Heparin-binding haemagglutinin, a new tool for the detection of latent Mycobacterium tuberculosis infection in hemodialysis patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients. METHODS: On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA). RESULTS: Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT. CONCLUSIONS: The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT.

Prevention of tunneled cuffed hemodialysis catheter-related dysfunction and bacteremia by a neutral-valve closed-system connector: a single-center randomized controlled trial.

BACKGROUND: Hemodialysis (HD) tunneled cuffed catheters may be fitted with neutral-valve closed-system connectors. Such connectors, which are flushed with saline solution and used for 3 consecutive HD sessions, provide a mechanically closed positive-pressure barrier and potentially may be useful to prevent catheter-related bacteremia and dysfunction. STUDY DESIGN: Single-center randomized controlled trial. SETTING & PARTICIPANTS: 66 adult HD patients with a tunneled cuffed catheter. INTERVENTION: Neutral-valve closed-system connector (Tego Needlefree Hemodialysis Connector) versus trisodium citrate, 46.7%, locking solution (Citra-Lock; control group). OUTCOMES: Primary composite outcome was the incidence rate of catheter-related dysfunction or bacteremia. Secondary outcomes were the separate incidence rates of catheter-related dysfunction and bacteremia and the cost of both procedures. MEASUREMENTS: Catheter dysfunction was defined as the requirement of urokinase and/or a mean blood flow ≤250 mL/min during 2 consecutive HD sessions. Catheter-related bacteremia was defined as ≥2 positive blood cultures. Time of catheter use was calculated and the incidence rate of complications was expressed per 100 person-years. RESULTS: 66 patients were followed up for a median of 86 (IQR, 29-200) days. The composite primary outcome was not significantly reduced in the closed-system-connector intervention group versus the citrate-locking-solution control group (63.56 vs 71.51 per 100 person-years; P = 0.3). Catheter dysfunction in the intervention group was not decreased versus controls (59.59 vs 51.64 per 100-person-years; P = 0.9). Only 6 catheter-related bacteremia events were identified, one in the intervention group (3.97 vs 19.86 per 100 person-years; P = 0.06). LIMITATIONS: Small size of the patient population and single-center study. CONCLUSIONS: Superiority of the closed-system connector in terms of prevention of the primary efficacy end point compared to the standard locking solution was not observed. Further evaluation in a larger study is suggested.

Sarcoma-like pyogenic granuloma of the thumb and respiratory restrictive syndrome in a non-compliant hemodialysis patient.

Pyogenic granuloma is a benign vascular tumor of the skin or mucosae usually observed after irritative processes. We report the case of a non-compliant hemodialysis patient with severe hyperparathyroidism who rapidly developed growing pyogenic granuloma of the distal part of the left thumb. This tumor mimicked sarcoma and caused recurrent bleeding during hemodialysis sessions. Hand radiograph revealed an osteolytic lesion compatible with a brown tumor. Among other brown tumors, several of those found in the ribs were responsible of a severe respiratory restrictive deficit. This report highlights the difficulty to choose the adequate treatment of severe hyperparathyroidism, and discusses the benefit/risk balance of performing parathyroidectomy.

Influenza A/H1N1 vaccine in patients treated by kidney transplant or dialysis: a cohort study.

BACKGROUND AND OBJECTIVES: In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: ≥4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. RESULTS: The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39). CONCLUSIONS: The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

Cytotoxicity of mononuclear cells as induced by peritoneal dialysis fluids: insight into mechanisms that regulate osmotic stress-related apoptosis.

OBJECTIVE: High glucose content of peritoneal dialysis fluids (PDFs) has been shown to contribute to loss of peritoneal function during long-term peritoneal dialysis. However, hyperosmolality and hypertonicity of PDF are usually seen as similar stress events inducing osmotic stress-induced programmed cell death. In this study, we examined the impact of various osmotic agents on apoptosis induced by hyperosmolar PDFs, focusing on the mechanisms underlying the lethal effects of PDFs on peripheral blood mononuclear cells (PBMCs). METHODS: We assessed apoptosis and necrosis by annexin V-propidium iodide (PI) labeling, and caspase-3 activity by fluorescence assay. F-actin remodeling was measured using fluorescent phalloidin labeling. RESULTS: Hyperosmolality does not cause the cytotoxicity observed with PDF, but exposure to agents incapable of permeating cell membranes results in a significant increase in the percentage of apoptotic PBMCs by annexin V-PI labeling, which is confirmed by the increase in caspase-3 activity. Interestingly, inhibition of caspase-3 by Z-VAD-FMK did not suppress apoptosis. Extracellular hypertonicity produced polymerization of filamentous actin and cell shrinkage, which displayed similar time courses. Cell shrinkage was blocked by cytochalasin D, indicating an active role for actin cytoskeleton in hypertonicity-induced cell shrinkage. F-actin polymerization was related to an increase in intracellular ionic strength. Finally, we excluded a direct role for actin remodeling in osmotic stress-induced programmed cell death. CONCLUSIONS: Exposure to osmolytes that cannot penetrate cell membranes results in a hypertonicity-induced apoptosis that cannot be blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK. In addition, extracellular hypertonicity induced by impermeant solutes produces F-actin polymerization through an increase in intracellular ionic strength. The remodeling of the cytoskeleton does not modulate apoptosis but participates in cell shrinkage.