Cytomegalovirus Infection in a Seroendemic Renal Transplant Population: A Longitudinal Study of Virological Markers

Abstract

Background/Aims: The detection of viremia by polymerase chain reaction (PCR) in cytomegalovirus (CMV) infection in renal allograft recipients has been shown to have a predictive value for disease. However, its diagnostic utility in a population with high background seropositivity has not been defined. This prospective study was undertaken to assess the relationship of CMV DNAemia, and/or IgM seropositivity to CMV disease in a seroendemic transplant population. Methods: Consecutive patients undergoing renal transplantation between August 1997 and February 1998 were enrolled. Blood was sampled before transplantation from the donors and recipients for CMV serology and nested PCR for CMV DNA, and after transplantation from the recipients only at monthly intervals until 6 months. Patients were observed for the development of any CMV-like illness during follow-up. CMV DNA was quantitated using limiting dilution PCR on samples obtained from symptomatic patients at the time of illness and from asymptomatic patients at the end of their 6-month follow-up. Results: A total of 57 recipient-donor pairs were recruited. Immunosuppression was cyclosporine-based in 55 of 57 (95.6%). The CMV serologic status was D+R+ in 55 of 57 and D+R– in 2 of 57 pairs. PCR positivity indicating viremia increased from 5% before transplantation to 95% at 6 months after transplantation. Similarly IgM positivity reached 80% at 3 months and thereafter; positivity for any marker was 100% by 6 months. Viremia was sustained in over half the patients. The incidence of CMV-attributable disease peaked at 3 months, and was predominantly mild and self-limiting. Tissue-invasive disease appeared later in 4 patients (7%). Asymptomatic viremia was seen in 60–70% of patients at each sampling point. The positive predictive value (PPV) of PCR positivity for disease was 35–40%, and the negative predictive value (NPV), 90–100%. However, the high NPV was of use only in the early post-transplant period, negativity for markers declining rapidly with time. Quantitative assay showed significantly higher levels of CMV DNA in symptomatic patients (p = 0.01). A cutoff of 0.001 µg had a specificity of 95% and a PPV of 92.3% for symptomatic CMV disease. Conclusion: Qualitative tests to detect CMV DNAemia and IgM, although useful markers of viremia and active infection, have limited utility for the diagnosis of disease in a seroendemic transplant population. Quantitation of CMV DNAemia may play an important role in diagnosis in such a setting.