THE ASSOCIATION BETWEEN THE KIDNEY TRANSPLANT RECIPIENT AND DONOR HUMAN LEUCOCYTE ANTIGEN PHENOTYPES AND POST -TRANSPLANT CYTOMEGALOVIRUS DISEASE: A NIGERIAN RESTROPECTIVE REVIEW

Cytomegalovirus (CMV) remains a major cause of morbidity following kidney transplantation. Although human leucocyte antigen (HLA) polymorphisms have been implicated in CMV infection susceptibility, data from sub-Saharan Africa are limited. A possible clustering of HLA-DR13 and HLA-DR15 was noticed amongst kidney transplant recipients (KTR) who developed CMV disease and their donors at Zenith Medical and Kidney Centre, Abuja, Nigeria. We embarked on this study to determine whether this association exists. We investigated the association between recipient and donor HLA phenotypes and post-transplant CMV disease in a Nigerian cohort.

Methods: This was a retrospective cohort study of 256 KTR under active follow-up over an 18-month period (1st March 2024-30th September 2025). Relevant data were extracted from electronic medical records. Time at risk was defined from the later of transplant date or 1st March 2024 until date of CMV diagnosis. Statistical analysis was performed using IBM SPSS software, version 31. Logistic regression analysis was used to adjust for possible confounders.

Incidence of CMV disease in the study period was 16.4%. The mean age of the cases

(48.14±10.88 years) was similar to that of the controls (47.33±13.11 years). The study

participants consisted of 179 males (69.9%) and 77 females (30.1%); male:female ratio

(M:F)=2.3:1. Cases consisted of 23 males (54.8%) and 19 females (45.2%) compared with the

controls which consisted of 156 males (72.9%) and 58 females (27.1%); M:F=1.2:1 vs. 2.7:1,

p=0.02. Majority (98.4%) had non-preemptive kidney transplantation (cases vs. controls: 97.6%

vs. 98.6%; p=0.64). The predominant donor type (95.7%) was living-unrelated (cases vs.

controls: 95.2% vs. 95.8%; p=0.87). There were no deceased donors. Maintenance

immunosuppression consisted of a combination of any three of calcineurin inhibitors, anti-

metabolites, steroids or mammalian target of rapamycin inhibitors. The cases (31%) were more

likely to be on a Sirolimus-based therapy than the controls (7.5%); p<0.001. More cases (16.7%)

had discordant donor-recipient CMV serostatus than the controls (6.5%); p=0.08.

Cytomegalovirus disease was significantly associated with the presence of HLA-DR13 in

recipients (OR 2.33, 95%CI 1.18-4.58, p=0.01) and in donors (OR 2.0, 95%CI 1.02–3.90,

p=0.04) using Chi-square test. However, no significant association was found between the

presence of HLA-DR15 in either the recipients (OR 0.60, 95%CI 0.27-1.32, p=0.20) or donors

(OR 0.77, 95%CI 0.37–1.60, p=0.49). Logistic regression analysis confirmed the association

between CMV disease and HLA-DR13 in recipients (OR 3.25, 95%CI 1.18-8.94, p=0.02), but

not in donors (OR 0.89, 95%CI 0.3-2.48, p=0.83). The mean time from transplant to onset of

CMV disease was 430.9±398.4 days while the mean duration of treatment was 10.83±9.17

weeks. About three-quarters (73.8%) of patients with CMV disease presented with CMV

syndrome and 59.5% required hospitalization. About a quarter (26.2%) had early onset CMV

(within 90 days of transplantation) and more than half (54.8%) had associated neutropenia

(absolute neutrophil count<1500cells/µl). Among the cases, there was acute rejection in 32

(76.2%), graft loss in 14 (33.3%) and death in 12 (28.6%).

 The presence of HLA-DR13 in KTR carries a greater than 3-fold increased risk of post-transplant CMV disease in Nigerian patients. These insights could inform individualized CMV risk stratification and prophylaxis strategies in similar settings.