Role of highly sensitive nucleic acid amplification testing for plasma cytomegalovirus DNA load in diagnosis of cytomegalovirus gastrointestinal disease among kidney transplant recipients
AbstractBackgroundHigh plasma cytomegalovirus (CMV) DNA load is generally associated with CMV tissue‐invasive disease in solid organ transplant recipients. However, some tissue‐invasive diseases, especially CMV gastrointestinal (GI) disease, have undetectable to very low plasma CMV DNA loads. Highly sensitive nucleic acid amplification testing (NAAT) has been increasingly used to quantify low‐level CMV DNA loads. Our primary objective was to investigate the epidemiology of CMV GI disease and evaluate the validity of plasma CMV NAAT for the diagnosis of CMV GI disease in kidney transplant (KT) recipients.MethodsWe conducted a retrospective study of all KT recipients who developed CMV GI disease from January 2016 to December 2018. Plasma CMV DNA load was measured using real‐time PCR. The cut‐off value of plasma CMV DNA load for diagnosing and risk factors of CMV GI disease were analyzed.ResultsA total 17 (3.4%) cases of CMV GI disease occurred in 494 KT recipients. Fifteen (88%) patients had CMV D + /R + serostatus. Fourteen (82%) patients developed CMV GI disease within 6 months after KT. Plasma CMV DNA loads were detectable in all (100%) patients with a median load 11,102 (IQR 2,935‐107,160) IU/ml. A plasma CMV DNA load of 4,063 IU/ml was established as al cut‐off for diagnosing CMV GI disease (AUC 0.74, sensitivity 76.5%, specificity 70%, PPV 68, NPV 78). In multivariate analysis, prolonged cold ischemic time (HR 1.14, 95% CI 1.05‐1.23, P = .002) and CMV D + /R ‐ serostatus (HR 9.31, 95% CI 2.12‐40.74, P = .003) were associated with CMV GI disease.ConclusionsUsing highly sensitive NAAT could potentially assist in the diagnosis of CMV GI disease in a CMV D + /R + serostatus setting. KT recipients with CMV seromismatch and prolonged cold ischemic time are at higher risk of CMV GI disease.
Predictors of CMV Infection in CMV-Seropositive Kidney Transplant Recipients: Impact of Pretransplant CMV-Specific Humoral Immunity
Abstract Background Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a relatively lower risk of CMV infection than CMV-seronegative recipients who receive allograft from CMV-seropositive donors, some patients remain at risk of CMV infection after transplant. We investigated the pretransplant CMV-specific humoral immunity (CHI) and other CMV infection predictors in CMV-seropositive kidney transplant (KT) recipients. Methods This retrospective study was conducted on adult CMV-seropositive KT recipients during 2017 and 2018. The cumulative incidence of CMV infection was estimated using the Kaplan-Meier method. CHI, measured with an enzyme-linked fluorescent immunoassay and other predictors for CMV infection, was analyzed using Cox proportional hazards models. Results Of the 340 CMV-seropositive KT recipients (37% female; mean ± SD age, 43 ± 11 years), 69% received deceased-donor allograft and 64% received induction therapy. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%. In multivariate analysis, low pretransplant CHI (defined as anti-CMV immunoglobulin [IgG] titer <20 AU/mL) was significantly associated with CMV infection (hazard ratio [HR], 2.98; 95% CI, 1.31–6.77; P = .009). Other significant predictors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06; P = .005), antithymocyte induction therapy (HR, 2.90; 95% CI, 1.09–7.74; P = .033), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10; P = .002). Conclusions A low pretransplant CHI is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. A quantitative anti-CMV IgG assay could potentially stratify CMV-seropositive patients at risk of CMV infection after KT.