The Microcirculation, Dialysis Modality and Sequestered Salt

End-stage Renal Disease Clinical Trial

— MIMOSA  

Official title:

The Microcirculation, Dialysis Modality and Sequestered Salt

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06327750
• Other study ID #: NL83566.018.24
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: December 2027

Study information

• Verified date: March 2024
• Source: Amsterdam UMC, location VUmc
• Contact: Muriel PC Grooteman, MD PhD
• Phone: +3120 566 5990
• Email: mpc.grooteman[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 22
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End-stage Renal Disease
• Kidney Failure, Chronic

Intervention

Device:
• Hemodialysis (DNa = PNa)
High-flux hemodialysis with an expected zero diffusive sodium balance (DNa = PNa)
• Hemodialysis (DNa<PNa)
High-flux hemodialysis with expected diffusive sodium efflux (DNa<PNa, difference: 3 mmol/L)
• Hemodialysis after isolated ultrafiltration (DNa=PNa)
High-flux hemodialysis after isolated ultrafiltration with an expected zero diffusive sodium balance (DNa=PNa)
• High volume hemodiafiltration (DNa=PNa)
High volume hemodiafiltration with an expected zero diffusive sodium balance (DNa=PNa) Convection volume: =23L/session
• High volume hemodiafiltration (DNa<PNa)
High volume hemodiafiltration with expected diffusive sodium efflux (DNa<PNa, difference: 3 mmol/L) Convection volume: =23L/session

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	B.Braun Avitum AG, Dutch Kidney Foundation, Niercentrum aan de Amstel

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Skin microcirculation	Skin microcirculatory perfusion/vasoreactivity (arbitrary units) measured with a laser speckle contrast analysis (LASCA) perfusion imager	up to 20 weeks; assessed every 4 weeks before the last dialysis session of each treatment period (i.e. 5 times in total)
Primary	Sequestered salt content (SSC)	SSC measured with a 7 Tesla 23-Sodium MRI	up to 20 weeks; assessed every 4 weeks before the last dialysis session of each treatment period (i.e. 5 times in total)
Secondary	Intradialytic hypotension	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.	up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)
Secondary	Change in intradialytic blood pressure	Change in systolic and diastolic blood pressure (mmHg) during one dialysis session	up to 4 hours (=one dialysis treatment); assessed during all dialysis sessions (12 treatments per intervention, measured 4x/hour)
Secondary	Peridialytic blood pressure	Change in systolic and diastolic blood pressure (mmHg) between dialysis sessions	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)
Secondary	Change in CK-MB	Marker of cardiac damage, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in high sensitivity C-reactive protein (hs-CRP)	Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in interleukin-6 receptor (IL-6R)	Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in soluble CD163 (sCD163)	Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in soluble intercellular adhesion molecule-1 (s-ICAM-1)	Marker of inflammation, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in serum glycosaminoglycans	Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in syndecan-1	Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in vascular endothelial growth factor C (VEGF-C)	Marker related to sequestered sodium content, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in extracellular vesicles (EVs)	Marker for tissue-injury and inflammation, assessment in blood from arterial line of extracorporeal circuit	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)
Secondary	Change in skin microcirculation	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.	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)
Secondary	Change in sequestered salt content (SSC)	Change in SSC measured with a 7 Tesla 23-Sodium MRI during one dialysis session. This will be assessed in 5 patients only.	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)
Secondary	modified Dialysis symptom index (mDSI)	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.	up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period
Secondary	Thirst distress scale (TDS)	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.	up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period
Secondary	EQ Visual analogue scale (EQ VAS)	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.	up to 20 weeks; evaluated every 4 weeks, during/after the last dialysis session of each treatment period