. For White recipients, the presence of the B58 allele also increased PTDM risk. These findings suggest that HLA typing could help identify patients at higher risk for PTDM before transplantation. However, further research is needed to understand the underlying biological mechanisms.

Abstract

Background

The association between specific HLA alleles and risk for post transplantation diabetes (PTDM) in a contemporary and multiethnic kidney transplant recipient cohort is not clear.

Methods

In this single-centre analysis, data were retrospectively analysed for 1560 nondiabetic kidney transplant recipients at a single centre between 2007 and 2018, with median follow-up of 33 mo (interquartile range 8–73). HLA typing methodology was by DNA analysis and reported at the resolution required for the national allocation scheme. Diagnosis of PTDM was aligned with International Consensus recommendations.

Results

PTDM developed in 231 kidney transplant recipients. Exploring 99 HLA alleles, the presence of Cw12, B52, B38, B58, DQ4, A80, and DR13 and the absence of DQ3 and DR04 were associated with significant increases in PTDM risk. In a multivariable Cox regression model, adjusting for other clinical risk factors for PTDM, the presence of Cw12 (hazard ratio [HR], 1.57; 95% CI, 1.08-2.27; P = 0.017) and DQ4 (HR, 1.78; 95% CI, 1.07-2.96; P = 0.026) were found to be independent risk factors for PTDM. There was also evidence that the presence of B58 increases PTDM risk within the subgroup of recipients of White ethnicity (HR, 5.01; 95% CI, 2.20-11.42; P < 0.001).

Conclusion

Our data suggest that specific HLA alleles can be associated with PTDM risk, which can be used pretransplantation for PTDM risk stratification. However, association is not causality, and this work requires replication and further investigation to understand underlying biological mechanisms.

Authors: Nuvreen Phagura , Azm Hussain , Alice Culliford , James Hodson , Felicity Evison , Suzy Gallier  Richard Borrows , Hanna A Lane  David Briggs, Adnan Sharif