*Purpose: Cytomegalovirus (CMV) is the most common viral infection that occurs after solid organ transplantation. The incidence of CMV infection or disease (I/d) varies based on the type of transplant, the serological match (CMV IgG +/-) between donor (D+/D-) and recipient (R+/R-), and post-transplant immunosuppression used. Prior literature suggests that certain HLA alleles are associated with an increased risk of CMV infection in renal transplant recipients (RTRs), while other alleles have shown a protective effect. Our study aimed to further investigate the relationship between CMV I/d development risk and HLA alleles in RTRs.

*Methods: We analyzed 379 RTRs who received a transplant between January 2016 – December 2019 at Henry Ford Transplant Institute through a retrospective case control methodology. We collected data on RTRs demographics (age, gender, ethnicity), comorbidities, induction immunosuppression, type of kidney transplant, CMV risk status (high risk – D+/R-; intermediate risk – R+; low risk – D-/R-), and CMV prophylaxis given. The HLA-A, -B, and -DR allele types were compared between RTRs with and without CMV infection through a univariate and multivariate analysis.

*Results: Of the 379 RTRs, 57.5% were male and average RTR age was 52 years. 53.5% were Caucasian and 38.4% African American. 24.2% of RTRs were low risk, 57.4% were intermediate risk, and 18.4% were high risk. A total of 15% of RTRs (n = 57) developed CMV I/d, of which 44% had tissue-invasive disease and 56% had viremia. 37.7% of the high-risk RTRs developed CMV I/d. On regression analysis, there appeared to be a significant association between CMV I/d and CMV risk status when examined as a continuous variable (Odds Ratio (OR) 6.032; p<0.001). There was also an association between CMV I/d and African American ethnicity (OR 3.736; p<0.001). We found that recipient HLA-DR9 allele (OR 5.233; p<0.011) appeared to be a significant independent predictor of CMV I/d. There also seemed to be a significant association between donor HLA-A3 allele (OR 4.572; p<0.001) and CMV I/d. 16.1% of RTRs experienced acute or chronic allograft rejection with graft failure in 12.7%. Overall patient mortality was 8.2%, independent of HLA allele association.

*Conclusions: Certain recipient HLA alleles (HLA-DR9) may be associated with an increased risk of developing CMV I/d in RTRs. The reason for the significance between donor HLA-A3 allele and CMV risk is unclear. In addition to traditional risks for CMV, the HLA phenotype may supplement risk stratification for development of CMV I/d in RTRs and guide post-transplant management. Further studies using a multi-center approach to examine the correlation between post-transplant CMV risk with HLA alleles in various populations would be valuable.

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