HCV Viremic Donor Kidney Exposure Not Linked to Opportunistic Viral Infection

Jennifer Byrns, PharmD, CPP

Credit: Duke Health

Findings from a recent study are providing clinicians with an overview of the comparative incidence of opportunistic viral infections following kidney transplantation in patients who received kidneys from hepatitis C virus (HCV) nucleic acid test (NAT)-positive donors compared to those who received HCV NAT-negative donor kidneys.¹

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

Kidney transplantation is generally considered to be the best treatment for patients with end-stage kidney disease.² However, with more than 100,000 people currently on the national transplant waitlist and nearly 90,000 seeking a kidney transplant amid a shortage of available donor kidneys, many patients are not able to receive a transplant.³ With the development of highly effective direct-acting antiviral therapy, HCV NAT-positive kidney allografts are more frequently being utilized in HCV NAT-negative recipients, but concerns about the occurrence of opportunistic viral infections remain.1

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

To determine the incidence of these 3 viral opportunistic infections in HCV NAT-negative recipients who have undergone kidney transplantation with HCV NAT-positive donor kidneys, investigators conducted a single-center, retrospective case-control study at Duke University Hospital from 2018 to 2021. For inclusion, patients were required to be ≥ 18 years of age at the time of transplant; have received a kidney transplant at Duke University Hospital; and be followed for ≥ 1 year post-transplant. Patients who were pregnant, previously transplanted, underwent multi-organ transplants, infected with HIV, or previously had HCV that was untreated at the time of transplant were excluded from the study.¹

HCV NAT-negative kidney transplant recipients who received kidneys from HCV NAT-positive donors were compared in a 1:2 ratio to a matched control group of HCV NAT-negative kidney recipients with HCV NAT-negative donors transplanted between July 2013 and August 2021. Nearest-neighbor matching was performed using propensity scores derived from logistic regression to balance covariates between patients receiving organs from HCV NAT-positive donors versus those who did not, including age, gender, EBV immunoglobulin G serostatus, induction medications used, and pre-transplant panel-reactive antibody classes I and II.¹

The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation. CMV and BKPyV polymerase chain reaction testing by blood sample was conducted per protocol every 2 weeks for the first 3 months post-transplant then monthly for the remainder of the first year. Quantitative EBV PCR testing was only completed if clinically indicated.¹

A total of 77 HCV-negative recipients of HCV NAT-positive kidneys met inclusion criteria, along with 154 controls who were matched in a 1:2 ratio. Among the cohort (n = 231), the majority of organ recipients were Black (51.1%) and male (63.6%) with a median age of 56 years.¹

Investigators pointed out patient profiles on CMV serostatus were not well balanced between the 2 groups, with more patients in the exposed group having received a high-risk CMV donor-positive/recipient-negative organ (33.8% vs 23.4%). Maintenance immunosuppression consisted predominantly of a tacrolimus, mycophenolate, and prednisone-based regimen, with no difference in immunosuppression regimens used between groups when analyzed during the index transplant hospitalization, 3 months, 6 months, 9 months, and 12 months post-transplant.¹

The overall incidence of opportunistic viral infections at 1 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 2 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, investigators noted CMV serostatus (D-positive/R-negative) was most 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). Of note, there were no statistically significant differences between the groups for incidence of BKPyV or EBV viremia.¹

However, investigators noted the 1-year incidence of CMV viremia was 62% for the exposed group (95% CI, 51%−73%) and 49% for the control group (95% CI, 41%−57%). They pointed out the statistical significance of the difference in cumulative incidence between the 2 groups (P = .021) but acknowledged there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV D-positive/R-negative).¹

Investigators pointed out multiple limitations to 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 entirely attribute the difference in outcomes between the 2 groups to the exposure to HCV NAT-positive donors.¹

“Our analysis of patients who underwent a kidney transplant between July 2013 and August 2021 and received HCV NAT+ donor kidneys revealed no difference in viral reactivation of BKPyV, CMV, or EBV versus those who received HCV NAT- donor kidneys,” investigators concluded.¹ “However, considering the substantial incidence of viral reactivation in both groups and its associated morbidity, vigilant surveillance for viral opportunistic infections especially during the initial year following transplantation is imperative.”

References

1. ^{Shah K, Katz-Greenberg G, Steinbrink J, et al. Incidence of opportunistic viral infections in hepatitis C virus nucleic acid test negative recipients of kidneys from hepatitis C virus nucleic acid test positive donors. Transplant Infectious Disease. https://doi.org/10.1111/tid.14364}
2. ^{Mayo Clinic. End-stage renal disease. 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 About Donation. March 2024. Accessed September 9, 2024. https://www.organdonor.gov/learn/organ-donation-statistics}