Optimisation of Anticoagulation in Patients on Nocturnal Hemodialysis

This single centre, randomized cross-over study includes twenty stable chronic nocturnal hemodialysis patients with no coagulation disorder, active inflammation or chronic cumarin-derived medication.

Patients are randomized over 2 study arms. Each patient is dialyzed over 480min (at midweek) with 2 different settings: anticoagulation only at the dialysis start, and anticoagulation divided over two time points, i.e. dialysis start and halfway dialysis.

For each patient, the dialyzer, the dialysis mode (hemodialysis or hemodiafiltration) and the dialysis settings (blood flow, dialysate flow and substitution flow) are those as currently used by the patient during in-centre nocturnal dialysis.

To determine antiXa, blood samples are taken from the inlet dialysis line at the dialysis start (i.e. 5min after administration of the anticoagulant) and at 1h, 4h and 8h after dialysis start. During the session with 2 anticoagulant administrations, an extra blood sample is taken before as well as after the second anticoagulant administration.

Before the first test session, 1 blood sample is taken to determine antithrombin-III (AT-III).

In order to quantify dialyzer performance in terms of number of patent fibers, dialyzers are scanned after dialysis, using a glod standard non-invasive micro-CT technique.

Therefore, at the end of the dialysis session, a standard rinsing procedure of the hemodialyzer is performed using exact 300mL rinsing solution. Next, the hemodialyzer is dried using continuous positive pressure ventilation. Dialyzer fibre blocking is visualized in the dialyzer outlet potting using a 3D CT scanning technique on micrometer resolution. HECTOR is a High Energy CT scanner Optimized for Research, built by the Ghent University Centre for X-ray Tomography (UGCT) in collaboration with the UGCT spin-off company XRE (Gent, Belgium). In front of the X-ray source, the dialyzer is mounted vertically on a precision rotation stage, and radiographies were recorded over 360° with an angular interval of 0.15°. Scan conditions are optimized to maximize the signal-to-noise ratio based on the sample size and structure, and the scanner properties. The tube voltage is set at 80kV, at a power of 20 Watts, the maximal power that allowed imaging at a resolution of 25μm. A total of 2401 projections are recorded with 500ms exposure each, resulting in a total exposure time of 20 minutes. Acquired images at 0 (projection 1) and 360° (projection 2401) are compared to exclude movement of the hemodialyzer during the scanning process. Reconstruction of the raw projection data is performed with the Octopus Reconstruction software package, licensed by XRE23.

The non-blocked fibers are counted in the central cross-section of the dialyzer outlet potting in a computer-based way using the Fiji image processing toolkit of ImageJ analysis software (ImageJ 1.51H, NIH, Bethesda, USA), an open-source platform for biological-image analysis. By comparing the number of non-blocked fibers in used versus non-used dialyzers, the percentage of fiber blocking can be calculated.

By comparing the number of open fibers between the 2 test sessions (1 versus 2 anticoagulant administrations), the difference can objectively be scored for prolonged (nocturnal) dialysis.

Inclusion criteria

• 18 years or older
• experienced stable dialysis sessions during the last 4 weeks
• nocturnal in-centre hemodialysis
• well functioning vascular access

Exclusion criteria

• known coagulation disorder
• active inflammation
• malignancy
• no coumarin-derived medication