Transition from antigenemia to quantitative nucleic acid amplification testing in cytomegalovirus-seropositive kidney transplant recipients receiving preemptive therapy for cytomegalovirus infection

Abstract

Due to the high costs, the strategy to reduce the impact of cytomegalovirus (CMV) after kidney transplant (KT) involves preemptive treatment in low and middle-income countries. Thus, this retrospective cohort study compared the performance of antigenemia transitioned to quantitative nucleic acid amplification testing, RT-PCR, in CMV-seropositive KT recipients receiving preemptive treatment as a strategy to prevent CMV infection. Between 2016 and 2018, 363 patients were enrolled and received preemptive treatment based on antigenemia (n = 177) or RT-PCR (n = 186). The primary outcome was CMV disease. Secondarily, the CMV-related events were composed of CMV-infection and disease, which occurred first. There were no differences in 1-year cumulative incidence of CMV-disease (23.7% vs. 19.1%, p = 0.41), CMV-related events (50.8% vs. 44.1%, p = 0.20), neither in time to diagnosis (47.0 vs. 47.0 days) among patients conducted by antigenemia vs. RT-PCR, respectively. The length of CMV first treatment was longer with RT-PCR (20.0 vs. 27.5 days, p < 0.001), while the rate of retreatment was not different (14.7% vs. 11.8%, p = 0.48). In the Cox regression, acute rejection within 30 days was associated with an increased the risk (HR = 2.34; 95% CI = 1.12-4.89; p = 0.024), while each increase of 1 mL/min/1.73 m² of 30-day eGFR was associated with a 2% reduction risk of CMV-disease (HR = 0.98; 95% CI = 0.97-0.99; p = 0.001). In conclusion, acute rejection and glomerular filtration rate are risk factors for CMV disease, showing comparable performance in the impact of CMV-related events between antigenemia and RT-PCR for preemptive treatment.

Figure 1

Flowchart of the population. The transition period is from March 2017 to February 2018, when the service had adopted both methods for viremia detection. CMV, cytomegalovirus; HLA, human leukocyte antigen; mTOR, mammalian target of rapamycin; RT-PCR, real-time polymerase chain reaction.

Figure 2

Levels of tacrolimus according to groups (eras) in the first year of transplantation. The mean of eGFR between eras (antigenemia and RT-PCR) was compared by generalized estimating equation modeling and adjusted by Bonferroni test. Squares and circles in the plot represent mean and bars the 95% confidence interval. PCR, real-time polymerase chain reaction.

Figure 3

Primary and secondary outcomes: CMV-related events, CMV disease, acute rejection and graft function. (A) cumulative incidence of the first CMV-related event (infection or disease) according to the era. (B) cumulative incidence of CMV disease according to the era. (C) cumulative incidence of acute rejection according to the era. (D) graft function assessed by estimated glomerular filtration rate according to the era. In the figures (A–C), the P-value was calculated by log-rank. The means of graft function over time and according to era were compared by generalized estimating equation modeling and adjusted by Bonferroni test. Squares and circles in the plot represent mean and bars the 95% confidence interval. RT-PCR, real-time polymerase chain reaction].