Hemodynamic effects of low versus high dialysate temperature in hemodialysis patients: a single-blinded, randomised, cross-over study

Hemodynamic effects of low versus high dialysate temperature in hemodialysis patients: a single-blinded, randomised, cross-over study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Hemodynamic effects of low versus high dialysate temperature in hemodialysis patients: a single-blinded, randomised, cross-over study Ina Ejsing Hunnerup Jørgensen, Jonas Schandorph Kaalund Jensen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7251357/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Cooling of the dialysate may improve intradialytic hemodynamics. This study compared low dialysate temperature (LDT) of 35°C with high dialysate temperature (HDT) of 37°C (standard) in terms of blood pressure (BP), intradialytic hemodynamics, and orthostatic BP. Methods In a single-blind, randomised, controlled, crossover study fourteen hemodialysis (HD) patients underwent a 4-h HD session with LDT (35°C) or HDT (37°C) separated by a 1- week interval. BP was monitored throughout HD. Intradialytic hemodynamics were assessed with ultrasound dilution technique (Transonic). Orthostatic BP was measured pre- and postHD. Results Ultrafiltration (mean with 95% confidence interval) was similar (LDT: 2.6(2.3;2.9) vs HDT: 2.5(2.0;3.1) liters). Arterial line temperature as a marker of body temperature remained stable with LDT but increased with HDT (mean change LDT: 0.0(-0.2;0.1) vs. HDT: 0.4(0.2;0.6)°C) with a mean between intervention difference of -0.4(-0.6;-0.3)°C. BP remained relatively stable on LDT, whereas HDT caused a significantly larger fall in systolic BP. The mean (± SD) fall in intradialytic systolic BP (PreHD vs. lowest intradialytic) was 20.3 ± 10.5 mmHg (HDT) and 9.6 ± 8.8 mmHg (LDT) with a mean between intervention difference of 10.7(3.2; 17.9) mmHg. LDT caused a significantly lower intradialytic heart rate which by the end of dialysis (after 230 minutes) on average was − 6.6(-13.0;-0.2) beats/min lower than HDT. Overall, the intradialytic hemodynamic response was similar except for a trend towards higher peripheral resistance and central blood volume with LDT. There was a significantly greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between interventions and the frequency of orthostatic hypotension postHD was also similar (HDT: 54% and LDT: 43%; P = 0.57). Conclusion Cooler vs. standard dialysate temperature resulted in significantly higher intradialytic BP but had no significant impact on orthostatic BP response postHD. Trial registration: The study was registered at ClinicalTrials.gov where the full study protocol is available (NCT05052151). Registration date was 26/08 2021. Blood pressure chronic renal failure dialysis temperature hemodynamics Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background The optimal hemodialysis (HD) dialysate temperature is not known. HD is typically performed by use of a standard dialysate temperature of 36.5°C or 37.0°C for all patients, although the reason for this choice is not entirely clear[ 1 ]. Cooler dialysate (< 36.5°) could have potential cardiovascular benefits including higher intradialytic blood pressure (BP)[ 2 , 3 ] and less cardiac[ 4 , 5 ] and cerebral injury[ 6 ]. With standard HD dialysate temperatures (≥37°C), core temperature increases despite net energy loss via the extracorporeal system[ 7 – 9 ]. It may be partly due to reduced heat loss from the skin resulting from vasoconstriction in response to blood volume reduction, but the pathophysiology is not fully clarified[ 1 , 10 ]. Low dialysate temperature (LDT) typically referred to as cooling of the dialysate or isothermic dialysis with temperature-controlled feedback can counteract the increase in body temperature. Studies have shown that use of LDT (in most studies 35°C) was associated with improved reactivity of peripheral resistance and capacitance vessels[ 11 ], increased myocardial contractility[ 12 ], reduced BP decline and lower risk of intradialytic hypotension (IDH) compared with a high dialysate temperature (HDT) of 37–37.5°C[ 3 ]. However, LDT could also induce a larger reduction in blood volume because of reduced refill from the interstitium due to peripheral vasoconstriction[ 13 , 14 ] and cause shivering as an unpleasant side-effect[ 3 , 10 ]. Orthostatic hypotension is highly prevalent in HD patients[ 15 ] and linked with an increased risk of falls and death[ 16 ], in line with findings in the general population[ 17 ]. Despite the obvious clinical relevance, only one previous study examined the effect of LDT on orthostatic BP and reported higher standing BP after LDT[ 18 ]. The aim of this study was to perform a detailed comparison of HD treatments with HDT and LDT in terms of BP, intradialytic hemodynamic parameters, and orthostatic BP response. We hypothesized that LDT of 35°C versus HDT of 37°C (standard) could result in higher BP, more stable intradialytic hemodynamics, and decreased frequency of orthostatic hypotension. Materials and Methods Study design The study was a single-blinded, randomised, cross-over study. Each participant attended two dialysis sessions: one with LDT of 35°C and one with HDT of 37°C. All other parameters including dialysate composition and dialysis membrane were kept unchanged. The sessions were separated with a one-week washout period with participants attending their usual HD treatment on the other weekdays. A Fresenius 5008 (Fresenius Medical Care, Bad Homburg, Germany) dialysis machine with a built-in monitor for arterial blood line temperature (BTM) reflecting central body temperature was used in all sessions. The order of the two interventions was performed by a built-in randomization module in REDCap (Research Electronic Data Capture (hosted at Clinical Trial Unit, Department of Clinical Medicine, Aarhus University[ 19 , 20 ]. The study was registered at ClinicalTrials.gov where the full study protocol is available (NCT05052151). Blood sampling and bioimpedance methodology has previously been published[ 21 ] but is also described in the Supplementary material. Study population HD patients were recruited from Aarhus University Hospital and Randers Regional Hospital from August-December 2021. Inclusion and exclusion criteria are given in the Supplementary material. Blood pressure, heart rate and orthostatic BP measurements A validated BP device (Microlife BP B2 Basic BP monitor, AG Swiss Corporation, Switzerland)[ 22 ] with a fitting cuff placed on the non-AV-fistula arm was used for all measurements. Supine BP and heart rate were measured approximately 10 min before (preHD) dialysis, 5 times during (10, 70,130, 190 and 230 min) dialysis and 10 min after dialysis (postHD). Prior to measurements each participant rested for 5 minutes, whereupon two recording were made. Additional measurements were made if the difference in systolic BP exceeded 10 mmHg. The mean of the two closest recordings were noted as the result. An orthostatic BP measurement was performed ten minutes preHD and postHD. Orthostatic hypotension was defined as a fall in systolic BP > 20 mmHg or a fall in diastolic BP > 10 mmHg within 3 minutes of standing according to guidelines[ 23 ]. Intradialytic hemodynamic measurements Cardiac output (CO) was obtained five times during dialysis at 10, 70, 130, 190 and 230 min using a previously validated ultrasound dilution technique (Transonic HD03 Monitor, Flow-QC tubing sets, and clip-on flow/dilution sensor from Transonic Systems Inc., Ithaca, NY,USA)[ 24 – 27 ]. Methodology has been described in detail previously[ 21 ] and is also given in the Supplementary material. Statistical analyses Sample size calculation and statistical analyses are given in the Supplementary material. Results Fourteen patients completed both interventions as shown in Figure 1. Baseline characteristics are shown in Table 1. No changes in medications affecting BP were made during the study. There was no difference between change in relative blood volume, change in weight and cumulative ultrafiltration volume when comparing interventions, see Table 2. Fluid status before dialysis was similar before each intervention according to bioimpedance measurement and mean between intervention differences preHD were not significantly different (Total body water: -1(-3.3;1.2) liters; Extracellular volume: -0.6(-1.6;0.3) liters; Intracellular volume: -0.4(-1.9;1.0) liters). Temperature Arterial line temperature as a marker of body temperature remained stable with LDT (mean within treatment change 0.0(-0.2;0.1)°C) but increased with HDT (mean within treatment change 0.4 (0.2;0.6)°C) as shown in Table 2 and Figure 2. Change over time from start to end of HD was significantly different between LDT and HDT with mean difference -0.4(-0.6;-0.3)°C, P< 0.01. The development over time was also significantly different in mixed model analysis which yielded P <0.0001 (LDT vs. HDT). If all intradialytic measurements were averaged mean arterial line temperature was -0.5(-0.7;-0.4)°C; P <0.001 lower with LDT compared to HDT in mixed model summary statistics analysis. Blood pressure While systolic BP tended to gradually decrease during HDT, little change in systolic BP was observed during LDT (Figure 3A). BP changes prior to termination of dialysis (230 min) are given in Table 3 and changes between pre-dialysis and post-dialysis BP can be found in Table 2. Systolic BP had on average decreased by an additional 12(2;21) mmHg; P =0.02 with HDT compared to LDT at 230 minutes. When PreHD vs. PostHD change in systolic BP was compared a significant difference of 9(1;18) mmHg; P =0.03 was found between LDT and HDT. Mixed model analysis found a significant difference in the systolic BP response over time from preHD to 230 minutes ( P =0.02) and from preHD to postHD ( P =0.03) when LDT was compared with HDT. If all intradialytic BP measurements were averaged mean intradialytic systolic BP was -8(-11;-4) mmHg; P <0.001 lower with HDT compared to LDT in mixed model summary statistics analysis. The difference in the systolic BP response between interventions was largest after 130 minutes where it had decreased by an additional -10(-16;-4) mmHg; P =0.002 with HDT compared to LDT. The mean fall in systolic BP from PreHD to the lowest recorded intradialytic BP was 20.3 ± 10.5 mmHg (HDT) and 9.6 ± 8.8 mmHg (LDT) with a mean between intervention difference of 10.7 (3.2; 17.9) mmHg; P =0.007. Diastolic BP remained stable with LDT and tended to decrease during dialysis with HDT. Mixed model analysis found a significant difference in the diastolic BP response over time from preHD to 230 minutes ( P =0.04) and from preHD to postHD ( P =0.03) when comparing LDT with HDT. If all intradialytic BP measurements were averaged mean diastolic BP was -3(-5;-1) mmHg; P =0.01 lower with HDT compared to HDT in mixed model summary statistics analysis. The difference in the diastolic BP response between interventions was largest after 190 minutes where it on average had decreased by an additional 6(1;12) mmHg; P =0.02 with HDT compared to LDT. An increase in both systolic and diastolic BP after termination of HD occurred regardless of the intervention. Orthostatic blood pressure Figure 4A show preHD and postHD orthostatic BP with HDT and LDT, respectively. Frequency of orthostatic hypotension and actual changes in systolic BP are given in Supplementary material, Table A. Regardless of intervention, no patients had a fall in diastolic BP >10 mmHg without also having a fall in systolic BP>20 mmHg. There was no significant difference in the postHD frequency of orthostatic hypotension when comparing interventions (LDT 43%, HDT 54%, P =0.57). The frequency of orthostatic hypotension increased significantly from preHD to postHD after HDT (7% vs. 54%); P =0.01) but not after LDT (21% vs. 43%) P =0.23). Regardless of the intervention, there was a significantly greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between HDT and LDT. Mean between intervention difference postHD was -2(-9; 5) mmHg; P =0.52. Overall, patients responded similarly during orthostatic test postHD and change in systolic BP was not significantly correlated with ultrafiltration volume (Figures 4B-D). With HDT, the fall in diastolic BP during orthostatic test was significantly greater postHD compared to preHD and mean difference (PreHD vs. PostHD) was 5 (1-9) mmHg; P =0.02. With LDT, the fall in diastolic BP during ortostatic test was not significantly different postHD compared to preHD and mean difference (PreHD vs. PostHD) was 1 (-4; 7) mmHg; P =0.60. Heart rate and intradialytic hemodynamic parameters Heart rate tended to increase during dialysis with HDT whereas dialysis with LDT showed little change in heart rate (Figure 3B, Table 3 and Supplementary material). The intradialytic heart rate response was significantly different between preHD and 230 minutes with a mean between intervention difference of -6.6(-13.0;-0.2) beats/min; P =0.04. Intradialytic hemodynamic parameters obtained during dialysis are presented in Table 3 and Figure 5. Overall, mixed model analysis showed no significant difference between LDT and HDT regarding intradialytic CO, stroke volume (SV), total peripheral resistance (TPR) and central blood volume (CBV). Both CO and SV decreased during dialysis without any significant differences between interventions. SV tended to be higher during LDT compared with HDT as illustrated in Figure 5B and if all intradialytic SV measurements were averaged mean SV was 5(-2; 12) ml; P =0.14 higher with LDT compared to HDT in mixed model summary statistics analysis. TPR increased significantly over time regardless of intervention and tended to be higher with LDT as shown in Figure 5C but there was no significant difference between interventions (TPR DD=-0.6(-4.2;3.0) mmHg/(l/min)). If all intradialytic TPR measurements were averaged mean TPR was 1.3 (-0.1; 2.7) mmHg/(l/min); P =0.06 higher with LDT compared to HDT in mixed model summary statistics analysis. CBV tended to be higher with LDT but changes in CBV were not significantly different between interventions (CBV DD=0.1 (-0.2;0.4) liter). If all intradialytic CBV measurements were averaged mean CBV was 0.107(0.004; 0.210) liter; P =0.04 higher with LDT compared to HDT in mixed model summary statistics analysis. Plasma electrolytes and intradialytic symptoms There were no significant differences between LDT and HDT regarding changes in plasma electrolytes (Mg 2+ , Na + , K + , Ca 2+ and HCO 3 - ), see Supplementary material, Table B. Patients tended to report more intradialytic symptoms during dialysis with HDT. Logistic regression (intradialytic symptoms 0 or ³1) had odds ratio (HDT vs. LDT): 2.8(0.5-14.4); P =0.22. No patients reported they felt cold or shivered during LDT. Additional details are given in the Supplementary material. Discussion Our study tested the use of LDT (35°C) versus HDT (37°C) in single-blinded randomised cross-over design and found that arterial line temperature as a marker of body temperature remained stable on LDT but increased on HDT resulting in a 0.5°C lower temperature during LDT if all intradialytic measurements were averaged signifying a distinct body temperature difference during the two interventions. This temperature difference caused a significantly different BP-response during dialysis. During LDT BP remained stable, whereas HDT caused a larger fall in systolic BP of around 8–12 mmHg. At the same time HDT, caused a higher intradialytic heart rate which by the end of dialysis on average was seven beats/minute higher with HDT. As a novelty, our study investigated the impact of dialysate temperature on orthostatic hypotension. Regardless of the intervention, there was a greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between HDT and LDT. The hemodynamic response during HD in terms of the change in CO, SV, TPR and CBV was overall similar except for a tendency towards higher SV, TPR and CBV during LDT. During HD a decline in the circulating blood volume usually occurs, depending upon the ultrafiltration rate and the degree of refill from the interstitium and redistribution of blood between vascular compartments. A decrease in blood volume typically results in an increase in peripheral vascular resistance, caused by the constriction of resistance vessels, maintenance of cardiac output through elevated heart rate and myocardial contractility, and constriction of veins (capacitance vessels). A rise in the core body temperature during HD with ultrafiltration may give signals opposing those meant to counteract volume depletion and can cause IDH even with small declines in blood volume[ 10 ]. Cooler dialysate (< 36.5°C) is used for potential cardiovascular benefits including higher intradialytic BP and IDH prevention[ 3 ] possibly resulting in less cardiac and cerebral injury[ 4 , 6 ]. Overall, most studies of cooler dialysate have been small, short-term and not powered for hard endpoints such as cardiovascular events and mortality[ 28 ]. The recent MyTEMP study[ 29 ] tested center-wide delivery of personalized cooler dialysate on a large scale in 84 Canadian HD centers. Unlike our study, nurses set the dialysate temperature 0.5–0.9 degrees C below each patient's measured pre-dialysis body temperature but not below 35.5°C, or administered standard dialysate temperature (36.5°C). On average, MyTEMP achieved a dialysate temperature of 35.8°C and 36.4°C, respectively and reported that LDT did not reduce the risk of major cardiovascular events. Moreover, there was no significant difference in intradialytic systolic BP or the risk of IDH. The mean drop in intradialytic systolic BP in MyTEMP was 26.6 mmHg in the LDT group and 27.1 mmHg in the standard group compared to 20.3 mmHg (HDT) and 9.6 mmHg (LDT) in our study which also found a significant between intervention difference of 10.7(3.6–17.9) mmHg. The non-existing difference in the intradialytic BP response most likely explains why there was no difference in the composite outcome of cardiovascular death, or hospital admission with myocardial infarction, ischemic stroke or congestive heart failure during the 4-year trial period in MyTEMP. Patients in the cooler dialysate group in MyTEMP were more likely to report feeling uncomfortably cold than patients in the standard dialysate group. Thus, it is important to note that patients may not be willing to tolerate cool dialysate despite the favorable impact on intradialytic BP. Poor adherence to a cooler dialysate temperature could explain why the achieved dialysate temperature was higher than intended in the cool dialysate group in MyTEMP. Patients in our study were blinded in terms of the dialysate temperature. Beforehand, we anticipated that more patients would report discomfort such as feeling cold, shivering, or cramps during LDT in line with findings from previous studies[ 3 , 28 ]. Interestingly, we found a tendency towards fewer symptoms during LDT which suggests that 35°C is achievable in many patients without any significant discomfort. High risk patients, sensitive to IDH during HD, could benefit from greater cooling than that tested in MyTEMP and a previous meta-analysis based on a total of 484 patients from several small randomized controlled trials reported that cooled dialysate reduced the rate of IDH by 70%[ 3 ]. The effectiveness of cold dialysate in a real-world large scale setting in terms of IDH prevention and mortality was also investigated by Zoccali et al. who found that use of cooled dialysate ≤35.5°C prevented IDH, yet had no effect on overall mortality based on a cohort of 8071 patients on average followed for 13.6 months[ 30 ]. The debate is ongoing, but it seems that more and more nephrologists favor a dialysate temperature below 37°C. In our view, a personalized dialysate temperature aiming for the avoidance of warming could be sufficient to achieve optimal outcomes in most patients and, as suggested by the real-world data, those prone to IDH tend to be treated with cooler dialysate and most likely benefit from it[ 30 ]. HD patients have a higher prevalence of orthostatic hypotension than the general population, but to the best of our knowledge only one previous study investigated the impact of cooler dialysate on orthostatic BP and reported that it tended to increase standing BP postHD[ 18 ]. In our study the prevalence of orthostatic hypotension HDT/LDT was 7%/21% PreHD and increased to 53%/43% postHD. For comparison, a previous study in HD patients reported a preHD prevalence of 42%[ 15 ], and in the general population the prevalence is between 5–30%[ 31 ]. Orthostatic hypotension is associated with increased risk of falls[ 32 ] and is also associated with increased mortality in HD patients[ 15 , 16 ]. Unexpectedly, orthostatic hypotension postHD was not affected by cooler dialysate despite the higher intradialytic BP. Beforehand, we anticipated that LDT would cause stronger vasoconstriction, which would help reduce the risk of postHD orthostatic hypotension due to electrolyte changes and volume depletion. Ultrafiltration volume was similar during both interventions, and it was not significantly correlated with systolic orthostatic BP response postHD. Antihypertensive medication usually affects orthostatic BP but was not changed between interventions and is therefore unlikely to have influenced the orthostatic response. Plasma electrolytes were also similar. In conclusion, our findings on orthostatic BP suggest that the effect of LDT disappears shortly after HD. We speculate that a rise in body temperature after dialysis may cause vasodilation resulting in a similar orthostatic BP response as after HDT. Strengths and limitations Our study performed a detailed hemodynamic assessment of the effects induced by low (35°C) and high (standard) dialysate temperature (37°C) which, due to the sheer number of measurements, is difficult to perform in a large group of patients. To justify a low number of patients we used a cross-over design which lowers random variation. The ultrasound dilution method we used for intradialytic CO is accurate and superior to other commonly used methods [ 25 , 26 , 33 , 34 ] but requires an AV-fistula. We did not measure body or room temperature during interventions. Continuous monitoring of body temperature could have improved our study design but would have required repeated rectal thermometry or use of a bladder catheter with a temperature probe. Both are invasive in nature and most likely would have jeopardized patient recruitment. Our study was limited by the fact that only two dialysis sessions were compared. Long-term effects of changes in dialysate temperature could be different than the short-term effects described in the present study. External validity was impaired to some extent by our inclusion and exclusion criteria and the low number of patients but in our view still representative of the general chronic HD population. Dialysis vintage, dialysate composition (low vs. high calcium/bicarbonate), BP-medication and comorbidities such as heart disease and diabetes could also be important factors affecting the intradialytic hemodynamic response, but our small sample size does not allow for any stratified analysis in terms of these factors/subgroups. Conclusion Selecting the same dialysate temperature for all patients seems inappropriate and should be individualized aiming to keep the body temperature constant and thereby avoid warming. Some patients, particularly those who are prone to intradialytic hypotension, could benefit from greater cooling down to 35°C although patient discomfort must always be considered when lowering dialysate temperature below 36.5°C. In our study we investigated the effect of dialysate temperature of 35°C and demonstrated a clear effect in terms of higher intradialytic BP. Whether this translates into a lower frequency of cardiovascular events and improved survival remains to be clarified. Abbreviations AV-fistula BP CO CBV HD HDT HR IDH LDT SD SV Arteriovenous fistula Blood pressure Cardiac output Central blood volume Hemodialysis High dialysate temperature Heart rate Intradialytic hypotension Low dialysate temperature Standard deviation Stroke volume Declarations Ethics approval and consent to participate The study was conducted in accordance with good clinical practice and the ethical standards described in the Helsinki Declaration. Written informed consent was obtained from all participants prior to inclusion. The Central Denmark Region Committees on Biomedical Research Ethics approved the study (1-10-72-215-21). Consent for publication Not applicable Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Competing interests CDP has received consultancy fees from Astellas and Astra Zeneca (unrelated to this publication). CDP has also received an institutional research grant from Vifor Pharma (unrelated to this publica- tion). CDP received payment from Boehringer Ingelheim for travel and congress fee for the ERA 2023 Conference in Milan, Italy. JDJ has received consultancy fees from Glaxo-Smith-Kline (GSK) and from Pharmacosmos (unrelated to this publication). Funding The study was supported by funding from Department of Renal Medicine and Nyreforeningens Forskningsfond. Authors’ contributions IEHJ: Study design, analysis, data collection, interpretation of data and writing of first manuscript draft. JSKJ: Study design, analysis, data collection, interpretation of data and revision of manuscript. NHB: Study design, analysis, interpretation of data, and revision of manuscript JDJ: Study design, analysis, interpretation of data, and revision of manuscript CDP: Study design, analysis, interpretation of data, and revision of manuscript All authors approved the final manuscript. Acknowledgements The dialysis nurses at Aarhus University Hospital and Randers Regional Hospital are thanked for their assistance and great interest in the study. References Pergola PE, Habiba NM, Johnson JM: Body temperature regulation during hemodialysis in long-term patients: is it time to change dialysate temperature prescription? Am J Kidney Dis 2004, 44 (1):155-165. 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Journal of Cardiothoracic and Vascular Anesthesia 2009, 23 (6):835-840. Moser M, Kenner T: Blood flow and blood volume determinations in aorta and in coronary circulation by density dilution . Basic Research in Cardiology 1988, 83 (6):577-589. Tsujimoto Y, Tsujimoto H, Nakata Y, Kataoka Y, Kimachi M, Shimizu S, Ikenoue T, Fukuma S, Yamamoto Y, Fukuhara S: Dialysate temperature reduction for intradialytic hypotension for people with chronic kidney disease requiring haemodialysis . Cochrane Database Syst Rev 2019, 7 (7):CD012598. My Twc: Personalised cooler dialysate for patients receiving maintenance haemodialysis (MyTEMP): a pragmatic, cluster-randomised trial . Lancet 2022, 400 (10364):1693-1703. Zoccali C, Tripepi G, Neri L, Savoia M, Baro' Salvador ME, Ponce P, Hymes J, Maddux F, Mallamaci F, Stuard S: Effectiveness of Cold Hemodialysis (HD) for the Prevention of HD Hypotension and Mortality in the General HD Population . Nephrol Dial Transplant 2023. Low PA: Prevalence of orthostatic hypotension . Clin Auton Res 2008, 18 Suppl 1 :8-13. Mol A, Bui Hoang PTS, Sharmin S, Reijnierse EM, van Wezel RJA, Meskers CGM, Maier AB: Orthostatic Hypotension and Falls in Older Adults: A Systematic Review and Meta-analysis . J Am Med Dir Assoc 2019, 20 (5):589-597 e585. Cordtz J, Ladefoged SD: Pulse contour-derived cardiac output in hemodialysis patients . Hemodialysis International 2010, 14 (1):78-83. Nikiforov YV, Kisluchine VV, Chaus NI: Validation of a new method to measure cardiac output during extracorporeal detoxification . Asaio Journal 1996, 42 (5):M903-M905. Tables Table 1 Baseline characteristics n 14 Age (years) 65 ± 18 (range 21-85) Sex (Females/males) 3/11 Body mass index (kg/m 2 ) 28.0 ± 5.2 Dialysis vintage (months) 39 ± 37 24-hour urine production (ml) a 819 ± 402 Estimated dry weight (kg) 86 ± 17 Ultrafiltration volume (ml) b 2586 ± 960 Smokers (active / previous / never) 3 / 6 / 5 Co-morbidity Diabetes Ischemic heart disease Heart failure Valvular heart disease Peripheral vascular disease Stroke 4 4 5 4 1 0 Antihypertensive medication Angiotensin converting enzyme inhibitor Angiotensin II receptor blocker Alpha receptor blocker Loop diuretic Calcium receptor blocker Beta receptor blocker Alpha- and beta receptor blocker Nitrates 2 4 1 8 2 4 4 3 Usual dialysis treatment Hemodiafiltration / hemodialysis Dialysis frequency (3 / 4 sessions per week) Session duration (3.0 / 3.5 / 4.0 / 4.5 hours) Dialysis blood flow (ml/min) Dialysate Na + (mM) Dialysate HCO3 - (30 / 34 / 36 / 38 mM) Dialysate Ca 2+ (1.25 / 1.75 mM) Dialysis filter (FX100 / FX1000 / other) 12 / 2 9 / 5 1 / 5 / 6 / 2 356 ± 21 137 ± 2 1 / 5 / 6 / 2 13 / 1 1 / 12 / 1 Clinical biochemistry with reference range (pre-dialysis) Parathyroid hormone (pmol/l, 2.0-8.5) Phosphate (mmol/l, 0.71-1.23) Potassium (mmol/l, 3.5-4.6) Albumin (g/l, 34-45) C-reactive protein (mg/l, < 8.0) Hemoglobin (mmol/l, 7.3-10.5) Leukocytes (cells/l, 3.5-10 x 10 9 ) 55.8 ± 42.7 1.93 ± 0.61 4.9 ± 0.7 34.07 ± 3.45 10 ± 12 7.6 ± 0.6 6.7 ± 1.6 Data are presented as mean ± SD for continuous variables and as numbers for categorical variables. a) for 10 patients with residual renal function (24-hour urine production > 300 ml). b) at the last dialysis session before enrolment. Table 2 Comparison of pre HD vs. post HD LDT (Pre HD) Mean ± SD D LDT (HD post -HD pre ) Mean (95% CI) HDT (Pre HD) Mean ± SD D HDT (HD post -HD pre ) Mean (95% CI) DD ( D LDT vs. D HDT) Mean (95% CI) Blood pressure Systolic blood pressure (mmHg) 143 ± 22 8 (-1;17) 146 ± 23 -1 (-10;8) 9 (1;18)* Diastolic blood pressure (mmHg) 74 ± 11 2 (-5;8) 75 ± 8 2 (-1;4) 0 (-5;6) Heart rate (beats/min) 68 ± 10 0 (-7;7) 69 ± 11 5 (-1;12) -5.2 (-10.6;-0.02) * Dialysis related parameters Arterial line temperature (°C) 36.3 ± 0.4 -0.04 (-0.2;0.1) 36.5 ± 0.4 0.4 (0.2;0.6)** -0.4 (-0.6;-0.3)** Relative blood volume change (%) NA 90.7 (87.7;93.7) NA 91.8 (88.7;94.9) -1.1 (-3.2;0.9) Weight (kg) 92.6 ± 16.0 -1.7 (-2.3;-1.1) ** 86.0 ± 16.4 -1.8 (-2.4;-1.1) ** 0.1 (-0.8;1.1) Ultrafiltration volume (ml) NA 2581 (2250;2911) NA 2530 (1983;3077) 51 (-340;441) Pre HD measurements were performed approximately 20 minutes before start of HD with post-HD measurements occurring approximately 10 minutes after ending dialysis. Results are presented as mean ± SD or mean with 95% confidence interval (95% CI). Intra- and intertreatment comparisons were performed with a paired Student’s t-test (see Statistics section). NA: Not applicable HD hemodialysis, LDT low dialysate temperature, HDT high dialysate temperature * P < 0.05; ** P <0.01 Table 3 Comparison of preHD vs. last intradialytic measurement (min 230) LDT (Pre HD) Mean ± SD D LDT (HD 230 -HD PRE ) Mean (95% CI) HDT (Pre HD) Mean ± SD D HDT HD 230 -HD PRE ) Mean (95% CI) DD ( D LDT versus D HDT) Mean (95% CI) Blood pressure Systolic blood pressure (mmHg) 143 ± 22 2 (-7;11) 146 ± 23 -10 (-19;-1) * 12 (2;21.) * Diastolic blood pressure (mmHg) 74 ± 11 0 (-6;6) 75 ± 8 0 (-4;3) 0 (-5;6) Heart rate (beats/min) 68 ± 10 0 (-6;6) 69 ± 11 6 (-2;15) -6.6 (-13.0;-0.2) * Intradialytic hemodynamic parameters (10-230 min) Mean arterial blood pressure (mmHg) 98 ± 11 0 (-6;6) 96 ± 13 -1 (-6;4) 1 (-6;8) Cardiac output (l/min) q 6.1 ± 1.5 -1.0 (-1.6;-0.4) ** 6.0 ± 1.4 -1.0 (-1.7;-0.2) * 0.1 (-0.6;0.9) Stroke volume (ml) q 96 ± 26 -18 (-30;-5) ** 92 ± 29 -22 (-41;-2) * 6 (-6;17) Heart rate (beats/min) q 65 ± 11 3 (-3;9) 66 ± 12 9 (1;18) * -6 (-12;-0) * Total peripheral resistance (mmHg/(l/min)) q 17.1 ± 4.1 3.1 (0.9;5.3) * 16.5 ± 3.1 3.1 (0.4;5.9) * -0.6 (-4.2;3.0) Central blood volume (l) q 1.4 ± 0.4 -0.2 (-0.2;-0.1) ** 1.4 ± 0.4 -0.3 (-0.5;0.0) 0.1 (-0.2;0.4) Pre HD measurements were performed approximately 20 minutes before start of HD. Results are presented as mean ± SD or mean with 95% confidence interval (95% CI)). Intra- and intertreatment comparisons were performed with a paired Student’s t-test (see Statistics section). HD hemodialysis, LDT low dialysate temperature, HDT high dialysate temperature q For intradialytic hemodynamic parameters number of participant (n) varies (HDT (min 10) n=13, DHDT and DD (DLDT-DHDT) n=12) do to failed Transonic measurements. * P < 0.05;** P <0.01 Additional Declarations Competing interest reported. CDP has received consultancy fees from Astellas and Astra Zeneca (unrelated to this publication). CDP has also received an institutional research grant from Vifor Pharma (unrelated to this publica- tion). CDP received payment from Boehringer Ingelheim for travel and congress fee for the ERA 2023 Conference in Milan, Italy. JDJ has received consultancy fees from Glaxo-Smith-Kline (GSK) and from Pharmacosmos (unrelated to this publication). 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7251357","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":501024097,"identity":"d08ff425-3871-476b-981a-0cad89ed8df7","order_by":0,"name":"Ina Ejsing Hunnerup Jørgensen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAmklEQVRIiWNgGAWjYBACNiA2YGCwAbGNSdKSRoIWKDhMghY+6eYHBR/3nM/XbWDebECcw2SOGRjOeHbbctsBtuIE4rRIJBgY8xy4bWB2gMf4AJFa0j8AtZwjSUsOyJYDYC3EOiynwHDGgWQDs8NsxcR5X35G+jaDDwfsDMyON2+WIEoLyCKI4czEqgepfUCC4lEwCkbBKBiJAAC20Smi4tpaKQAAAABJRU5ErkJggg==","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ina","middleName":"Ejsing Hunnerup","lastName":"Jørgensen","suffix":""},{"id":501024098,"identity":"d05d865f-7703-40ac-83f9-ed831e82879b","order_by":1,"name":"Jonas Schandorph Kaalund Jensen","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jonas","middleName":"Schandorph Kaalund","lastName":"Jensen","suffix":""},{"id":501024099,"identity":"5dd1afce-7e2d-49f9-b0f4-574031a550b0","order_by":2,"name":"Niels Henrik Buus","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Niels","middleName":"Henrik","lastName":"Buus","suffix":""},{"id":501024100,"identity":"26f69cb8-1f92-4738-a28d-8498bcecb88e","order_by":3,"name":"Jens Dam Jensen","email":"","orcid":"","institution":"Aarhus University","correspondingAuthor":false,"prefix":"","firstName":"Jens","middleName":"Dam","lastName":"Jensen","suffix":""},{"id":501024101,"identity":"0afdd521-5da4-4c11-b990-0b389a76a963","order_by":4,"name":"Christian Daugaard Peters","email":"","orcid":"","institution":"Aarhus University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"Daugaard","lastName":"Peters","suffix":""}],"badges":[],"createdAt":"2025-07-30 09:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7251357/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7251357/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89558809,"identity":"69aa6b88-345a-44e7-a942-c0cefeeeeec5","added_by":"auto","created_at":"2025-08-21 09:58:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":110538,"visible":true,"origin":"","legend":"\u003cp\u003eA CONSORT flow chart showing the recruitment and dropout of participants throughout the study.\u003c/p\u003e\n\u003cp\u003eLDT low dialysate temperature, HDT high dialysate temperature.\u003c/p\u003e","description":"","filename":"Figure1Flowdiagram.png","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/3d6320385dc79bc7cdb990b8.png"},{"id":89559241,"identity":"ac9d857c-4f77-4e11-9777-1450dc39543e","added_by":"auto","created_at":"2025-08-21 10:06:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":151469,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eArterial line temperature changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eArterial line temperature during low (LDT) and high (HDT) dialysate temperature hemodialysis sessions. LDT low dialysate temperature, HDT high dialysate temperature.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/8e00bb5ec177de36c5d28ba3.png"},{"id":89558811,"identity":"e635412b-25d8-415d-9b64-a7b9af38090f","added_by":"auto","created_at":"2025-08-21 09:58:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":202522,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePrimary hemodynamic changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e3A) Systolic and diastolic blood pressure during low (LDT) and high (HDT) dialysate temperature hemodialysis sessions, 3B) Heart rate during LDT and HDT hemodialysis sessions.\u003c/p\u003e\n\u003cp\u003e* Indicates significant between intervention differences in mixed model analysis.\u003c/p\u003e\n\u003cp\u003eVertical dotted lines represent 10 and 230 min of dialysis.\u003c/p\u003e","description":"","filename":"Figure3AB.png","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/41aaced0958039376532f7ff.png"},{"id":89558814,"identity":"2b1d4121-f05a-455b-b6ba-9fc1125ae71e","added_by":"auto","created_at":"2025-08-21 09:58:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":410997,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOrthostatic blood pressure response\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e4A) PreHD and postHD orthostatic BP with LDT and HDT. Dashed lines indicate individual patients.\u003c/p\u003e\n\u003cp\u003e4B) Post HD change in systolic BP during orthostatic BP test with patients sorted according to the change in systolic BP after LDT and the corresponding value after HDT.\u003c/p\u003e\n\u003cp\u003e4C) Post HD change in systolic BP during orthostatic BP test with LDT response plotted against HDT response. The dashed line shows the linear correlation (n=13) which yielded β=0.85(0.40-1.30); \u003cem\u003eP\u003c/em\u003e=0.002 and r=0.78.\u003c/p\u003e\n\u003cp\u003e4D) Post HD change in systolic BP with LDT and HDT plotted against the ultrafiltration volume adjusted for body weight.\u003c/p\u003e\n\u003cp\u003eLDT low dialysate temperature, HDT high dialysate temperature.\u003c/p\u003e","description":"","filename":"Figure4ad.png","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/6f9ce2c3598f1618a7df1fac.png"},{"id":89558815,"identity":"02a35fc7-3aef-4595-b542-8a5385f37b7d","added_by":"auto","created_at":"2025-08-21 09:58:31","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":267502,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDetailed hemodynamic changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFour plots comparing the changes in cardiac output (5A), stroke volume (5B), total peripheral resistance (5C) and central blood volume (5D) during low and high dialysate temperature hemodialysis sessions.\u003c/p\u003e\n\u003cp\u003eVertical dotted lines represent 10 and 230 min of dialysis.\u003c/p\u003e\n\u003cp\u003eCBV, central blood volume; CO, cardiac output; HD, hemodialysis; SV, stroke volume; TPR, total peripheral vascular resistance.\u003c/p\u003e","description":"","filename":"Figure5AD.png","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/3ec535da5587bcfd8938edfa.png"},{"id":89561037,"identity":"ca8c197c-9328-4d26-99c0-1bc7cfb50466","added_by":"auto","created_at":"2025-08-21 10:22:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3289559,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/9e100989-2b35-4224-96d0-33da789172a2.pdf"},{"id":89559240,"identity":"81c4260e-f2a4-40aa-bd0b-2e14d5bec9b5","added_by":"auto","created_at":"2025-08-21 10:06:31","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":24976,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7251357/v1/66b3c1b514acbc7d4a5c32ac.docx"}],"financialInterests":"Competing interest reported. CDP has received consultancy fees from Astellas and Astra Zeneca (unrelated to this publication). CDP has also received an institutional research grant from Vifor Pharma (unrelated to this publica- tion). CDP received payment from Boehringer Ingelheim for travel and congress fee for the ERA 2023 Conference in Milan, Italy. JDJ has received consultancy fees from Glaxo-Smith-Kline (GSK) and from Pharmacosmos (unrelated to this publication).","formattedTitle":"Hemodynamic effects of low versus high dialysate temperature in hemodialysis patients: a single-blinded, randomised, cross-over study","fulltext":[{"header":"Background","content":"\u003cp\u003eThe optimal hemodialysis (HD) dialysate temperature is not known. HD is typically performed by use of a standard dialysate temperature of 36.5\u0026deg;C or 37.0\u0026deg;C for all patients, although the reason for this choice is not entirely clear[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Cooler dialysate (\u0026lt;\u0026thinsp;36.5\u0026deg;) could have potential cardiovascular benefits including higher intradialytic blood pressure (BP)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and less cardiac[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and cerebral injury[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. With standard HD dialysate temperatures (\u0026ge;37\u0026deg;C), core temperature increases despite net energy loss via the extracorporeal system[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It may be partly due to reduced heat loss from the skin resulting from vasoconstriction in response to blood volume reduction, but the pathophysiology is not fully clarified[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Low dialysate temperature (LDT) typically referred to as cooling of the dialysate or isothermic dialysis with temperature-controlled feedback can counteract the increase in body temperature. Studies have shown that use of LDT (in most studies 35\u0026deg;C) was associated with improved reactivity of peripheral resistance and capacitance vessels[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], increased myocardial contractility[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], reduced BP decline and lower risk of intradialytic hypotension (IDH) compared with a high dialysate temperature (HDT) of 37\u0026ndash;37.5\u0026deg;C[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, LDT could also induce a larger reduction in blood volume because of reduced refill from the interstitium due to peripheral vasoconstriction[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and cause shivering as an unpleasant side-effect[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Orthostatic hypotension is highly prevalent in HD patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and linked with an increased risk of falls and death[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], in line with findings in the general population[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Despite the obvious clinical relevance, only one previous study examined the effect of LDT on orthostatic BP and reported higher standing BP after LDT[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The aim of this study was to perform a detailed comparison of HD treatments with HDT and LDT in terms of BP, intradialytic hemodynamic parameters, and orthostatic BP response. We hypothesized that LDT of 35\u0026deg;C versus HDT of 37\u0026deg;C (standard) could result in higher BP, more stable intradialytic hemodynamics, and decreased frequency of orthostatic hypotension.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cem\u003eStudy design\u003c/em\u003e\u003c/p\u003e\u003cp\u003eThe study was a single-blinded, randomised, cross-over study. Each participant attended two dialysis sessions: one with LDT of 35\u0026deg;C and one with HDT of 37\u0026deg;C. All other parameters including dialysate composition and dialysis membrane were kept unchanged. The sessions were separated with a one-week washout period with participants attending their usual HD treatment on the other weekdays. A Fresenius 5008 (Fresenius Medical Care, Bad Homburg, Germany) dialysis machine with a built-in monitor for arterial blood line temperature (BTM) reflecting central body temperature was used in all sessions. The order of the two interventions was performed by a built-in randomization module in REDCap (Research Electronic Data Capture (hosted at Clinical Trial Unit, Department of Clinical Medicine, Aarhus University[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The study was registered at ClinicalTrials.gov where the full study protocol is available (NCT05052151). Blood sampling and bioimpedance methodology has previously been published[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] but is also described in the Supplementary material.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStudy population\u003c/em\u003e\u003c/p\u003e\u003cp\u003eHD patients were recruited from Aarhus University Hospital and Randers Regional Hospital from August-December 2021. Inclusion and exclusion criteria are given in the Supplementary material.\u003c/p\u003e\u003cp\u003e\u003cem\u003eBlood pressure, heart rate and orthostatic BP measurements\u003c/em\u003e\u003c/p\u003e\u003cp\u003eA validated BP device (Microlife BP B2 Basic BP monitor, AG Swiss Corporation, Switzerland)[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] with a fitting cuff placed on the non-AV-fistula arm was used for all measurements. Supine BP and heart rate were measured approximately 10 min before (preHD) dialysis, 5 times during (10, 70,130, 190 and 230 min) dialysis and 10 min after dialysis (postHD). Prior to measurements each participant rested for 5 minutes, whereupon two recording were made. Additional measurements were made if the difference in systolic BP exceeded 10 mmHg. The mean of the two closest recordings were noted as the result. An orthostatic BP measurement was performed ten minutes preHD and postHD. Orthostatic hypotension was defined as a fall in systolic BP\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg or a fall in diastolic BP\u0026thinsp;\u0026gt;\u0026thinsp;10 mmHg within 3 minutes of standing according to guidelines[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eIntradialytic hemodynamic measurements\u003c/em\u003e\u003c/p\u003e\u003cp\u003eCardiac output (CO) was obtained five times during dialysis at 10, 70, 130, 190 and 230 min using a previously validated ultrasound dilution technique (Transonic HD03 Monitor, Flow-QC tubing sets, and clip-on flow/dilution sensor from Transonic Systems Inc., Ithaca, NY,USA)[\u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Methodology has been described in detail previously[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and is also given in the Supplementary material.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStatistical analyses\u003c/em\u003e\u003c/p\u003e\u003cp\u003eSample size calculation and statistical analyses are given in the Supplementary material.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFourteen patients completed both interventions as shown in Figure 1. Baseline characteristics are shown in Table 1. No changes in medications affecting BP were made during the study. There was no difference between change in relative blood volume, change in weight and cumulative ultrafiltration volume when comparing interventions, see Table 2. Fluid status before dialysis was similar before each intervention according to bioimpedance measurement and mean between intervention differences preHD were not significantly different (Total body water: -1(-3.3;1.2) liters; Extracellular volume: -0.6(-1.6;0.3) liters; Intracellular volume: -0.4(-1.9;1.0) liters).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTemperature\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eArterial line temperature as a marker of body temperature remained stable with LDT (mean within treatment change 0.0(-0.2;0.1)\u0026deg;C) but increased with HDT (mean within treatment change 0.4 (0.2;0.6)\u0026deg;C) as shown in Table 2 and Figure 2. Change over time from start to end of HD was significantly different between LDT and HDT with mean difference -0.4(-0.6;-0.3)\u0026deg;C, \u003cem\u003eP\u0026lt;\u003c/em\u003e0.01. The development over time was also significantly different in mixed model analysis which yielded \u003cem\u003eP\u003c/em\u003e\u0026lt;0.0001 (LDT vs. HDT). If all intradialytic measurements were averaged mean arterial line temperature was -0.5(-0.7;-0.4)\u0026deg;C; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001 lower with LDT compared to HDT in mixed model summary statistics analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBlood pressure\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWhile systolic BP tended to gradually decrease during HDT, little change in systolic BP was observed during LDT (Figure 3A). BP changes prior to termination of dialysis (230 min) are given in Table 3 and changes between pre-dialysis and post-dialysis BP can be found in Table 2. Systolic BP had on average decreased by an additional 12(2;21) mmHg; \u003cem\u003eP\u003c/em\u003e=0.02 with HDT compared to LDT at 230 minutes. When PreHD vs. PostHD change in systolic BP was compared a significant difference of 9(1;18) mmHg; \u003cem\u003eP\u003c/em\u003e=0.03 was found between LDT and HDT. Mixed model analysis found a significant difference in the systolic BP response over time from preHD to 230 minutes (\u003cem\u003eP\u003c/em\u003e=0.02) and from preHD to postHD (\u003cem\u003eP\u003c/em\u003e=0.03) when LDT was compared with HDT. If all intradialytic BP measurements were averaged mean intradialytic systolic BP was -8(-11;-4) mmHg; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001 lower with HDT compared to LDT in mixed model summary statistics analysis. The difference in the systolic BP response between interventions was largest after 130 minutes where it had decreased by an additional -10(-16;-4) mmHg; \u003cem\u003eP\u003c/em\u003e=0.002 with HDT compared to LDT. The mean fall in systolic BP from PreHD to the lowest recorded intradialytic BP was 20.3\u0026nbsp;\u0026plusmn;\u0026nbsp;10.5 mmHg (HDT) and 9.6\u0026nbsp;\u0026plusmn;\u0026nbsp;8.8 mmHg (LDT) with a mean between intervention difference of 10.7 (3.2; 17.9) mmHg; \u003cem\u003eP\u003c/em\u003e=0.007.\u003c/p\u003e\n\u003cp\u003eDiastolic BP remained stable with LDT and tended to decrease during dialysis with HDT. Mixed model analysis found a significant difference in the diastolic BP response over time from preHD to 230 minutes (\u003cem\u003eP\u003c/em\u003e=0.04) and from preHD to postHD (\u003cem\u003eP\u003c/em\u003e=0.03) when comparing LDT with HDT.\u003c/p\u003e\n\u003cp\u003eIf all intradialytic BP measurements were averaged mean diastolic BP was -3(-5;-1) mmHg; \u003cem\u003eP\u003c/em\u003e=0.01 lower with HDT compared to HDT in mixed model summary statistics analysis.\u003c/p\u003e\n\u003cp\u003eThe difference in the diastolic BP response between interventions was largest after 190 minutes where it on average had decreased by an additional 6(1;12) mmHg; \u003cem\u003eP\u003c/em\u003e=0.02 with HDT compared to LDT. An increase in both systolic and diastolic BP after termination of HD occurred regardless of the intervention.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOrthostatic blood pressure\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFigure 4A show preHD and postHD orthostatic BP with HDT and LDT, respectively. Frequency of orthostatic hypotension and actual changes in systolic BP are given in Supplementary material, Table A. Regardless of intervention, no patients had a fall in diastolic BP \u0026gt;10 mmHg without also having a fall in systolic BP\u0026gt;20 mmHg. There was no significant difference in the postHD frequency of orthostatic hypotension when comparing interventions (LDT 43%, HDT 54%, \u003cem\u003eP\u003c/em\u003e=0.57). The frequency of orthostatic hypotension increased significantly from preHD to postHD after HDT (7% vs. 54%); \u003cem\u003eP\u003c/em\u003e=0.01) but not after LDT (21% vs. 43%)\u003cem\u003e\u0026nbsp;P\u003c/em\u003e=0.23). Regardless of the intervention, there was a significantly greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between HDT and LDT. Mean between intervention difference postHD was -2(-9; 5) mmHg; \u003cem\u003eP\u003c/em\u003e=0.52. Overall, patients responded similarly during orthostatic test postHD and change in systolic BP was not significantly correlated with ultrafiltration volume (Figures 4B-D).\u003c/p\u003e\n\u003cp\u003eWith HDT, the fall in diastolic BP during orthostatic test was significantly greater postHD compared to preHD and mean difference (PreHD vs. PostHD) was 5 (1-9) mmHg; \u003cem\u003eP\u003c/em\u003e=0.02. With LDT, the fall in diastolic BP during ortostatic test was not significantly different postHD compared to preHD and mean difference (PreHD vs. PostHD) was 1 (-4; 7) mmHg; \u003cem\u003eP\u003c/em\u003e=0.60.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHeart rate and intradialytic hemodynamic parameters\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHeart rate tended to increase during dialysis with HDT whereas dialysis with LDT showed little change in heart rate (Figure 3B, Table 3 and Supplementary material). The intradialytic heart rate response was significantly different between preHD and 230 minutes with a mean between intervention difference of -6.6(-13.0;-0.2) beats/min; \u003cem\u003eP\u003c/em\u003e=0.04. Intradialytic hemodynamic parameters obtained during dialysis are presented in Table 3 and Figure 5. Overall, mixed model analysis showed no significant difference between LDT and HDT regarding intradialytic CO, stroke volume (SV), total peripheral resistance (TPR) and central blood volume (CBV). Both CO and SV decreased during dialysis without any significant differences between interventions. SV tended to be higher during LDT compared with HDT as illustrated in Figure 5B and if all intradialytic SV measurements were averaged mean SV was 5(-2; 12) ml; \u003cem\u003eP\u003c/em\u003e=0.14 higher with LDT compared to HDT in mixed model summary statistics analysis. TPR increased significantly over time regardless of intervention and tended to be higher with LDT as shown in Figure 5C but there was no significant difference between interventions (TPR DD=-0.6(-4.2;3.0) mmHg/(l/min)). If all intradialytic TPR measurements were averaged mean TPR was 1.3 (-0.1; 2.7) mmHg/(l/min); \u003cem\u003eP\u003c/em\u003e=0.06 higher with LDT compared to HDT in mixed model summary statistics analysis. CBV tended to be higher with LDT but changes in CBV were not significantly different between interventions (CBV DD=0.1 (-0.2;0.4) liter). If all intradialytic CBV measurements were averaged mean CBV was 0.107(0.004; 0.210) liter; \u003cem\u003eP\u003c/em\u003e=0.04 higher with LDT compared to HDT in mixed model summary statistics analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePlasma electrolytes and intradialytic symptoms\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThere were no significant differences between LDT and HDT regarding changes in plasma electrolytes (Mg\u003csup\u003e2+\u003c/sup\u003e, Na\u003csup\u003e+\u003c/sup\u003e, K\u003csup\u003e+\u003c/sup\u003e, Ca\u003csup\u003e2+\u003c/sup\u003e and HCO\u003csub\u003e3\u003c/sub\u003e\u003csup\u003e-\u003c/sup\u003e), see Supplementary material, Table B. Patients tended to report more intradialytic symptoms during dialysis with HDT. Logistic regression (intradialytic symptoms 0 or \u0026nbsp;\u0026sup3;1) had odds ratio (HDT vs. LDT): 2.8(0.5-14.4); \u003cem\u003eP\u003c/em\u003e=0.22. No patients reported they felt cold or shivered during LDT. Additional details are given in the Supplementary material.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study tested the use of LDT (35\u0026deg;C) versus HDT (37\u0026deg;C) in single-blinded randomised cross-over design and found that arterial line temperature as a marker of body temperature remained stable on LDT but increased on HDT resulting in a 0.5\u0026deg;C lower temperature during LDT if all intradialytic measurements were averaged signifying a distinct body temperature difference during the two interventions. This temperature difference caused a significantly different BP-response during dialysis. During LDT BP remained stable, whereas HDT caused a larger fall in systolic BP of around 8\u0026ndash;12 mmHg. At the same time HDT, caused a higher intradialytic heart rate which by the end of dialysis on average was seven beats/minute higher with HDT. As a novelty, our study investigated the impact of dialysate temperature on orthostatic hypotension. Regardless of the intervention, there was a greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between HDT and LDT. The hemodynamic response during HD in terms of the change in CO, SV, TPR and CBV was overall similar except for a tendency towards higher SV, TPR and CBV during LDT.\u003c/p\u003e\u003cp\u003eDuring HD a decline in the circulating blood volume usually occurs, depending upon the ultrafiltration rate and the degree of refill from the interstitium and redistribution of blood between vascular compartments. A decrease in blood volume typically results in an increase in peripheral vascular resistance, caused by the constriction of resistance vessels, maintenance of cardiac output through elevated heart rate and myocardial contractility, and constriction of veins (capacitance vessels). A rise in the core body temperature during HD with ultrafiltration may give signals opposing those meant to counteract volume depletion and can cause IDH even with small declines in blood volume[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Cooler dialysate (\u0026lt;\u0026thinsp;36.5\u0026deg;C) is used for potential cardiovascular benefits including higher intradialytic BP and IDH prevention[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] possibly resulting in less cardiac and cerebral injury[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Overall, most studies of cooler dialysate have been small, short-term and not powered for hard endpoints such as cardiovascular events and mortality[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The recent MyTEMP study[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] tested center-wide delivery of personalized cooler dialysate on a large scale in 84 Canadian HD centers. Unlike our study, nurses set the dialysate temperature 0.5\u0026ndash;0.9 degrees C below each patient's measured pre-dialysis body temperature but not below 35.5\u0026deg;C, or administered standard dialysate temperature (36.5\u0026deg;C). On average, MyTEMP achieved a dialysate temperature of 35.8\u0026deg;C and 36.4\u0026deg;C, respectively and reported that LDT did not reduce the risk of major cardiovascular events. Moreover, there was no significant difference in intradialytic systolic BP or the risk of IDH. The mean drop in intradialytic systolic BP in MyTEMP was 26.6 mmHg in the LDT group and 27.1 mmHg in the standard group compared to 20.3 mmHg (HDT) and 9.6 mmHg (LDT) in our study which also found a significant between intervention difference of 10.7(3.6\u0026ndash;17.9) mmHg. The non-existing difference in the intradialytic BP response most likely explains why there was no difference in the composite outcome of cardiovascular death, or hospital admission with myocardial infarction, ischemic stroke or congestive heart failure during the 4-year trial period in MyTEMP. Patients in the cooler dialysate group in MyTEMP were more likely to report feeling uncomfortably cold than patients in the standard dialysate group. Thus, it is important to note that patients may not be willing to tolerate cool dialysate despite the favorable impact on intradialytic BP. Poor adherence to a cooler dialysate temperature could explain why the achieved dialysate temperature was higher than intended in the cool dialysate group in MyTEMP. Patients in our study were blinded in terms of the dialysate temperature. Beforehand, we anticipated that more patients would report discomfort such as feeling cold, shivering, or cramps during LDT in line with findings from previous studies[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Interestingly, we found a tendency towards fewer symptoms during LDT which suggests that 35\u0026deg;C is achievable in many patients without any significant discomfort. High risk patients, sensitive to IDH during HD, could benefit from greater cooling than that tested in MyTEMP and a previous meta-analysis based on a total of 484 patients from several small randomized controlled trials reported that cooled dialysate reduced the rate of IDH by 70%[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The effectiveness of cold dialysate in a real-world large scale setting in terms of IDH prevention and mortality was also investigated by Zoccali et al. who found that use of cooled dialysate \u0026le;35.5\u0026deg;C prevented IDH, yet had no effect on overall mortality based on a cohort of 8071 patients on average followed for 13.6 months[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The debate is ongoing, but it seems that more and more nephrologists favor a dialysate temperature below 37\u0026deg;C. In our view, a personalized dialysate temperature aiming for the avoidance of warming could be sufficient to achieve optimal outcomes in most patients and, as suggested by the real-world data, those prone to IDH tend to be treated with cooler dialysate and most likely benefit from it[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eHD patients have a higher prevalence of orthostatic hypotension than the general population, but to the best of our knowledge only one previous study investigated the impact of cooler dialysate on orthostatic BP and reported that it tended to increase standing BP postHD[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our study the prevalence of orthostatic hypotension HDT/LDT was 7%/21% PreHD and increased to 53%/43% postHD. For comparison, a previous study in HD patients reported a preHD prevalence of 42%[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and in the general population the prevalence is between 5\u0026ndash;30%[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Orthostatic hypotension is associated with increased risk of falls[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and is also associated with increased mortality in HD patients[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Unexpectedly, orthostatic hypotension postHD was not affected by cooler dialysate despite the higher intradialytic BP. Beforehand, we anticipated that LDT would cause stronger vasoconstriction, which would help reduce the risk of postHD orthostatic hypotension due to electrolyte changes and volume depletion. Ultrafiltration volume was similar during both interventions, and it was not significantly correlated with systolic orthostatic BP response postHD. Antihypertensive medication usually affects orthostatic BP but was not changed between interventions and is therefore unlikely to have influenced the orthostatic response. Plasma electrolytes were also similar. In conclusion, our findings on orthostatic BP suggest that the effect of LDT disappears shortly after HD. We speculate that a rise in body temperature after dialysis may cause vasodilation resulting in a similar orthostatic BP response as after HDT.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStrengths and limitations\u003c/em\u003e\u003c/p\u003e\u003cp\u003eOur study performed a detailed hemodynamic assessment of the effects induced by low (35\u0026deg;C) and high (standard) dialysate temperature (37\u0026deg;C) which, due to the sheer number of measurements, is difficult to perform in a large group of patients. To justify a low number of patients we used a cross-over design which lowers random variation. The ultrasound dilution method we used for intradialytic CO is accurate and superior to other commonly used methods [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] but requires an AV-fistula. We did not measure body or room temperature during interventions. Continuous monitoring of body temperature could have improved our study design but would have required repeated rectal thermometry or use of a bladder catheter with a temperature probe. Both are invasive in nature and most likely would have jeopardized patient recruitment. Our study was limited by the fact that only two dialysis sessions were compared. Long-term effects of changes in dialysate temperature could be different than the short-term effects described in the present study. External validity was impaired to some extent by our inclusion and exclusion criteria and the low number of patients but in our view still representative of the general chronic HD population. Dialysis vintage, dialysate composition (low vs. high calcium/bicarbonate), BP-medication and comorbidities such as heart disease and diabetes could also be important factors affecting the intradialytic hemodynamic response, but our small sample size does not allow for any stratified analysis in terms of these factors/subgroups.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSelecting the same dialysate temperature for all patients seems inappropriate and should be individualized aiming to keep the body temperature constant and thereby avoid warming.\u003c/p\u003e\u003cp\u003eSome patients, particularly those who are prone to intradialytic hypotension, could benefit from greater cooling down to 35\u0026deg;C although patient discomfort must always be considered when lowering dialysate temperature below 36.5\u0026deg;C. In our study we investigated the effect of dialysate temperature of 35\u0026deg;C and demonstrated a clear effect in terms of higher intradialytic BP. Whether this translates into a lower frequency of cardiovascular events and improved survival remains to be clarified.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 226px;\"\u003e\n \u003cp\u003eAV-fistula\u003c/p\u003e\n \u003cp\u003eBP\u003c/p\u003e\n \u003cp\u003eCO\u003c/p\u003e\n \u003cp\u003eCBV\u003c/p\u003e\n \u003cp\u003eHD\u003c/p\u003e\n \u003cp\u003eHDT\u003c/p\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003cp\u003eIDH\u003c/p\u003e\n \u003cp\u003eLDT\u003c/p\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003cp\u003eSV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 375px;\"\u003e\n \u003cp\u003eArteriovenous fistula\u003c/p\u003e\n \u003cp\u003eBlood pressure\u003c/p\u003e\n \u003cp\u003eCardiac output\u003c/p\u003e\n \u003cp\u003eCentral blood volume\u003c/p\u003e\n \u003cp\u003eHemodialysis\u003c/p\u003e\n \u003cp\u003eHigh dialysate temperature\u003c/p\u003e\n \u003cp\u003eHeart rate\u003c/p\u003e\n \u003cp\u003eIntradialytic hypotension\u003c/p\u003e\n \u003cp\u003eLow dialysate temperature\u003c/p\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003cp\u003eStroke volume\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with good clinical practice and the ethical standards described in the Helsinki Declaration. Written informed consent was obtained from all participants prior to inclusion. The Central Denmark Region Committees on Biomedical Research Ethics approved the study (1-10-72-215-21).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCDP has received consultancy fees from Astellas and Astra Zeneca (unrelated to this publication). CDP has also received an institutional research grant from Vifor Pharma (unrelated to this publica- tion). CDP received payment from Boehringer Ingelheim for travel and congress fee for the ERA 2023 Conference in Milan, Italy. JDJ has received consultancy fees from Glaxo-Smith-Kline (GSK) and from Pharmacosmos (unrelated to this publication).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was supported by funding from Department of Renal Medicine and Nyreforeningens Forskningsfond.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIEHJ: Study design, analysis, data collection, interpretation of data and writing of first manuscript draft.\u003c/p\u003e\n\u003cp\u003eJSKJ: Study design, analysis, data collection, interpretation of data and revision of manuscript.\u003c/p\u003e\n\u003cp\u003eNHB:\u0026nbsp;Study design, analysis, interpretation of data, and revision of manuscript\u003c/p\u003e\n\u003cp\u003eJDJ: Study design, analysis, interpretation of data, and revision of manuscript\u003c/p\u003e\n\u003cp\u003eCDP: Study design, analysis, interpretation of data, and revision of manuscript\u003c/p\u003e\n\u003cp\u003eAll authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dialysis nurses at Aarhus University Hospital and Randers Regional Hospital are thanked for their assistance and great interest in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePergola PE, Habiba NM, Johnson JM: \u003cstrong\u003eBody temperature regulation during hemodialysis in long-term patients: is it time to change dialysate temperature prescription?\u003c/strong\u003e \u003cem\u003eAm J Kidney Dis \u003c/em\u003e2004, \u003cstrong\u003e44\u003c/strong\u003e(1):155-165.\u003c/li\u003e\n\u003cli\u003eMaggiore Q, Pizzarelli F, Santoro A, Panzetta G, Bonforte G, Hannedouche T, Alvarez de Lara MA, Tsouras I, Loureiro A, Ponce P\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eThe effects of control of thermal balance on 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hemodialysis patients\u003c/strong\u003e. \u003cem\u003eHemodialysis International \u003c/em\u003e2010, \u003cstrong\u003e14\u003c/strong\u003e(1):78-83.\u003c/li\u003e\n\u003cli\u003eNikiforov YV, Kisluchine VV, Chaus NI: \u003cstrong\u003eValidation of a new method to measure cardiac output during extracorporeal detoxification\u003c/strong\u003e. \u003cem\u003eAsaio Journal \u003c/em\u003e1996, \u003cstrong\u003e42\u003c/strong\u003e(5):M903-M905.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1 Baseline characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e65\u0026nbsp;\u0026plusmn;\u0026nbsp;18 (range 21-85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eSex (Females/males)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e3/11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e28.0\u0026nbsp;\u0026plusmn;\u0026nbsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eDialysis vintage (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e39\u0026nbsp;\u0026plusmn;\u0026nbsp;37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003e24-hour urine production (ml)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e819\u0026nbsp;\u0026plusmn;\u0026nbsp;402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eEstimated dry weight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e86\u0026nbsp;\u0026plusmn;\u0026nbsp;17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eUltrafiltration volume (ml)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e2586\u0026nbsp;\u0026plusmn;\u0026nbsp;960\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eSmokers (active / previous / never)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e3 / 6 / 5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eCo-morbidity\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Diabetes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Ischemic heart disease\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Heart failure\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Valvular heart disease\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Peripheral vascular disease\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eAntihypertensive medication\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Angiotensin converting enzyme inhibitor\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Angiotensin II receptor blocker\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Alpha receptor blocker\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Loop diuretic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Calcium receptor blocker\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Beta receptor blocker\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Alpha- and beta receptor blocker\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Nitrates\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eUsual dialysis treatment\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Hemodiafiltration / hemodialysis\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysis frequency (3 / 4 sessions per week)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Session duration (3.0 / 3.5 / 4.0 / 4.5 hours)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysis blood flow (ml/min)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysate Na\u003csup\u003e+\u003c/sup\u003e (mM)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysate HCO3\u003csup\u003e-\u003c/sup\u003e (30 / 34 / 36 / 38 mM)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysate Ca\u003csup\u003e2+\u003c/sup\u003e (1.25 / 1.75 mM) \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Dialysis filter (FX100 / FX1000 / other)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 / 2\u003c/p\u003e\n \u003cp\u003e9 / 5\u003c/p\u003e\n \u003cp\u003e1 / 5 / 6 / 2\u003c/p\u003e\n \u003cp\u003e356\u0026nbsp;\u0026plusmn;\u0026nbsp;21\u003c/p\u003e\n \u003cp\u003e137\u0026nbsp;\u0026plusmn;\u0026nbsp;2\u003c/p\u003e\n \u003cp\u003e1 / 5 / 6 / 2\u003c/p\u003e\n \u003cp\u003e13 / 1\u003c/p\u003e\n \u003cp\u003e1 / 12 / 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 431px;\"\u003e\n \u003cp\u003eClinical biochemistry with reference range (pre-dialysis)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Parathyroid hormone (pmol/l, 2.0-8.5)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Phosphate (mmol/l, 0.71-1.23)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Potassium (mmol/l, 3.5-4.6)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Albumin (g/l, 34-45)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; C-reactive protein (mg/l, \u0026lt; 8.0)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Hemoglobin (mmol/l, 7.3-10.5)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Leukocytes (cells/l, 3.5-10 x 10\u003csup\u003e9\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 212px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e55.8\u0026nbsp;\u0026plusmn;\u0026nbsp;42.7\u003c/p\u003e\n \u003cp\u003e1.93\u0026nbsp;\u0026plusmn;\u0026nbsp;0.61\u003c/p\u003e\n \u003cp\u003e4.9\u0026nbsp;\u0026plusmn;\u0026nbsp;0.7\u003c/p\u003e\n \u003cp\u003e34.07\u0026nbsp;\u0026plusmn;\u0026nbsp;3.45\u003c/p\u003e\n \u003cp\u003e10\u0026nbsp;\u0026plusmn;\u0026nbsp;12\u003c/p\u003e\n \u003cp\u003e7.6\u0026nbsp;\u0026plusmn;\u0026nbsp;0.6\u003c/p\u003e\n \u003cp\u003e6.7\u0026nbsp;\u0026plusmn;\u0026nbsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD for continuous variables and as numbers for categorical variables.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea)\u003c/sup\u003e for 10 patients with residual renal function (24-hour urine production \u0026gt; 300 ml).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb)\u003c/sup\u003e at the last dialysis session before enrolment.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Comparison of pre HD vs. post HD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"943\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Pre HD)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026nbsp;\u0026plusmn;\u0026nbsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eLDT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(HD\u003csub\u003epost\u003c/sub\u003e-HD\u003csub\u003epre\u003c/sub\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Pre HD)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026nbsp;\u0026plusmn;\u0026nbsp;SD\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eHDT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(HD\u003csub\u003epost\u003c/sub\u003e-HD\u003csub\u003epre\u003c/sub\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDD\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eLDT vs.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eHDT)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 943px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood pressure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e143\u0026nbsp;\u0026plusmn;\u0026nbsp;22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e8 (-1;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e146\u0026nbsp;\u0026plusmn;\u0026nbsp;23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e-1 (-10;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e9 (1;18)*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eDiastolic blood pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e74\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e2 (-5;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e75\u0026nbsp;\u0026plusmn;\u0026nbsp;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2 (-1;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e0 (-5;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eHeart rate (beats/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e68\u0026nbsp;\u0026plusmn;\u0026nbsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e0 (-7;7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e69\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e5 (-1;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e-5.2 (-10.6;-0.02) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 943px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDialysis related parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eArterial line temperature (\u0026deg;C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e36.3\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e-0.04 (-0.2;0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e36.5\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.4 (0.2;0.6)**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e-0.4 (-0.6;-0.3)**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eRelative blood volume change (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e90.7 (87.7;93.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e91.8 (88.7;94.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e-1.1 (-3.2;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e92.6\u0026nbsp;\u0026plusmn;\u0026nbsp;16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e-1.7 (-2.3;-1.1) **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003e86.0\u0026nbsp;\u0026plusmn;\u0026nbsp;16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e-1.8 (-2.4;-1.1) **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e0.1 (-0.8;1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 272px;\"\u003e\n \u003cp\u003eUltrafiltration volume (ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 137px;\"\u003e\n \u003cp\u003e2581 (2250;2911)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 105px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2530 (1983;3077)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 189px;\"\u003e\n \u003cp\u003e51 (-340;441)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePre HD measurements were performed approximately 20 minutes before start of HD with post-HD measurements occurring approximately 10 minutes after ending dialysis. Results are presented as mean \u0026plusmn; SD or mean with 95% confidence interval (95% CI).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIntra- and intertreatment comparisons were performed with a paired Student\u0026rsquo;s t-test (see Statistics section).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNA: Not applicable\u003c/p\u003e\n\u003cp\u003eHD hemodialysis, LDT low dialysate temperature, HDT high dialysate temperature\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*\u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05; **\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01\u003cstrong\u003e\u003cbr\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Comparison of preHD vs. last intradialytic measurement (min 230)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"848\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Pre HD)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026nbsp;\u0026plusmn;\u0026nbsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eLDT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(HD\u003csub\u003e230\u003c/sub\u003e-HD\u003csub\u003ePRE\u003c/sub\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Pre HD)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean\u0026nbsp;\u0026plusmn;\u0026nbsp;SD\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eHDT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHD\u003csub\u003e230\u003c/sub\u003e-HD\u003csub\u003ePRE\u003c/sub\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDD\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eLDT versus\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eD\u003c/strong\u003e\u003cstrong\u003eHDT)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eMean (95% CI)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 848px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBlood pressure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e143\u0026nbsp;\u0026plusmn;\u0026nbsp;22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e2 (-7;11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e146\u0026nbsp;\u0026plusmn;\u0026nbsp;23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e-10 (-19;-1) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e12 (2;21.) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eDiastolic blood pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e74\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (-6;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e75\u0026nbsp;\u0026plusmn;\u0026nbsp;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e0 (-4;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e0 (-5;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eHeart rate (beats/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e68\u0026nbsp;\u0026plusmn;\u0026nbsp;10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (-6;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e69\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e6 (-2;15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e-6.6 (-13.0;-0.2) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 848px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntradialytic hemodynamic parameters (10-230 min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eMean arterial blood pressure (mmHg)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e98\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0 (-6;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e96\u0026nbsp;\u0026plusmn;\u0026nbsp;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e-1 (-6;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e1 (-6;8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eCardiac output (l/min)\u0026nbsp;q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e6.1\u0026nbsp;\u0026plusmn;\u0026nbsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e-1.0 (-1.6;-0.4) **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e6.0\u0026nbsp;\u0026plusmn;\u0026nbsp;1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e-1.0 (-1.7;-0.2) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e0.1 (-0.6;0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eStroke volume (ml)\u0026nbsp;q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e96\u0026nbsp;\u0026plusmn;\u0026nbsp;26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e-18 (-30;-5) **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e92\u0026nbsp;\u0026plusmn;\u0026nbsp;29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e-22 (-41;-2) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e6 (-6;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eHeart rate (beats/min) \u0026nbsp;q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e65\u0026nbsp;\u0026plusmn;\u0026nbsp;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e3 (-3;9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e66\u0026nbsp;\u0026plusmn;\u0026nbsp;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e9 (1;18) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e-6 (-12;-0) *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eTotal peripheral resistance (mmHg/(l/min))\u0026nbsp;q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e17.1\u0026nbsp;\u0026plusmn;\u0026nbsp;4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e3.1 (0.9;5.3) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e16.5\u0026nbsp;\u0026plusmn;\u0026nbsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e3.1 (0.4;5.9) *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e-0.6 (-4.2;3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 245px;\"\u003e\n \u003cp\u003eCentral blood volume (l)\u0026nbsp;q\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e1.4\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e-0.2 (-0.2;-0.1) **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1.4\u0026nbsp;\u0026plusmn;\u0026nbsp;0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 122px;\"\u003e\n \u003cp\u003e-0.3 (-0.5;0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 170px;\"\u003e\n \u003cp\u003e0.1 (-0.2;0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePre HD measurements were performed approximately 20 minutes before start of HD. Results are presented as mean \u0026plusmn; SD or mean with 95% confidence interval (95% CI)). Intra- and intertreatment comparisons were performed with a paired Student\u0026rsquo;s t-test (see Statistics section).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHD hemodialysis, LDT low dialysate temperature, HDT high dialysate temperature\u003c/p\u003e\n\u003cp\u003eq For intradialytic hemodynamic parameters number of participant (n) varies (HDT (min 10) n=13, DHDT and \u0026nbsp;DD (DLDT-DHDT) n=12) do to failed Transonic measurements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e*\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05;**\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Blood pressure, chronic renal failure, dialysis, temperature, hemodynamics","lastPublishedDoi":"10.21203/rs.3.rs-7251357/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7251357/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eCooling of the dialysate may improve intradialytic hemodynamics. This study compared low dialysate temperature (LDT) of 35\u0026deg;C with high dialysate temperature (HDT) of 37\u0026deg;C (standard) in terms of blood pressure (BP), intradialytic hemodynamics, and orthostatic BP.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eIn a single-blind, randomised, controlled, crossover study fourteen hemodialysis (HD) patients underwent a 4-h HD session with LDT (35\u0026deg;C) or HDT (37\u0026deg;C) separated by a 1- week interval. BP was monitored throughout HD. Intradialytic hemodynamics were assessed with ultrasound dilution technique (Transonic). Orthostatic BP was measured pre- and postHD.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eUltrafiltration (mean with 95% confidence interval) was similar (LDT: 2.6(2.3;2.9) vs HDT: 2.5(2.0;3.1) liters). Arterial line temperature as a marker of body temperature remained stable with LDT but increased with HDT (mean change LDT: 0.0(-0.2;0.1) vs. HDT: 0.4(0.2;0.6)\u0026deg;C) with a mean between intervention difference of -0.4(-0.6;-0.3)\u0026deg;C. BP remained relatively stable on LDT, whereas HDT caused a significantly larger fall in systolic BP. The mean (\u0026plusmn; SD) fall in intradialytic systolic BP (PreHD vs. lowest intradialytic) was 20.3 \u0026plusmn; 10.5 mmHg (HDT) and 9.6 \u0026plusmn; 8.8 mmHg (LDT) with a mean between intervention difference of 10.7(3.2; 17.9) mmHg. LDT caused a significantly lower intradialytic heart rate which by the end of dialysis (after 230 minutes) on average was \u0026minus;\u0026thinsp;6.6(-13.0;-0.2) beats/min lower than HDT. Overall, the intradialytic hemodynamic response was similar except for a trend towards higher peripheral resistance and central blood volume with LDT. There was a significantly greater fall in orthostatic systolic BP after dialysis compared with preHD, but there was no significant difference between interventions and the frequency of orthostatic hypotension postHD was also similar (HDT: 54% and LDT: 43%; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.57).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eCooler vs. standard dialysate temperature resulted in significantly higher intradialytic BP but had no significant impact on orthostatic BP response postHD.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e\u003cp\u003eThe study was registered at ClinicalTrials.gov where the full study protocol is available (NCT05052151). Registration date was 26/08 2021.\u003c/p\u003e","manuscriptTitle":"Hemodynamic effects of low versus high dialysate temperature in hemodialysis patients: a single-blinded, randomised, cross-over study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 09:58:26","doi":"10.21203/rs.3.rs-7251357/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-31T06:50:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-21T21:52:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"125934010802322165488799610518794003953","date":"2025-12-14T08:19:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-01T18:39:40+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246862533257363656699875631081497223143","date":"2025-11-26T19:18:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-12T12:52:47+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-06T07:28:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-04T12:58:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-04T12:58:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-07-30T09:43:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"886b3e68-8ac0-45cb-a5b0-17354407f170","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-10T07:09:58+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 09:58:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7251357","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7251357","identity":"rs-7251357","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}