The Microcirculation, Dialysis Modality and Sequestered Salt

The aim of this clinical trial is to investigate the effect of 5 different dialysis treatments (combinations of dialysis mode and dialysis fluid sodium content) on the microcirculation (MC) and sequestered sodium content (SSC) in adult prevalent end-stage kidney disease (ESKD) patients treated with hemodialysis (HD) or hemodiafiltration (HDF). The main questions it aims to answer are:

1. What are the effects on the sequestered sodium content and microcirculation after 4 weeks of treatment with the following dialysis modes?

   * HDF with an expected zero diffusive sodium balance (Dialysate sodium concentration (DNa)= Plasma sodium concentration (PNa)) compared to
   * HDF with an expected diffusive sodium efflux (DNa \< PNa, difference 3 mmol/L) compared to
   * HD with an expected zero diffusive sodium balance (DNa = PNa) compared to
   * HD with an expected diffusive sodium efflux (DNa \< PNa, difference 3 mmol/L) compared to
   * Isolated ultrafiltration for 30 minutes followed by HD with an expected zero diffusive sodium balance (DNa = PNa)
2. Are the SSC and MC interrelated in this patient group?

This study is a randomized cross-over trial. Participants will be subjected to the abovementioned dialysis treatment modes in random order.

The life expectancy of patients with end-stage kidney disease (ESKD) is poor. Post-dilution online hemodiafiltration (HDF) is associated with a lower mortality than standard hemodialysis (HD), especially when a high convection volume is achieved (high-volume HDF; hvHDF). It is unclear, however, why (hv)HDF improves survival. Neither an increased clearance of middle molecular weight uremic toxins, nor an improved bio-incompatibility can explain the difference. As the effects are already observed within 2.5 years, recovery of a functional disorder is more likely than restoration of structural alterations. The recuperation of vascular dysfunction may be the missing piece of the puzzle. Previous literature showed (1) that the microcirculation (MC) is severely disturbed in dialysis patients, (2) excess sodium can bind to glycosaminoglycans in the interstitium and in the glycocalyx of blood vessels without commensurate water retention (sequestered sodium content \[SSC\]) and (3) that in patients with non-dialysis dependent chronic kidney disease, a disturbed SSC is related to capillary rarefaction and dysfunction. Therefore, the present study aims to assess the influences of both the modality (HD and HDF) and the dialysate sodium concentration (DNa) on the SSC and the MC.

Therefore the following hypotheses will be evaluated: (1, 2) treatment with hvHDF improves the SSC and MC, if compared to HD; (3, 4) disorders of the SSC and the MC are influenced by differences between the dialysate sodium \[DNa\] and plasma sodium \[PNa\] concentrations; (5) SSC and MC are interrelated in this patient group.

Eligibility Criteria:
Inclusion Criteria:

* Age ≥18 years
* Treatment with HD or HDF 3 x per week during at least 4 hours for at least 3 months
* Blood flow rate feasiblity of ≥350 ml/min
* Residual diuresis \<200 ml/day
* Plasma Na before dialysis 137-145 mmol/L at baseline
* spKt/Vurea ≥ 1.2
* Ability to understand study procedures and willingness to provide informed consent

Exclusion Criteria:

* Severe incompliance to dialysis procedure and accompanying prescriptions, especially frequency and duration of dialysis treatment
* Life expectancy \< 3 months due to non-renal disease
* Expected transplantation within 6 months
* Access recirculation \> 10%
* Participation in another clinical intervention trial
* Metal implants (e.g. implantable cardioverter defibrillators)
* Severe obesity (MRI Ø 60 cm ≈ abdominal circumference ≤ 188 cm)
* Claustrophobia