Exposure of viremic donor kidneys to HCV is not associated with opportunistic viral infection

Findings from a recent study provide clinicians with an overview of the relative incidence of opportunistic viral infections after kidney transplantation in patients who received kidneys from donors who tested positive for hepatitis C virus (HCV) (nucleic acid test (NAT) positive) compared with patients who received kidneys from donors who did not test for hepatitis C virus (HCV) (nucleic acid test (NAT) negative).¹

The results of the single-center study conducted at Duke University Hospital suggest that there is no significant difference in viral reactivation of BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) during the first year after kidney transplantation based on the HCV NAT status of the donor kidney.¹

A kidney transplant is generally considered the best treatment for patients with end-stage kidney disease.² However, there are currently more than 100,000 people on national transplant waiting lists and nearly 90,000 are seeking a kidney transplant due to a shortage of available donor kidneys. Many patients are therefore unable to receive a transplant.³ With the development of highly effective, direct-acting antiviral therapies, HCV-NAT-positive kidney transplants are increasingly being used in HCV-NAT-negative recipients. However, concerns about the emergence of opportunistic viral infections remain.1

“There are few reports examining the association between the use of HCV-viremic donor organs and opportunistic viral infections in kidney transplant recipients,” wrote Jennifer Byrns, PharmD, CPP, a clinical pharmacist at Duke Health, and colleagues.¹ “The data are mixed and suggest a potential association with an increased risk of high BKPyV viral loads ≥ 10,000 IU/mL in HCV NAT+ kidney transplant recipients, but overall the incidence of CMV and BKPyV viremia is similar compared to matched cohorts of non-HCV patients. To date, there are no studies that have examined the incidence of EBV viremia in this patient population.”

To determine the frequency of these 3 viral opportunistic infections in HCV-NAT-negative recipients who underwent kidney transplantation using HCV-NAT-positive donor kidneys, researchers conducted a single-center, retrospective case-control study at Duke University Hospital from 2018 to 2021. For inclusion, patients had to be at least 18 years old at the time of transplantation, have received a kidney transplant at Duke University Hospital, and be followed for at least 1 year after transplantation. Patients who were pregnant, had previously undergone transplantation, had undergone multiorgan transplantation, were infected with HIV, or had prior HCV infection that was untreated at the time of transplantation were excluded from the study.¹

HCV-NAT-negative kidney transplant recipients who received kidneys from HCV-NAT-positive donors were matched 1:2 to a matched control group of HCV-NAT-negative kidney recipients transplanted from HCV-NAT-negative donors between July 2013 and August 2021. Nearest neighbor matching was performed using propensity scores derived from logistic regression to adjust for covariates between patients who received organs from HCV-NAT-positive donors and those who did not, adjusting for age, sex, EBV immunoglobulin G serostatus, induction medications used, and pre-transplant panel-reactive class I and II antibodies.¹

The primary outcome was the cumulative incidence of BKPyV, CMV and/or EBV viral infections within 1 year after kidney transplantation. CMV and BKPyV polymerase chain reaction testing on a blood sample was performed per protocol every two weeks for the first 3 months after transplantation and then monthly for the remainder of the first year. Quantitative EBV PCR testing was performed only when clinically indicated.¹

A total of 77 HCV-negative recipients of HCV-NAT-positive kidneys met the inclusion criteria, along with 154 control subjects matched in a 1:2 ratio. In the cohort (n = 231), most organ recipients were black (51.1%) and male (63.6%), and had a mean age of 56 years.¹

The researchers noted that patient profiles were not balanced in terms of CMV serostatus between the two groups, with more patients in the exposed group having received a high-risk CMV donor-positive/recipient-negative organ (33.8% versus 23.4%). Maintenance immunosuppression consisted predominantly of tacrolimus, mycophenolate, and prednisone-based therapy, with no difference in immunosuppression regimens used between groups when analyzed during hospitalization after the index transplant and at 3 months, 6 months, 9 months, and 12 months post-transplant.¹

The overall incidence of opportunistic viral infections after one year was 77% for the exposed group (95% CI, 67%–86%) and 66% for the control group (95% CI, 59%–74%). The cumulative incidence was statistically significant between the two groups (P = .015). After adjusting for confounders such as CMV serostatus, race, and DGF, the hazard ratio was 1.34 (95% CI 0.95–1.89). Among the adjusted covariates, the researchers found that CMV serostatus (D-positive/R-negative) was most strongly associated with viral infection.¹

The 1-year incidence of BKPyV viremia was 41% for the exposed group (95% CI, 30–52%) and 34% for the control group (95% CI, 27–42%; P = .3). The 1-year incidence of EBV viremia was 3% in the exposed group (95% CI, 0%–6%) and 1% in the control group (95% CI, 0%–3%; P = .5). Notably, there were no statistically significant differences between the groups regarding the incidence of BKPyV or EBV viremia.¹

However, the researchers found that the 1-year incidence of CMV viremia was 62% (95% CI, 51%–73%) in the exposed group and 49% (95% CI, 41%–57%) in the control group. They pointed out the statistical significance of the difference in cumulative incidence between the two groups (P = .021), but acknowledged that there were more patients at high risk for CMV viremia in the exposed group due to serostatus (CMV D-positive/R-negative).¹

The researchers pointed out several limitations of these findings, including the single-center, retrospective study design, the reliance on documentation from the electronic medical record and chart review, the potentially limited detection of EBV viremia in both cohorts, the inability to include all confounders as matching variables, and the inability to fully attribute the differences in outcomes between the two groups to exposure to HCV NAT-positive donors.¹

“Our analysis of patients who underwent kidney transplantation between July 2013 and August 2021 and received HCV NAT+ donor kidneys found no difference in viral reactivation of BKPyV, CMV or EBV compared to those who received HCV NAT- donor kidneys,” the researchers concluded.¹ “However, given the significant frequency of viral reactivation in both groups and the associated morbidity, careful monitoring for viral opportunistic infections, particularly during the first year after transplantation, is imperative.”

References

1. ^{Shah K, Katz-Greenberg G, Steinbrink J, et al. Incidence of opportunistic viral infections in recipients of kidneys from positive donors with negative hepatitis C virus nucleic acid testing. Transplant infectious disease. https://doi.org/10.1111/tid.14364}
2. ^{Mayo Clinic. End-stage renal failure. Diagnosis and treatment. October 10, 2023. Accessed September 9, 2024. https://www.mayoclinic.org/diseases-conditions/end-stage-renal-disease/diagnosis-treatment/drc-20354538}
3. ^{HRSA. Organ Donation Statistics. Learn more about organ donation. March 2024. Retrieved September 9, 2024.}