ABSTRACT
BACKGROUND: Uncontrolled cytomegalovirus (CMV) replication in immunocompromised solid-organ transplant recipients is a clinically relevant issue and an indication of impaired CMV-specific cell-mediated immunity (CMI). Primary aim of this study was to assess the suitability of the immune monitoring tool T-Track® CMV to determine CMV-reactive CMI in a cohort of hemodialysis patients representative of patients eligible for renal transplantation. Positive and negative agreement of T-Track® CMV with CMV serology was examined in 124 hemodialysis patients, of whom 67 (54%) revealed a positive CMV serostatus. Secondary aim of the study was to evaluate T-Track® CMV performance against two unrelated CMV-specific CMI monitoring assays, QuantiFERON®-CMV and a cocktail of six class I iTAg™ MHC Tetramers. RESULTS: Positive T-Track® CMV results were obtained in 90% (60/67) of CMV-seropositive hemodialysis patients. In comparison, 73% (45/62) and 77% (40/52) positive agreement with CMV serology was achieved using QuantiFERON®-CMV and iTAg™ MHC Tetramer. Positive T-Track® CMV responses in CMV-seropositive patients were dominated by pp65-reactive cells (58/67 [87%]), while IE-1-responsive cells contributed to an improved (87% to 90%) positive agreement of T-Track® CMV with CMV serology. Interestingly, T-Track® CMV, QuantiFERON®-CMV and iTAg™ MHC Tetramers showed 79% (45/57), 87% (48/55) and 93% (42/45) negative agreement with serology, respectively, and a strong inter-assay variability. Notably, T-Track® CMV was able to detect IE-1-reactive cells in blood samples of patients with a negative CMV serology, suggesting either a previous exposure to CMV that yielded a cellular but no humoral immune response, or TCR cross-reactivity with foreign antigens, both suggesting a possible protective immunity against CMV in these patients. CONCLUSION: T-Track® CMV is a highly sensitive assay, enabling the functional assessment of CMV-responsive cells in hemodialysis patients prior to renal transplantation. T-Track® CMV thus represents a valuable immune monitoring tool to identify candidate transplant recipients potentially at increased risk for CMV-related clinical complications.
Subject(s)
Cytomegalovirus Infections/diagnosis , Cytomegalovirus/immunology , Immunocompromised Host , Kidney Failure, Chronic/diagnosis , Renal Dialysis , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Cells, Cultured , Cohort Studies , Cytomegalovirus Infections/immunology , Female , Humans , Immediate-Early Proteins/immunology , Immunity, Cellular , Immunoassay , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/therapy , Kidney Transplantation , Male , Middle Aged , Monitoring, Immunologic/methods , Observer Variation , Phosphoproteins/immunology , Sensitivity and Specificity , Viral Matrix Proteins/immunology , Waiting ListsABSTRACT
BACKGROUND: Dry weight assessment (DWA) is essential to efficient therapy of haemodialysis (HD) patients. However, so far objective methods for DWA have not been applicable to daily routine. Thus, exact fluid management in HD remains difficult and is often based on clinical criteria. The aims of this study were (1) to objectively define pre- and post-dialytic ranges of extracellular volume in a large cohort of HD patients (in whom DWA had been defined according to clinical criteria), (2) to compare the hydration status between diabetic and non-diabetic patients, and (3) to assess a patient subgroup that might benefit from correction of target weight. METHODS: We measured fluid overload (FO) prior to a mid-week HD session in 370 randomly selected HD patients (50% with diabetes) from five dialysis centres. A new bioimpedance spectroscopy (BIS) device that implies a validated body composition model was applied. This tool allows correct quantification of extracellular FO or - deficiency in comparison to a healthy reference population (normal range -1.1 to 1.1 L according to the 10th and 90th percentile of measurements). In addition, weight and blood pressure were recorded before and after treatment. RESULTS: Pre-dialytic FO ranged from -0.5 to 4 L and post-dialytic FO from -2.5 to 2 L (10th and 90th percentile of measurements), indicating that on average the hydration status of healthy subjects is considered as the optimal target weight in HD patients. Comparison of FO between diabetic and non-diabetic patients revealed no difference. Based on the consideration that an FO < -1.1 L before and >1.1 L after HD indicates inadequate DWA, we identified 98 (26%) patients who might benefit from correction of target body weight. CONCLUSION: BIS is an interesting, objective method to support clinical DWA. Further studies should be performed to investigate beneficial clinical effects of this approach.
