Hemodynamic Effects of Low vs. High Dialysate Temperature or Bicarbonate Concentration in Chronic Hemodialysis Patients
Phase: NA
Conditions: End Stage Renal Disease on Dialysis
Sponsor: University of Aarhus

Protocol version 2.0 (23-06-2021) 
 
 
1 
HEMODYNAMIC EFFECTS OF LOW VS. HIGH DIALYSATE 
TEMPERATURE OR BICARBONATE CONCENTRATION IN 
CHRONIC HEMODIALYSIS PATIENTS (TURBO) 
Research team and contact information 
Research team 
Christian Daugaard Peters, Senior registrar, Post doc, PhD 
(Principal investigator) 
Jonas Schandorph Kaalund Jensen, Medical student 
Ina Ejsing Hunnerup Jørgensen, Medical student 
Jens Kristian Dam Jensen, Consultant, PhD 
Niels Henrik Buus, Professor, Consultant, Med.Sc.D, PhD 
 
 
Contact information 
Department of Renal Medicine 
Aarhus University Hospital 
Palle Juul-Jensens Boulevard 99 
8200 Aarhus N 
Denmark 
 
 
Background 
Intradialytic hypotension (IDH) is a common complication of hemodialysis (HD) and is considered 
one of the most frequent complications with a prevalence between 10-12% depending on the 
definition of IDH (1). IDH has been associated with inefficient dialysis (2), vascular access 
thrombosis (3) and mortality (4,5).  
Orthostatic hypotension (OH) is another common complication in HD with a prevalence around 42% 
in patients initiating HD treatment (6). OH is significantly associated with worse outcome in HD 
patients in terms of an increased two-year mortality (4) and increased risk of all-cause death (6). 
 
Understanding the mechanisms underlying IDH and OH has the potential to optimize HD treatment, 
in order to minimize the occurrence of IDH and OH, potentially improving not only patient mortality 
and morbidity but also the everyday comfort of chronic HD patients when receiving dialysis 
treatment. 
 
This study will investigate the hemodynamic effect of alterations in dialysate bicarbonate and 
dialysate temperature. Due to the different nature of the two interventions, they will be addressed 
separately in the following. 
 
Dialysate temperature 
Several clinical studies have examined the effect of low temperature dialysate (LTD) on IDH, but 
only few have examined the hemodynamic response in detail with intradialytic measurements of 
cardiac output (CO), central blood volume (CBV) and total peripheral resistance (TPR) (7–14). 
Generally, the studies confirm a blood pressure (BP) stabilizing effect of LTD, but diverse results are 

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found on changes in CO, CBV and TPR. Some studies found greater increase in TPR during dialysis 
with LTD compared to a higher dialysate temperature (8,9,11,14). Other studies found that 
intradialytic CBV (7,12) and CO (12) improved considerably with LTD. 
To the best of our knowledge only one study (14) have examined OH in relation to use of LTD, but 
not with detailed intradialytic hemodynamic measurements. The study showed that both supine and 
upright MAP were significantly lower after dialysis with a dialysate temperature of 37°C compared 
to a dialysate temperature of 35°C. Furthermore, the increase in TPR was greater during dialysis with 
LTD. 
 
Dialysate bicarbonate 
Few studies have investigated the effect of dialysate bicarbonate (DB) concentration on intradialytic 
hemodynamics and results have been conflicting. Lower DB (from 32 to 26 mmol/L or a reduction 
of 6 mmol/L, respectively) was in two cross-over studies (15,16) shown to increase systolic BP by 
approximately 5 mmHg, whereas a third study reported no significant effect on BP (17). One of these 
studies also found an increase in TPR with lower DB (16). IDH has been associated with lower DB 
in one of the previously mentioned cross-over studies (15), but this association was not found by 
Gabutti et al in 2005 (17) or in larger observational studies (17–19). Manipulation of DB inevitably 
affects plasma pH of the patient during dialysis. Thus, if pH decreases with DB-induced acidosis, 
hydrogen ions displace cations such as calcium from protein binding sites. DB-induced alkalosis on 
the other hand increases pH, which promotes increased protein binding, which decreases free cation 
levels. At the same time, intracellular sequestration of potassium at high pH levels has also been 
speculated to lower plasma potassium levels (20). Consequently, by changing DB a range of 
electrolytes including calcium are potentially affected which could impact neuromuscular function 
and thereby intradialytic hemodynamic parameters and the frequency of IDH and OH (17,21–26).  
 
Summary 
To elucidate the role of dialysate temperature and bicarbonate on hemodynamic parameters, plasma 
pH and electrolytes that potentially mediate this effect, we wish to conduct a single-blinded, 
randomized, controlled, crossover study, specifically examining the effects of  
• A fixed LTD of 35°C compared to a fixed dialysate temperature of 37°C.  
• A low DB concentration of 30 mmol/L compared to a high DB concentration of 38 mmol/L. 
 
Hypotheses and endpoints 
Hypotheses 
We hypothesize that hemodialysis or hemodiafiltration (HdF) sessions with a decreased dialysate 
temperature (35°C vs. 37°C) or decreased DB concentration (30 mmol/L vs. 38 mmol/L) will have 
the following effects:  
• 
An increase in systolic blood pressure (SBP), mean arterial blood pressure (MAP) and 
orthostatic blood pressure (OBP). 
• 
An increase in one or more of the following: TPR, CO, CBV, stroke volume (SV) and/or heart 
rate (HR).  
• 
A decrease in the frequency of IDH and OH. 

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Primary and secondary endpoints 
The primary endpoint for the study is BP (SBP, MAP and OBP)  
 
Secondary endpoints are:  
• 
Hemodynamic parameters: TPR, CO, CBV, SV and HR 
• 
Electrolytes: Calcium, potassium and magnesium  
• 
Frequency of IDH and OH 
 
All endpoints are assessed as the difference between within-treatment changes during HD or HdF 
sessions when manipulating either dialysate temperature (35°C vs. 37°C) or DB concentration (30 
mmol/L vs. 38 mmol/L). 
 
Methodology 
Study design 
The study will be a single-blinded, randomized, controlled, crossover study with each participant 
being his or her own control (Figure 1). Participants will be blinded to the intervention and the order 
of the interventions will be random.  
Participants will be randomized using bloc randomization. We will create two blocs (sequence 1 
(Green) and sequence 2 (Yellow)) with 8 participants in each. The four dialysis sessions will be 
conducted on the same weekday each week, which results in a 1-week wash-out period with standard 
dialysis treatment between interventions.  
 
Practical considerations 
Dialysis machines, filters, and dialysate composition 
Dialysis console Fresenius 5008F (Fresenius Medical Care, Bad Homburg, Germany) and HD or HdF 
filters regularly used for treatment of the patient will be used in all dialysis sessions. 
The standard dialysate prescribed for each individual patient will be used in all dialysis sessions 
thereby maintaining similar composition regarding electrolytes such as sodium, potassium, calcium, 
magnesium and chloride. Bicarbonate concentration will only be adjusted in the sessions 
investigating low (30 mmol/L) and high (38 mmol/L) DB concentration, respectively. Dialysate will 
be prepared on-line by the dialysis machine. Blood flow rate and dialysate flow rate will be kept as 
usual and will remain equal in all sessions regardless of intervention. Ultrafiltration rate will be kept 
constant and equal in the two dialysis sessions. The same applies for the volume of substitution fluid 
in HdF. 
 
Intradialytic restrictions regarding participants and their medications 
In order to standardize intradialytic conditions as much as possible and in order to avoid splanchnic 
redistribution of blood volume, the participants will be asked not to eat, drink, or sleep during the 
dialysis session. Throughout the study period medications affecting hemodynamics (e.g. blood 
pressure medications) will not be changed. Patients are encouraged not to deviate from their regular 
schedule in terms of timing or dosage of medication.  

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Figure 1: Study design 

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BP measurements 
We will use the same automatic and validated BP device for all BP measurements (see Figure 2). The 
BP cuff will be chosen according to arm size and placed on the non-AV-fistula arm. The cuff should 
be positioned at the level of the heart, with the back and arm supported to avoid muscle contraction 
and isometric exercise-dependent increases in BP. Patient should be lying comfortably in a supine 
position for 5 minutes before beginning BP-measurements. Three BP measurements are recorded 1–
2 min apart, and additional measurements only if the first two readings differ by >10 mmHg. BP is 
recorded as the average of the last two BP readings. The patient is not allowed to talk during the 
measurements. 
 
OBP measurements 
The patient will rest in bed for 5 minutes in the supine position, then HR (beats/min.) and BP (mmHg) 
are measured. The patient will then be asked to stand up beside the bed. BP and HR will be measured 
repeatedly with a 1-minute interval while standing for a minimum of 3 minutes. If BP declines at the 
third minute measurement, measurements can be continued for up to 10 minutes. The lowest BP while 
standing will be noted as the result for the orthostatic BP test.  
 
Orthostatic hypotension (OH) 
OH is defined as a reduction in SBP of at least 20 mmHg or in DBP of at least 10 mmHg within 3 
minutes of standing (27). 
 
Intradialytic hypotension (IDH) 
IDH is defined as a decrease in systolic BP ≥20 mmHg or a decrease in MAP ≥10 mmHg associated 
with clinical events/symptoms (e.g. muscle cramps, abdominal discomfort, nausea or vomiting, 
dizziness or fainting, restlessness or anxiety, yawning or signing) and/or need for intradialytic 
interventions (Trendelenburg positioning, fluid administration, reduction in ultrafiltration rate, 
reduction of blood flow rate) or dialysis treatment cessation (28). 
 
Before dialysis: 
As the participant arrives in the hemodialysis clinic, he/she will be weighed (kg) with usual clothing. 
He/she will be followed to a bed and asked to lie down in a supine position and then a standard 12-
lead electrocardiogram (ECG) is recorded. Followed by a bioimpedance measurement using the Body 
Composition Monitor (BCM, Fresenius Medical Care) for determination of fluid status and body 
composition. Subsequently an orthostatic BP test will be performed. 
 
The nurse will then prepare the patient for dialysis treatment and will manage insertion of dialysis 
needles in the AV-fistula. Furthermore, the nurse will connect the extra tubes needed for the 
Transonic device. Fragmin (standard dose) is administrated, and the dialysate temperature/dialysate 
bicarbonate is regulated according to randomization. 
Before the dialysis session is started blood samples on infectious parameters and magnesium and an 
arterial blood gas will be drawn from the arterial cannula. 
 

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Time course - from the participant arrives to the participant leaves the dialysis clinic 
 
Figure 2   An overview of the time course. It illustrates what will occur before, during and after dialysis.  
 
During dialysis: 
CO will be obtained by a previously validated ultrasound dilution technique using Hemodialysis 
Monitor HD03, Flow-QC tubing sets, and clip-on flow/dilution sensors from Transonic Systems Inc., 
Ithaca, NY, USA (29–32). The ultrasound sensors will be positioned on the arterial and venous Flow-
QC tubing set using standard ultrasound gel to secure good contact. Access recirculation in the AV-
fistula can invalidate CO-measurements. A built-in recirculation protocol will be used to check for 
access recirculation using injection of 10 mL isotonic saline into the venous blood line prior to the 
first CO-measurement. If recirculation is detected the dialysis needles will most likely be reinserted. 
CO will be measured in duplicate by injecting a bolus of 30 mL 37°C isotonic saline into the venous 
blood line within 5 seconds. If results deviate more than 15% a third measurement will be done. The 
mean of the two closest recordings will serve as the result. With the Transonic device intradialytic 
hemodynamic parameters are obtained at 10, 70, 130, 190, and 230 minutes. Patients will be lying in 
a supine position with the head elevated 20 degrees. Before each CO measurement HR and BP will  
be measured.  
 
Following the same time pattern as the Transonic measurements an arterial blood gas will be drawn 
from the arterial cannula.  
 
Changes in relative blood volume (RBV) (%) during dialysis are monitored continuously by the 
module (blood volume monitor, Fresenius Medical Care) incorporated in the dialysis machine, which 
measures changes in RBV by measuring changes in hemoconcentration markers (hematocrit, 
hemoglobin or total blood protein concentration). Cumulative ultrafiltration volume (mL) is 
registered every 15 minutes during dialysis. Temperature and energy transfer in the arterial and 

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venous tubing will be recorded continuously by the blood temperature monitor mounted on the 
dialysis console (BTM, Fresenius Medical Care).  
 
Generally, if a dialysis session is interrupted the participant will be given a replacement day on a 
corresponding weekday. In the event of IDH we will obtain a BP measurement and subsequently, the 
nurse will try to stabilize the patient with the necessary interventions.  
 
After dialysis:  
After dialysis an arterial blood gas will be taken from the arterial cannula for determination of the 
same parameters as before dialysis. Furthermore, a blood sample on magnesium will be drawn. 
 
The hemodialysis nurse will stop the dialysis and remove the dialysis needles when the session is 
finished. Patients usually stay 10 minutes after removal of dialysis needles to ensure 
hemostasis/minimize the risk of bleeding from the AV-fistula. This time will be utilized for an OBP 
measurement, which will follow the same method as before dialysis. Lastly, the patient will be 
weighed and leaves the clinic. 
 
Data from the dialysis session will be extracted from electronic patient journal, Therapy Data 
Management System (TDMS, Fresenius Medical Care) and Transonic HD03 Administrative 
Software (Transonic Systems Inc, Ithaca, NY). The mean arterial blood pressure (MAP), total 
peripheral resistance (TPR), and stroke volume (SV) are derived by the following equations: 
MAP = diastolic BP + 1/3 x (systolic BP – diastolic BP) 
CO = SV x HR = MAP/TPR 
 
Central blood volume (CBV) is defined as the volume of blood in the heart, lungs and great vessels 
and is estimated with the Transonic device based on the CO measurement as previously described 
(29).  
 
Dialytic Kt/V urea will be estimated by using Daugirdas formula (33) and urea reduction ratio will 
be calculated.  
 
Dialysis sessions are expected to last 30 minutes longer than usual, and patients will be informed of 
this before agreeing to participate.  
 
Statistical considerations 
Statistical analysis 
Within-treatment changes in hemodynamics and plasma concentrations of solutes will be calculated 
as differences (delta values), whereas between intervention comparisons (control vs. intervention) are 
performed by calculating the difference between within-treatment changes (“delta-delta values”). A 
two-tailed, paired Student’s t-test with no difference between the two treatments as the null 
hypothesis will be used to compare the two interventions. Statistical significance (α - level) will be 
set to 0.05. The paired t-tests require data to conform to a normal distribution. If this is not the case, 

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a logarithmic transformation of data can be performed to achieve a normal distribution. Alternatively, 
a non-parametric test (Wilcoxon Signed Rank test) can be performed to compare changes in relevant 
delta-values between the two groups.  
 
Power and sample size 
For estimation of standard deviation (SD) we used SBP measurements obtained before and after 
dialysis from 30 randomly selected patients undergoing HD or HdF treatment in the Dialysis Clinic 
at Aarhus University Hospital. Two treatment sessions were analyzed for each patient. The within 
treatment changes in SBP and mean differences between within-treatment changes in SBP (delta-
delta values) and corresponding SD’s were calculated, which yielded SD = 23 mmHg for the 
difference between within-treatment changes in SBP. This SD reflects non-standardized conditions 
in terms of dialysis treatment settings and BP-measurements in randomly selected patients not 
meeting the strict in-/exclusion criteria of the present study. Therefore, assuming a lower SD under 
standardized conditions we decided that SD = 12 mmHg was a reasonable estimate for the present 
study. Sample size calculation with Stata/IC 16.1 (StataCorp, 4905 Lakeway Dr, College Station, TX 
77845, USA) using analysis for a one-sample mean test (t-test), assuming a minimal detectable 
difference in means (mean difference between the two within-treatment changes in systolic BP) = 10 
mmHg; SD = 12 mmHg; two-sided significance level (alpha) = 0.05; power=0.80 resulted in 14 
participants. However, to account for dropout of two participants, a sample size of 16 was chosen.  
 
Study participants  
Participants will be recruited from the maintenance HD and HdF population associated with the 
Department of Renal Medicine at Aarhus University Hospital in Denmark. These include the Dialysis 
Clinic at Aarhus University Hospital as the main hub and satellite dialysis clinics in Randers and 
Horsens. Inclusion- and exclusion criteria are listed below in table 1 and table 2, respectively. 
 
 
Table 1   Inclusion criteria 
 

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Table 2   Exclusion criteria 
 
Risks and side effects 
Dialysis nurses will oversee the dialysis sessions and will connect the extra tubes needed for 
Transonic measurements. Saline injections are administered via dedicated injection ports for isotonic 
saline provided with the Transonic tubing set or via the dialysis machine using sterile technique after 
thorough training. If any unexpected events occur the dialysis nurse will intervene, and the principal 
investigator can be contacted if necessary.  
 
Manipulation of DB is not considered to induce any significant side-effects for the participants apart 
from what is commonly seen following a standard dialysis session with HD/HdF. Accordingly, 
lowering of DB may induce a slight increase in BP and a slight decrease in postdialytic pH compared 
to standard conditions. Since these changes are transient, they are not expected to cause any 
detrimental long-term side-effects for the participants, as demonstrated by previous trials using 
similar interventions (15–17). 
 
Participants might feel slightly discomfortable during intervention with LTD in terms of cold 
sensation or related symptoms (10), but could on the other hand also feel less fatigue and more 
energetic according to previous studies examining LTD (34,35).  
 
 
Participant exclusion and discontinuation of the study 
Should any serious known or unknown side effects or complications occur during the study, the study 
session will be discontinued, and the participant will receive treatment from a dialysis nurse or a 
medical doctor if deemed necessary. Following this, the investigators of the study in consultation 
with the patient will decide if the patients is to be excluded from the study or offered a replacement 
session on a corresponding weekday.  
If blood samples obtained on a given study session show signs of infection, the data obtained in this 
study session will be deemed invalid and will not be used in the study. Strong suspicion of infection 
will be handled as per usual in the hospital setting and can potentially lead to hospitalization for 
further investigation. Once the infectious state has receded, the patient can continue in the study via 

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a replacement day on a corresponding weekday. In the case of protracted illness or hospitalization, 
the patient will be excluded from the study.   
 
Blood sampling and handling of biological material  
Eleven blood samples will be taken from the arterial blood line via the AV-cannula used for dialysis 
treatment. Four of the samples will be regular blood samples of 3-4 mL, whereas 7 of the samples 
will be arterial blood gases of 1 mL. Thus, per session 22 mL blood per participant is collected which 
adds up to a total of 88 mL for the entire study period. The purpose of this is to determine several 
essential parameters: 
• 
Electrolytes such as calcium, magnesium, and potassium 
• 
Acid-base status: pH, standard bicarbonate, standard base excess 
• 
Hemoglobin, hematocrit 
• 
Urea for the determination of Kt/V and URR.  
• 
White cell count and C-reactive protein in the first blood sample in order to confirm the 
absence of infection 
 
All blood samples will be transferred to the laboratory according to standard routine and analyzed 
according to current clinical standards at Department of Clinical Biochemistry, Aarhus University 
Hospital or local Department of Clinical Biochemistry normally servicing our satellite dialysis clinics 
in Randers and Horsens. Blood gas tests are analyzed using ABL blood gas analyzer (Radiometer, 
Radiometer Medical ApS, Brønshøj Denmark). All blood samples will be destroyed after analysis. 
No samples will be stored in a biobank.   
 
Handling of personal information in the study 
Information from patient records 
For the purpose of recruitment, patient information regarding the inclusion- and exclusion criteria 
mentioned in table 1 and table 2 will be retrieved and assessed from the electronic medical record 
(MidtEPJ). Information retrieved before consent from patients only concerns the inclusion- and 
exclusion criteria and is fully contingent upon approval by the local ethics committee in Region 
Midtjylland (VEK) and authorization by the management of the Department of Renal Medicine, 
Aarhus University Hospital.  
Following informed consent from participants, the results from blood samples taken during the study 
will be retrieved from the electronic medical record. In addition to this, intradialytic parameters such 
as Kt/V, blood flow rate, dialysate flow rate, ultrafiltration rate, cumulative ultrafiltration volume and 
relative blood volume are obtained from the Therapy Data Management System (Fresenius Medical 
Care) software, which is routinely used in the dialysis unit at the Department of Renal Medicine, 
Aarhus University Hospital.  
 
The informed consent of study participants will grant investigators, potential trial sponsors and their 
representatives as well as any control authority direct access to obtain information in the patients’ 
medical records etc. including the electronic medical record in order to obtain information about the 
participant’s health conditions necessary for the execution of the study and for the purpose of control, 

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including self-regulation, quality control and monitoring, that the aforementioned parties are obliged 
to perform. 
 
Personal information 
The 
study 
will 
comply 
with 
The 
General 
Data 
Protection 
Regulation 
(GDPR) 
(Databeskyttelsesforordningen) and the Danish Data Protection Law (Databeskyttelsesloven).  
The Central Denmark Region (Region Midtjylland) will be data controller and the present study will 
be reported to The Central Denmark Region (Region Midtjylland) by the principal investigator (Intern 
fortegnelse over forskningsprojekter med Region Midtjylland som dataansvarlig). 
The personal information of participants will be protected according to “Sundhedsloven”. All study-
related data will be coded and saved in an electronic case report form (CRF). All potentially 
identifiable records of the participants are confidential and will not be made publicly available. Only 
the number assigned to each participant is registered in the CRF. Data is stored in anonymized form 
for a minimum of 5 years after the project has been completed in accordance with the Danish Data 
Protection Agency's guidelines. 
 
Financial aspects 
The project is a result of a shared initiative between medical students Ina Ejsing Hunnerup Jørgensen 
and Jonas Schandorph Kaalund Jensen at Aarhus University and medical doctors at the Department 
of Renal Medicine, Aarhus University Hospital Jens Kristian Dam Jensen, Christian Daugaard Peters 
and Niels Henrik Buus. The study has no association with any private corporations, and the 
investigative team have no financial interests in the study.  
Potential expenses of the study will be covered by the Dialysis Clinic, Department of Renal Medicine, 
Aarhus University Hospital with a potential for additional funding via public and private foundations. 
The latter includes expenses associated with biochemical analyses, publication of the study, travel 
expenses and congressional presentations.   
 
Possible compensation to study participants 
Participants will not be financially compensated for their participation.  
 
Recruitment of participants and informed consent 
Selection, initial contact and written material 
Eligible patients will be selected by reading through the electronic patients records of maintenance 
HD or HdF patients at the Department of Renal Medicine, Aarhus University Hospital and associated 
satellite clinics and filtering out patients that do not meet the above-described inclusion- and 
exclusion criteria. This will only happen after approval by the local ethics committee (De 
Videnskabsetiske Komitéer for Region Midtjylland) and the authorization and disclosure of the 
management of the Department of Renal Medicine, Aarhus University Hospital.  
Initial contact will happen while the selected patients are undergoing regular maintenance HD or HdF 
therapy at the Dialysis Clinic, Aarhus University Hospital and will be done by a member of the 
scientific team together with a dialysis nurse. Patients will receive a brief introduction to the study 

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and will be asked to consider participating, after which they will receive an invitation to a subsequent 
meeting at Aarhus University Hospital. Participants will be informed of their right to bring along a 
companion to the meeting and this will also be evident in the written material given to participants at 
initial contact, provided that patients express an interest in participating in the study. The written 
material handed out includes patient information(“Deltagerinformation”) which describes the project 
in layman terms and a pamphlet (“Forsøgspersoners rettigheder i et sundhedsvidenskabeligt 
forskningsprojekt”) on general participants rights in medical research projects (36).  
 
Informative meeting and consent 
The informative meeting will take place after initial contact and will be held by one of the 
investigators of the scientific team (a medical student or a medical doctor) within approximately 1 
week after initial contact. The patient is offered a choice between a telephone call or a private talk in 
a separate room to ensure the privacy of the conversation. Patients are advised to discuss participation 
with their relatives and can always be assisted by a person of their own choice for the informative 
meeting and are also advised about this possibility. The meeting will most likely take place in relation 
to the regularly scheduled dialysis treatments in the Dialysis Clinic. Participants will be asked for 
written consent at their next scheduled dialysis session, thereby securing a minimum of 24 hours to 
reflect on participation in the study prior to enrollment. Participants will be informed that they can 
withdraw from the study at any time if they should wish so, without this having any effect on their 
future treatment at the hospital.  
 
Scientific research team 
• 
Christian Daugaard Peters, Senior registrar, Post doc, PhD (Principal investigator) 
• 
Jonas Schandorph Kaalund Jensen, Medical student  
• 
Ina Ejsing Hunnerup Jørgensen, Medical student  
• 
Jens Kristian Dam Jensen, Consultant, PhD  
• 
Niels Henrik Buus, Professor, Consultant, Med.Sc.D, PhD  
• 
Nurses from the Dialysis Clinic at Aarhus University Hospital or affiliated satellite units in 
Horsens and Randers and lab technicians from the Research lab affiliated with Department of 
Renal Medicine 
 
Time plan and publication of results 
The study will begin in July 2021, and it is expected to end by the end of January 2022. 
Regardless of outcome, whether positive, negative or inconclusive, results will be published in 
international peer-reviewed journals. The study will also be registered at www.clinicaltrials.gov or 
www.clinicaltrialsregister.eu    
 
Perspectives 
The study is expected to provide valuable insights into the hemodynamic effects of changes in 
dialysate bicarbonate and dialysate temperature. This knowledge will potentially help clinicians when 
prescribing dialysis in order to alleviate patient discomfort and common side effects to dialysis 

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treatment such as IDH and OH. Ultimately, improvements in intradialytic hemodynamics may reduce 
morbidity and mortality for maintenance HD or HdF patients. 
 
Research ethics 
The study will be performed in accordance with the Helsinki Declaration per 2013. Patient autonomy 
and integrity will be respected, and identities will be protected and remain confidential in the 
publication of the study. Participants will only be included after informed consent is obtained by 
means of a written, signed and dated informed consent form. Moreover, participants will be informed 
that they can withdraw from the study at any time without consequences.  
 
The LTD may cause slight discomfort such as cold sensations, whereas low dialysate bicarbonate 
potentially may cause brief transitory shifts in the plasma pH of patients. However, none of these side 
effects are considered unsafe, harmful or unpleasant enough to give serious cause for concern for the 
health and wellbeing of the participants. Based on the non-harmful nature of the study and the 
potential therapeutic gain for HD or HdF patients worldwide, we, therefore, consider this study to be 
ethically sound. 
 
Insurance and compensation claims 
Should study participants, contrary to expectation, be harmed or injured during the study, they will 
be covered by the publicly funded compensation (“Patienterstatningen”).  
 
 

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