Diagnosing cytomegalovirus disease in CMV seropositive renal allograft recipients: A comparison between the detection of CMV DNAemia by polymerase chain reaction and antigenemia by CMV pp65 assay

Abstract

The optimal diagnostic test for CMV disease in renal allograft recipients in a locality with a high CMV seropositive rate has not been fully determined. We compared the usefulness of the CMV pp65 antigenemia (CMV-Ag) assay with the detection of DNAemia by a nested polymerase chain reaction (PCR) method in diagnosing CMV disease in 56 renal allograft recipients, of whom 50 (89.2%) were CMV seropositive prior to transplant (tx). Positive CMV-Ag assays were found in 126/281 samples (44.8%) of 27 patients (48.2%) of whom five had seven episodes of CMV disease. The remaining 22 patients were asymptomatic. The symptomatic patients had significantly higher median peak CMV-Ag levels than the asymptomatic patients [800 (160-1380) vs. 5 (1-604) per 2 x 10 5 peripheral blood leukocyte (PBL), p < 0.0001]. One hundred and eight samples were tested by both CMV-Ag and PCR methods. Out of the 108 samples, 89 showed concordant results (37 positive and 52 negative for both tests). Seventeen samples of 11 patients were CMV-Ag negative/PCR positive. Out of these 11 patients, two had CMV disease and the discrepancy in the results was due to blood samples taken after the start of ganciclovir therapy. Falsely negative PCR tests were found in two samples of two patients with positive CMV-Ag assays. With a cutoff antigenemia level of 100 per 2 x 10 5 PBL, the sensitivity, specificity, positive and negative predictive values for diagnosing CMV disease were 100, 96, 71.4 and 100%, respectively. On the other hand, CMV DNAemia was detected in many asymptomatic patients, and the PCR test results correlated poorly with the clinical manifestations of the disease. In symptomatic patients undergoing ganciclovir therapy, the quantification of antigenemia level allowed the assessment of treatment efficacy. In addition, positive CMV-Ag assays at the end of therapy were associated with the subsequent relapse of CMV disease in two patients. The high specificity, together with the short processing time of 4 h, make the CMV-Ag assay the test-of-choice for diagnosing, CMV disease in a renal transplant population with a predominance of CMV seropositive patients.