Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

BACKGROUND: The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study. METHODS: Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function. RESULTS: 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis. CONCLUSIONS: Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Early diagnosis of miliary tuberculosis in a hemodialysis patient by combining two interferon-γ-release assays: a case report.

BACKGROUND: Patients with end-stage renal disease undergoing chronic hemodialysis (HD) are at high risk to develop tuberculosis (TB) associated with a high mortality rate. TB diagnosis is often delayed due to non-specific symptoms, frequent extra-pulmonary manifestations, and rare microbiological confirmation. This case report illustrates the clear added value of combined interferon-γ -release assays (IGRA) in response to different mycobacterial antigens for an early diagnosis of TB in HD patients. CASE PRESENTATION: We report the case of an Egyptian patient under chronic HD treatment, who presented with recurrent episodes of fever and myalgia of unknown origin, associated with an important inflammatory syndrome. These episodes resolved partially or completely within less than 1 month without any treatment but recurred 10 times within 3 years. Chest Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18FDG PET-CT) demonstrated several active mediastinal lymphadenopathies. TB was the first suspected diagnosis but cultures and polymerase chain reaction (PCR) remained negative on a mediastinal lymph node aspiration. In contrast, the results from two different IGRA performed on blood were highly suggestive of TB disease. Several granulomas, some of them with central non-caseating necrosis, were demonstrated on a pulmonary nodule obtained by thoracoscopic resection, but PCR and culture remained negative for M. tuberculosis. Three years after the initial symptoms, a new PET-CT revealed a retro-clavicular lymphadenopathy in addition to the mediastinal lymphadenopathies, and the M. tuberculosis culture performed on the resected lymphadenopathy was positive. Antibiotic treatment for TB was started and resulted in a clear improvement of the patient's clinical condition, allowing him to successfully receive a renal graft. CONCLUSIONS: In view of the high frequency of TB in patients undergoing chronic HD and of the limitations of the classical diagnosis procedures, nephrologists have to diagnose TB mostly on clinical suspicion. We demonstrate here that the use of a combined IGRA to two different mycobacterial antigens may significantly raise the index of suspicion and help clinicians to decide starting anti-TB treatment in HD patients.

Vascular access type and mortality in haemodialysis: a retrospective cohort study.

BACKGROUND: Haemodialysis patients have a high mortality rate. Part of this can be attributed to vascular access complications. Large retrospective studies have shown a higher mortality in patients dialysed with a catheter, which is mostly ascribed to infectious complications. Since we observe very little infectious complications in our haemodialysis patients, the aim of our study was to assess if we could still detect a difference in survival according to vascular access type. METHODS: Patients that started chronic haemodialysis treatment between 1/1/2007 and 31/12/2016 at the 'Universitair Ziekenhuis Brussel' were retrospectively studied. The time to death was studied as a function of the two main vascular access types using survival analysis, considering the type of vascular access at the initiation of dialysis or as time varying, and accounting for the available baseline characteristics. RESULTS: Of 374 patients 309 (82.6%) initiated haemodialysis with a catheter, while 65 patients initiated with an arteriovenous access. Vascular access type during follow-up did not change in 74% of all patients. A Kaplan Meier plot did not suggest a survival dependent on the vascular access type at start. An extended cox proportional hazard analysis showed that vascular access type was not independently correlated with mortality. However, age, history of congestive heart failure and active cancer at initiation of dialysis were independently associated with mortality. CONCLUSIONS: In this retrospective cohort study, haemodialysis vascular access type was not independently correlated with patient survival, even after taking into account change of vascular access over time.

Efficacy of urokinase lock to treat thrombotic dysfunction of tunneled hemodialysis catheters: A retrospective cohort study.

BACKGROUND:: There are few data to inform decisions about the optimal management of occluded tunneled cuffed hemodialysis catheters with thrombolytic locking solutions. The effect of dose, dwell-time, and number of administrations remains controversial. METHODS:: In this retrospective single-center review of tunneled cuffed catheters used between 2010 and 2014, restoration of blood flow as well as pre- and post-pump pressures after either short (30 min) or prolonged (48-72 h) administration of 100,000 IU of urokinase locking solution was evaluated in all thrombotic dysfunctions. We also assessed if multiple urokinase locks for the same thrombotic dysfunction event were more efficient to restore catheter performance than single administration. RESULTS:: Data on 773 thrombotic events in 148 patients (236 catheters) were collected during observation period. After urokinase treatment, blood flow and pre-pump pressure improved (median of 50 mL/min and 20 mmHg) whereas post-pump pressure decreased (median of 15 mmHg) (all P < 0.0001). The short thrombolytic procedure, used in more severely dysfunctional catheters, resulted in significantly larger improvements in catheter function than the long procedure. Multiple administrations for the same thrombotic event further improved access function in case of persisting dysfunction after first lock but had no added beneficial effect if blood flow and/or pump pressures were normalized after first urokinase lock. CONCLUSION:: Both short and prolonged administration of urokinase locks were efficient in restoring blood flow and pre- and post-pump pressures in dialysis catheters with thrombotic dysfunction. Multiple urokinase locks provide added benefit on these outcomes only in case of persisting dysfunction after the first lock.

Urokinase-containing locking solution in the prevention of dialysis catheter dysfunction: a double blind randomized controlled trial.

INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction. METHODS: Patients with a history of at least two separate TCC thrombotic dysfunctions treated with urokinase lock during the 6 months preceding inclusion are recruited in eight Belgian dialysis units. Patients are randomized in two groups: the control group receiving Taurolock™-HEP500 (heparin 500 IU/mL, taurolidine, citrate 4%) after each hemodialysis session and the treatment group receiving Taurolock-U 25,000 (urokinase 25,000, taurolidine, citrate 4%) once a week and the standard Taurolock-HEP500 at the end of the two others sessions. The primary outcome is the incidence rate of TCC thrombotic dysfunction defined by the use of urokinase. The secondary outcomes are the incidence rate of TCC removal and systemic thrombolysis. For the study, both patients and healthcare staff are blinded to treatment allocation. CONCLUSIONS: The present trial is the first to investigate the effect of Taurolock-U 25,000 catheter lock once a week as secondary prevention in hemodialysis patients with the highest risk of TCC-related thrombotic dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

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.

Risk stratification of latent tuberculosis defined by combined interferon gamma release assays.

BACKGROUND: Most individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. Here, we provide an approach to stratify LTBI based on IFN-γ responses to two antigens, the recombinant Early-Secreted Antigen Target-6 (rESAT-6) and the latency antigen Heparin-Binding Haemagglutinin (HBHA). METHODS: We retrospectively analyzed results from in-house IFN-γ-release assays with HBHA (HBHA-IGRA) and rESAT-6 (rESAT-6-IGRA) performed during a 12-year period on serial blood samples (3 to 9) collected from 23 LTBI subjects in a low-TB incidence country. Both the kinetics of the absolute IFN-γ concentrations secreted in response to each antigen and the dynamics of HBHA/rESAT-6-induced IFN-γ concentrations ratios were examined. RESULTS: This analysis allowed the identification among the LTBI subjects of three major groups. Group A featured stable HBHA and rESAT-6-IGRA profiles with an HBHA/rESAT-6 ratio persistently higher than 1, and with high HBHA- and usually negative rESAT-6-IGRA responses throughout the study. Group B had changing HBHA/rESAT-6 ratios fluctuating from 0.0001 to 10,000, with both HBHA and rESAT-6 responses varying over time at least once during the follow-up. Group C was characterized by a progressive disappearance of all responses. CONCLUSIONS: By combining the measures of IFN-γ concentrations secreted in response to an early and a latency antigens, LTBI subjects can be stratified into different risk groups. We propose that disappearing responses indicate cure, that persistent responses to HBHA with HBHA/rESAT-6 ratios ≥ 1 represent stable LTBI subjects, whereas subjects with ratios varying from >1 to <1 should be closely monitored as they may represent the highest-risk group, as illustrated by a case report, and should therefore be prioritized for preventive treatment.

Nephrotic syndrome and renal failure as an unusual presentation of solid tumour.

Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among glomerulopathies, membranous nephropathy is preferentially associated with respiratory and gastrointestinal tract adenocarcinomas, whereas minimal change disease is most often seen in haematological malignancies. Though breast cancer is one of the most frequent malignancies in women, paraneoplastic glomerular disease is rarely observed. We describe the case of a 79-year-old female patient who presented with nephrotic syndrome and renal failure. Breast cancer was found. Pathological studies of kidney and breast biopsy revealed a minimal change disease and an infiltrating ductal carcinoma, respectively.