Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation

Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation. OBJECTIVE: The aim of this study was to determine the HHV-6 seroprevalence among donor-recipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation. METHODS: 46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6(Pambio - USA) and CMV-(Roche - USA). A frozen whole blood sample collected weekly (from the 1st to the 6th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen - Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest - Germany) from the 4th to the 12th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched. RESULTS: Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6x54.8%; p = 0.005 [3.9 (1.4-10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p = 0.412). Median VL was 125 copies/mL (53-11.264), and the median Ag was 21 +cells (2-740). There was no association between HHV-6 and CMV activation after transplantation (p = 0.441), neither concerning DCMV (p = 0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or - (p = 0.206 and p = 0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p = 0.009) and fungal (p = 0.001) infections, and higher number (p = 0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p = 0.033 and p = 0.001). CONCLUSION: Latent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.

BKV-infection in kidney graft dysfunction

INTRODUCTION: BKV nephropathy (BKN) causes kidney graft loss, whose specific diagnosis is invasive and might be predicted by the early detection of active viral infection. OBJECTIVE: Determine the BKV-infection prevalence in late kidney graft dysfunction by urinary decoy cell (DC) and viral DNA detection in urine (viruria) and blood (viremia; active infection). METHODS: Kidney recipients with >1 month follow-up and creatinine >1.5 mg/dL and/or recent increasing >20 percent (n = 120) had their urine and blood tested for BKV by semi-nested PCR, DC searching, and graft biopsy. PCR-positive patients were classified as 1+, 2+, 3+. DC, viruria and viremia prevalence, sensitivity, specificity, and likelihood ratio (LR) were determined (Table 2x2). Diagnosis efficacy of DC and viruria were compared to viremia. RESULTS: DC prevalence was 25 percent, viruria 61.7 percent, and viremia 42.5 percent. Positive and negative patients in each test had similar clinical, immunossupressive, and histopathological characteristics. There was no case of viremia with chronic allograft nephropathy and, under treatment with sirolimus, patients had a lower viruria prevalence (p = 0.043). Intense viruria was the single predictive test for active infection (3+; LR = 2.8).1,6-4,9 CONCLUSION: DC, BKV-viruria and -viremia are commun findings under late kidney graft dysfunction. Viremia could only be predicted by intense viruria. These results should be considered under the context of BKN confirmation.

The incidence of cytomegalovirus infection in lung transplant recipients under universal prophylaxis with intravenous ganciclovir

The best strategy for control of cytomegalovirus (CMV) infection in lung transplant patients is still not determined. The aim of this study was to document the incidence of CMV infection in a cohort of lung transplant recipients under universal prophylaxis with intravenous ganciclovir. All patients received immunosuppressive regimens consisting of cyclosporine, azathioprine, and prednisone. Regardless of CMV serostatus, intravenous ganciclovir was prescribed for every patient in the first 3 months post-transplantation. CMV infection was defined as the detection of CMV pp65 in leukocytes. Eighty-two lung transplant patients were included over a 5-year period. The incidence of CMV infection in the first year post-transplantation was 68.3 percent, occurring after a median length of 114 days (range, 26-343 days). This study revealed a high incidence of CMV infection in the first year following lung transplantation despite prolonged universal ganciclovir prophylaxis.