Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study.

RATIONALE & OBJECTIVE: The EvoCit study was designed to evaluate performance of a heparin-grafted dialyzer during hemodialysis with and without systemic anticoagulation. STUDY DESIGN: Randomized, crossover, noninferiority trial. Noninferiority was defined as a difference of≤10% for the primary outcome. SETTING & PARTICIPANTS: Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions. INTERVENTIONS: Hemodialysis using a heparin-grafted dialyzer combined with a 1.0mmol/L citrate-enriched dialysate ("EvoCit") without systemic anticoagulation compared with hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("EvoHep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks. OUTCOMES: The primary end point was the difference in Kt/Vurea between EvoCit and EvoHep. Secondary end points were urea reduction ratio, middle molecule removal, treatment time, thrombin generation, and reduction in dialyzer blood compartment volume. RESULTS: The estimated difference in Kt/Vurea between EvoCit and EvoHep was-0.03 (95% CI, -0.06 to-0.007), establishing noninferiority with mean Kt/Vurea of 1.47±0.05 (SE) for EvoCit and 1.50±0.05 for EvoHep. Noninferiority was also established for reduction ratios of urea and ß2-microglobulin. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during EvoCit and no sessions during EvoHep. Effective treatment time was 236±5 minutes for EvoCit and 238±1 minutes for EvoHep. Thrombin generation was increased and there was greater reduction in dialyzer blood compartment volume after treatments with EvoCit compared with EvoHep. LIMITATIONS: The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated. CONCLUSIONS: EvoCit is noninferior to EvoHep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting, and greater thrombin generation TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03887468.

Risk for excessive anticoagulation during hemodialysis is associated with type of vascular access and bedside coagulation testing: Results of a cross-sectional study.

Background: Recommendations and practice patterns for heparin dosing during hemodialysis show substantial heterogeneity and are scantly supported by evidence. This study assessed the variability in unfractionated heparin (UFH) dosing during hemodialysis and its clinical and biological anticoagulatory effects, and identified explanatory factors of heparin dosing. Methods: Cross-sectional study assessing UFH dosing, coagulation tests - activated partial thromboplastin time (aPTT) and activated clotting time (ACT) before dialysis start, 1 h after start and at treatment end (4 h) - and measurement of residual blood compartment volume of used dialyzers. Results: 101 patients, 58% male, with a median dialysis vintage of 33 (6-71) months received hemodialysis using a total UFH dose of 9,306 ± 4,079 (range 3,000-23,050) IU/session. Use of a dialysis catheter (n = 56, 55%) was associated with a 1.4 times higher UFH dose (p < 0.001) irrespective of prior access function. aPTT increased significantly more than ACT both 1 h and 4 h after dialysis start, independent of the dialysis access used. 53% of patients with catheter access and ACT ratio < 1.5, 1 h after dialysis start had simultaneous aPTT ratios > 2.5. Similar findings were present at 1 h for patients with AVF/AVG and at dialysis end for catheter use. No clinically significant clotting of the extracorporeal circuit was noted during the studied sessions. Dialyzer's blood compartment volume was reduced with a median of 9% (6-20%) without significant effect of UFH dose, aPTT or ACT measurements and vascular access type. Conclusion: UFH dose adaptations based on ACT measurements frequently result in excessive anticoagulation according to aPTT results. Higher doses of UFH are used in patients with hemodialysis catheters without evidence that this reduces dialyzer clotting.

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.

Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes.

BACKGROUND: Patients with hereditary tumor syndromes undergo periodical magnetic resonance imaging (MRI) screening with Gadolinium contrast. Gadolinium accumulation has recently been described in the central nervous system after repeated administrations. The prevalence and rate of accumulation in different subgroups of patients are unknown. Neither are the mechanism nor clinical impact. This may cause uncertainty about the screening. To explore the prevalence and rate of Gadolinium accumulation in different subgroups, we retrospectively analyzed MRIs of patients with von Hippel-Lindau disease (VHL) and Tuberous Sclerosis Complex (TSC). METHODS: We determined the prevalence and rate of accumulation in the dentate nucleus and globus pallidus on unenhanced T1-weighted MRI from VHL and TSC patients. We compared the signal intensities of these regions to the signal intensity of the pons. We evaluated the impact of number of MRIs, kidney function and liver function on Gadolinium accumulation. RESULTS: Twenty eight VHL patients and 24 TSC patients were included. The prevalence of accumulation in the dentate nucleus and globus pallidus increased linearly according to number of Gadolinium enhanced MRIs and was higher in the VHL group (100%). A significant linear correlation between number of MRIs and increased signal intensity was observed in the VHL group. CONCLUSIONS: Gadolinium accumulation occurs in almost all patients undergoing contrast MRI screening after >5 MRIs. We advocate a screening protocol for patients with hereditary tumor syndromes that minimizes the Gadolinium dose. This can be accomplished by using a single administration to simultaneously screen for brain, spine and/or abdominal lesions, using an MRI protocol focused on either VHL- or TSC-specific lesions. Higher prevalence and rate of accumulation in VHL patients may be explained by the typical vascular leakage accompanying central nervous system hemangioblastomas.