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NCT Number: NCT06327750

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.

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Key information

Conditions

End-stage Renal Disease Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Kidney Failure, Chronic Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Hemodialysis (DNa = PNa)

Device

High-flux hemodialysis with an expected zero diffusive sodium balance (DNa = PNa)

Hemodialysis (DNa<PNa)

Device

High-flux hemodialysis with expected diffusive sodium efflux (DNa<PNa, difference: 3 mmol/L)

Hemodialysis after isolated ultrafiltration (DNa=PNa)

Device

High-flux hemodialysis after isolated ultrafiltration with an expected zero diffusive sodium balance (DNa=PNa)

High volume hemodiafiltration (DNa=PNa)

Device

High volume hemodiafiltration with an expected zero diffusive sodium balance (DNa=PNa) Convection volume: ≥23L/session

High volume hemodiafiltration (DNa<PNa)

Device

High volume hemodiafiltration with expected diffusive sodium efflux (DNa<PNa, difference: 3 mmol/L) Convection volume: ≥23L/session

Primary outcomes

  1. Skin microcirculation

    Time frame: up to 20 weeks; assessed every 4 weeks before the last dialysis session of each treatment period (i.e. 5 times in total)

    Skin microcirculatory perfusion/vasoreactivity (arbitrary units) measured with a laser speckle contrast analysis (LASCA) perfusion imager

  2. Sequestered salt content (SSC)

    Time frame: up to 20 weeks; assessed every 4 weeks before the last dialysis session of each treatment period (i.e. 5 times in total)

    SSC measured with a 7 Tesla 23-Sodium MRI

Secondary outcomes

  1. Intradialytic hypotension

    Time frame: up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)

    A systolic blood pressure (SBP) ≤ 90 mmHg in patients with a pre-dialysis SBP < 160 mmHg and a SBP < 100 mmHg in patients with a pre-dialysis SBP ≥ 160 mmHg.

  2. Change in intradialytic blood pressure

    Time frame: up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)

    Change in systolic and diastolic blood pressure (mmHg) during one dialysis session

  3. Peridialytic blood pressure

    Time frame: up to 24 hours (=one interdialytic day): measured 3x/day every 4 weeks during the last interdialytic day of each treatment period (i.e. 5 times in total)

    Change in systolic and diastolic blood pressure (mmHg) between dialysis sessions

  4. Change in CK-MB

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker of cardiac damage, assessment in blood from arterial line of extracorporeal circuit

  5. Change in high sensitivity C-reactive protein (hs-CRP)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit

  6. Change in interleukin-6 receptor (IL-6R)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit

  7. Change in soluble CD163 (sCD163)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit

  8. Change in soluble intercellular adhesion molecule-1 (s-ICAM-1)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit

  9. Change in serum glycosaminoglycans

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit

  10. Change in syndecan-1

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit

  11. Change in vascular endothelial growth factor C (VEGF-C)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit

  12. Change in extracellular vesicles (EVs)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Marker for tissue-injury and inflammation, assessment in blood from arterial line of extracorporeal circuit

  13. Change in skin microcirculation

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Change in skin microcirculatory perfusion/vasoreactivity (arbitrary units) measured with a laser speckle contrast analysis (LASCA) perfusion imager during one dialysis session. This will be assessed in 5 patients only.

  14. Change in sequestered salt content (SSC)

    Time frame: up to 4 hours (=one dialysis treatment); measured before and immediately after the last dialysis session of each treatment period (i.e. 10 times in total)

    Change in SSC measured with a 7 Tesla 23-Sodium MRI during one dialysis session. This will be assessed in 5 patients only.

  15. modified Dialysis symptom index (mDSI)

    Time frame: up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period

    Standardized questionnaire for the evaluation of physical symptoms and recovery time in dialysis patients, consisting of 13 items. Participants rate the severity of each item on a 5-point likert scale, ranging from 0 ('not at all') to 4 ('very much'). Higher scores indicate a greater perceived severity of symptoms.

  16. Thirst distress scale (TDS)

    Time frame: up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period

    The thirst distress scale is a 6-item questionnaire that measures thirst distress on a scale from 1 to 5, where 1 corresponds to 'Strongly disagree' and 5 to 'Strongly agree'. Higher scores indicate greater perceived thirst distress.

  17. EQ Visual analogue scale (EQ VAS)

    Time frame: up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period

    The EQ VAS records the patients's self-rated health-related quality of life on a vertical visual analogue scale where 0 means 'the worst health you can imagine' and 100 means 'the best health you can imagine'. Higher scores indicate a better perceived health-related quality of life.

Study contacts

Contact information is provided by the study sponsor or research team.

Muriel PC Grooteman, MD PhD

CONTACT

[email protected]

+3120 566 5990

Sabrine Chaara, MD

CONTACT

[email protected]

+316463173499

Sponsors and collaborators

Lead sponsor

Amsterdam UMC, location VUmc

Other

Collaborators

  • B.Braun Avitum AG
  • Dutch Kidney Foundation
  • Niercentrum aan de Amstel

Registry information

Acronym: MIMOSA

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Mar 25, 2024
Registry last updated
Mar 25, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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