Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients

Abstract

Background: Cytomegalovirus (CMV) disease is the most common infectious complication after solid organ transplantation, frequently affecting the gastrointestinal (GI) tract. There are limited data on quantitative polymerase chain reaction (qPCR) for plasma CMV DNA as an adjunct diagnostic method for GI tract disease in kidney and liver transplant recipients.

Methods: We reviewed all records of adult kidney and liver transplant recipients with a GI tract biopsy and plasma CMV qPCR result within 15 days of biopsy during a 6.5-year period at our center. CMV GI tract disease was defined as histopathologic evidence of CMV on biopsy by immunohistochemistry or visualization of inclusion bodies.

Results: GI tract biopsy and qPCR results were available for 81 kidney and liver transplant recipients; 20 cases of confirmed CMV GI tract disease were identified. Overall, the sensitivity of qPCR for diagnosing CMV GI tract disease was 85% (95% confidence interval [CI], 61%-96%), and the specificity was 95% (95% CI, 85%-99%). For CMV-seronegative recipients (R(-)) with CMV-seropositive donors (D(+)), the sensitivity of qPCR was 100% (95% CI, 59%-99%), and the specificity was 80% (95% CI, 30%-99%). The lowest sensitivity was observed in CMV D(+)/R(+) cases (72.7%; 95% CI, 39%-93%). The mean plasma CMV copy number in patients with GI tract disease was 3.84 log10 (38 334 copies/mL).

Conclusions: Plasma CMV qPCR had good sensitivity and excellent specificity for CMV GI tract disease in kidney and liver transplant recipients. Its sensitivity was 100% in CMV D(+)/R(-) cases but 72.7% in CMV D(+)/R(+) cases. This variation in assay performance according to host serostatus may reflect differences in disease pathogenesis.

Keywords: CMV; colitis; kidney and liver transplant recipients; viremia.

Figure 1.

Timing of cytomegalovirus (CMV) gastrointestinal (GI) tract disease diagnosis in transplant recipients relative to transplantation. Abbreviations: D⁺, donor CMV seropositive; D⁻, donor seronegative; R⁺, recipient seropositive; R⁻, recipient seronegative.

Figure 2.

Cytomegalovirus (CMV) plasma viral load (DNA) for each patient with suspected CMV gastrointestinal (GI) tract disease, measured within 15 days of GI tract biopsy. Solid circles represent patients with detectable CMV DNA; open circles, patients with undetectable CMV DNA, at the lower limit of detection of the assay in use at the time. Three quantitative polymerase chain reaction assays were used during the study period, with varying lower limits of detection (600, 300, and 50 copies/mL) represented by dotted lines.

Figure 3.

Positive (A) and negative (B) predictive values calculated from the sensitivity and specificity for the detection of plasma cytomegalovirus (CMV) DNA by quantitative polymerase chain reaction over a range of hypothetical prevalence values. Dotted lines represent prevalence of CMV gastrointestinal tract disease among patients in this series in whom biopsy was performed (24.7%), in whom the positive and negative predictive values were 0.85 and 0.94, respectively.