Dialysate Sodium Prescription Research Articles

#1657 Impact of cumulative fluid and sodium imbalance exposure on cause-specific mortality in hemodialysis

Abstract Background and Aims Even mild fluid overload and prolonged exposure to salt excess showed to be associated with all-cause mortality in hemodialysis patients. This analysis aims to estimate the effect of fluid and sodium imbalance on cause-specific mortality. Method The study followed 68,196 incident hemodialysis patients from 875 clinics in 25 countries for a decade (2010-2020) using the European Clinical Database 5. Fatal events (21,644) were classified through ICD10- codes and free text descriptions into different endpoints: cardiac death (7,926 events)—with subcomponents sudden cardiac death (2,815 events), coronary death (1,705 events) and heart failure death (3,248 events); cerebrovascular death (1,516 events), non-cardiovascular death (10,898 events)—with subcomponents death by sepsis (2,054) or other infection (1,217 events), cancer death (2,095), other non-cardiovascular death (5,532 events) and death of unknown origin (1,304 events). Time-varying cumulative exposure times (in months) of relative fluid overload/-depletion, hypo-/hypernatremia and low dialysate sodium (≤ 138) were assessed and hazard ratios (HR) were calculated using a multivariate Cox model. Results Fluid overload showed the most consistent exposure risk associations for cardiovascular endpoints with strongest associations in cardiac causes (arrythmia death: HR peak at 7.5 (95% CI: 4.2-3.6), heart failure death: HR peak at 4.2 (95% CI: 3.3-5.4) and sudden cardiac death: HR peak at 3.8 (95% CI: 2.6-4.5)). Fluid depletion was less important but consistently associated with all causes of death. By contrast, Hyponatremia showed heterogeneity of cause specific effects. We found slightly stronger associations for non- cardiovascular causes: Death by sepsis (HR peak at 2.3 (95% CI: 1.8-2.8)) or death by other infections (HR peak at 2.1 (95% CI: 1.6-2.7)) showed the strongest cumulative exposure risk association pattern. Hypernatremia was less important with substantially smaller effects and slightly higher associations for non-cardiovascular endpoints. For low dialysate sodium, we observed evidence of heterogeneity in cause specific effects. The risk of death due to heart failure was notably pronounced with low dialysate sodium (HR peak at 5.8 (95% CI: 1.9-17.9)), while other endpoints did not show this effect. Sensitivity analysis in patients with 48 or more months of follow-up indicated that HR in higher exposure categories might be biased downwards due to non-survival of high-risk individuals. Conclusion Cause-specific hazard models confirm the role of fluid and sodium imbalance as independently acting risk factors for mortality. Fluid overload has the most pronounced effect on cardiac death, especially death by heart failure, arrhythmia, or sudden death. In contrast, hyponatremia is a more critical risk factor for non-cardiovascular death, particularly death caused by sepsis or other infections. The significantly increased risk in patients on low dialysate sodium prescriptions is primarily driven by a dramatic increase in risk of death by heart failure.

#496 Individualized approach in dialysate sodium prescription—safe and effective

Abstract Background and Aims The management of Na+ levels in hemodialysis (HD) patients plays a crucial role in maintaining their overall health and well-being. Na+, an essential electrolyte, is responsible for maintaining fluid balance, nerve function, and muscle contraction. However, in end-stage renal disease (ESRD) patients undergoing HD, Na+ imbalances are common and can have detrimental effects on their cardiovascular health. Furthermore, HD patients have been prescribed a standardized dialysis bath Na+ concentration (dNa+) during their HD sessions. The individualized approach aims to optimize Na+ balance, minimize adverse effects, and improve patient outcomes. Additionally, dietary Na+ intake, fluid status, and interdialytic weight gain (IDWG) also influence Na+ levels and should be considered when determining the appropriate Na+ prescription. The study aimed to assess whether an individualized dNa+ prescription can contribute to lower IDWG, expressed as a percent of prescribed dry weight (IDWG%). Method This retrospective, non-interventional study included all >18-year-old patients undergoing hemodialysis for >90 days at a single center. Patients were followed for a period of 18 months (December 2021–June 2023), during which the dNa+ concentration was gradually changed, as part of routine clinical care, until a gradient between plasma and dialysis bath Na+ of −2 mEq/L was achieved. Plasma Na+ levels were measured once monthly before a dialysis session along with other parameters such as IDWG and blood pressure. Results A total of 79 patients were enrolled in the study. The average age of the patients was 63.33 ± 12.1 years, with 43 (54.4%) being male. At baseline, the average duration of HD treatment was 255 ± 2.36 minutes, and the mean blood pump rate was 384.7 ± 42.81 ml/min. The majority of patients (98.8%) received HD treatments thrice weekly. Starting from January 2022, the mean dNa+ concentration decreased non-significantly from 139.39 ± 0.96 mmol/L to 138.99 ± 3.18 mmol/L, p = 0.13. The mean plasma Na+ concentration increased from 133.25 ± 2.9 to 136.59 ± 3.47 mmol/L, p < 0.00001, and while mean systolic blood pressure increased slightly (118.38 ± 12.25 to 122.87 ± 12.43, p = 0.01), it remained well controlled. The mean IDWG% decreased from 3.53 ± 1.34%, to 2.74 ± 1.35%, p = 0.35 and the proportion of patients with IDWG >5% decreased remarkably by more than half (11.4% to 5.1%), but due to the low patient numbers, the finding did not quite reach significance (p = 0.15, Table 1). Conclusion Our study demonstrates that individualized dNa+ management in HD patients is a beneficial approach, contributing to a decrease in the proportion of patients with severe IDWG increase, thereby addressing a crucial cardiovascular risk factor. Systolic blood pressure before dialysis remained well controlled, despite a slight, but significant increase. Our findings underscore the safety and potential benefits of an individualized approach to dialysate Na+ concentration, encouraging further exploration for enhanced HD patient care and increased overall well-being.

#3528 DIALYSATE SODIUM: IS IT STILL MYTH OR NOT?

Abstract Background and Aims Pre-hemodialysis serum sodium levels can vary among patients, therefore, a single dialysate sodium prescription may not be appropriate for all patients. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of prescription of different models of dialysate sodium. Method 77 nondiabetic subjects performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration set up at 138 mmol/L, followed by additional 4 models of dialysate sodium (each one 4 months sessions lasted) wherein dialysate sodium was set up: model 1: according to pre-hemodialysis serum sodium concentration, model 2: sodium concentration in UF fluid, model 3: sodium profiling (144-136 mmol/L, every hour decreasing of dialysate sodium during dialysis), model 4: stepwise dialysate sodium (starting dialysis with a dialysate sodium of 138 mmol/L and reducing it every week by 1 mmol/L sodium for the next 4 weeks). Blood pressure (BP), interdialytic weight gain (IDWG), thirst score, sodium gradient were analysed. After the standard dialysate sodium hemodialyses, the subjects were divided into normotensive, hypertensive and hypotensive based on the average pre-hemodialysis systolic BP during the standard dialysate sodium hemodialyses. Results Model 1: resulted in significantly lower BP (153.60±14.26 versus 133,61±11.88 mmHg; p = 0.000) and IDWG (2.21±0.93 versus 1.87±0.92 kg; p = 0.018) in hypertensive patients, whereas normotensive patients showed only significant decrease in IDWG (p = 0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p<0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. Thirst score was significantly lower in all patients with individualized-sodium HD and no relationship between the sodium gradient and the subjective feeling of thirst was confirmed (p = 0.368). Model 2: resulted in significantly lower BP in normotensive and hypertensive patients, with no influence on IDWG and thirst score compared to standard dialysate sodium (p = 0.474 and p = 0.212, retrospectively). Patients who were hypotensive, due to frequent collapses and unmeasurable blood pressure values, as well as for ethical reasons, were excluded from analysis with this dialysate sodium model. Model 3: confirmed significantly higher BP and IDWG in all 3 groups (p = 0.006) and significantly higher thirst score in normo and hipotensive patients (p = 0.000), with no influence in hypertensive patients. Model 4: significant decrease in SBP and DBP in hypertensive patients and insignificant increase in IDWG, but with no effects in normotensive and hypotensive patients on BP, IDWG and thirst score. Conclusion Model 1 resulted in better clinical outcome in hypertensive and normotensive patients compared to standard dialysate sodium, whereas other 3 models didn't show any clinical benefits.

Clinical impact of personalized sodium prescriptions in hemodialysis

Dialysate sodium prescription is often standardized. In some patients, this can be hypernatremic compared to serum sodium, causing a positive sodium balance at the end of treatment that will contribute to increased extracellular volume and interdialytic weight gain. A prospective study was carried out to monitor and compare the clinical implications between different prescriptions of sodium dialysate (isonatremic versus hyponatremic hemodialysis). For that purpose, we included hemodialysis patients in treatment for at least 9 months. The individual sodium setpoint was determined through the median of pre-dialysis sodium measurements, carried out for 6 treatments. The prescribed dialysate sodium was equal to the setpoint (isonatremic period) for 4 weeks and then 2 meq/L inferior to the setpoint (hyponatremic period) for another 4 weeks. The main outcome was interdialytic weight gain. Secondary outcomes were ultrafiltration rate, blood pressure at the beginning of treatment, intradialytic complications, and qualitative assessment of symptoms. Twenty patients were included. Pre-dialysis serum sodium assessments in both periods tended to be patient specific with a stable value. The interdialytic weight gain was lower in the hyponatremic period (1.83±0.50 kg versus 2.04±0.58 kg) but without statistical significance (p value=0.387). The same trend was found in mean ultrafiltration and blood pressure. Dialysis complications were low in both periods. The percentage of cramps and hypotension requiring intervention was higher in the hyponatremic period with no statistically significant differences. Concerning thirst, there was a symptomatic improvement with sodium customization. This improvement was even more significant in the hyponatremic period. This study allowed us to reinforce the existence of a “sodium setpoint” for each patient and the importance of an individualized dialysis prescription. Our results suggest the safety of using isonatremic hemodialysis with improving patients’ symptoms. Regarding hyponatremic hemodialysis, despite being beneficial, it seemed to be associated with a higher number of complications.

Opinion on the (Hemo)dialysate Sodium Prescription: Dialysate Sodium Prescription Should Not Be Considered in Isolation

With advances in hemodialysis technology and the desire to achieve cardiovascular stability during dialysis, prescribed dialysate sodium concentration has gradually increased over the years. Short-term trials suggest low dialysate sodium (<138 mEq/L) is beneficial in reducing interdialytic weight gain, pre- and post-dialysis BP, and predialysis serum sodium; but it increases intradialytic hypotensive episodes. We believe dialysate sodium prescription cannot be considered in isolation. Our approach is to use patient symptoms, meticulous fluid volume management and low temperature dialysate in conjunction with neutral dialysate sodium in managing our dialysis patients. Long-term trials are needed to inform optimum dialysate sodium prescription.

A Personal and Practical Answer from a Clinical Perspective

Restoring sodium and fluid homeostasis in hemodialysis (HD) patients is a crucial aim to reduce cardiovascular burden and improve global outcome. This crucial target is achieved at maximum in one quarter of HD patients according to a recent study. Sodium and fluid balance relies on a multitarget approach involving dietary salt restriction, dialysis salt mass removal and eventually residual kidney function. Salt mass removal in hemodialysis relies on ultrafiltration (convective sodium), the dialysate–plasma sodium gradient (diffusive sodium) and total treatment time. Manual dialysate sodium prescription has three major aims: dialysate–plasma sodium gradient; sodium mass removal target; hemodialysis tolerance and patient risks. In the future, automated dialysate sodium adjustment by HD machine will facilitate this aim.

Dialysate Sodium—One Size Unlikely to Fit All

The role of medical director of a hemodialysis unit has become increasingly complex. Among the many roles it encompasses, the delivery of safe and effective dialysis treatments requires constant review, synthesis, and interpretation of the medical literature. Despite decades of experience with hemodialysis, the evidence base for dialysate prescription is relatively limited, with the choice of dialysate sodium being a prime example. The ask of this exercise was to imagine ourselves as the medical director of a new hemodialysis unit and to consider factors influencing the choice of dialysate sodium. While fiscal considerations are indeed important, one hopes that these align with the delivery of clinical care to improve patient well-being. Therefore, my approach was to focus on exploring the clinical responsibilities of a medical director in the choice of dialysate sodium. As such, after reviewing the evidence to date, my ‘default’ dialysate sodium prescription would be 140 mmol/L, but I would retain the option of individualizing treatment for certain patients until further evidence becomes available.

Relationship between measured and prescribed dialysate sodium in haemodialysis: a systematic review and meta-analysis.

Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI) -1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (β = 1.16, 95% CI 1.06-1.27; P < 0.0001). A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing.

P1051WHICH MODEL OF DIALYSATE SODIUM PRESCRIPTION TO CHOOSE?

Abstract Background and Aims The dialysate sodium prescription remain unclear as an important component of sodium balance in HD patients Pre-hemodialysis (pre-HD) serum sodium levels can vary among different patients, therefore, a single dialysate sodium prescription may not be appropriate for all patients. Dialysate sodium is one of the most easy changeable parameter which can influence hemodynamic stability. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of prescription of different models of dialysate sodium Method 77 nondiabetic subjects (41 men; 36 women) performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration set up at 138 mmol/L, followed by additional 3 models of dialysate sodium (each model performed 2 months sessions with 2 months standard dialysate sodium between each model) wherein dialysate sodium was set up: model 1: according to pre-HD serum sodium concentration, model 2: according to sodium concentration in UF fluid, model 3: sodium profiling ( from 144 to 136 mmol/L). Blood pressure (BP), interdialytic weight gain (IDWG), thirst score, sodium gradient were analysed. After the standard dialysate sodium hemodialyses, the subjects were divided into 3 groups: normotensive (N=58), hypertensive (N= 14) and hypotensive (N=5) based on the average pre-HD systolic BP during the standard dialysate sodium hemodialyses. Results Model 1: resulted in significantly lower blood pressure (133,61±11.88 versus 153.60±14.26 mmHg; p=0.000) and IDWG (2.21±0.93 versus 1.87±0.92 kg; p=0.018) in hypertensive patients, whereas normotensive patients showed only significant decrease in IDWG (2.21±0.72 versus 2.06±0.65, p=0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p&amp;lt;0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. Thirst score was significantly lower in all patients with individualized-sodium HD and the use of antihypertensive drugs significantly reduced in hypertensive patients during the individualized phase. Model 2: resulted in significantly lower BP in normotensive and hypertensive patients (126.92±9.71 versus 124.08±8.71 mmHg; p=0.000; 153.60±14.26 versus 138.91±8.48 mmHg, accordingly), with no influence on IDWG, thirst score compared to standard dialysate sodium. Model 3: significantly higher BP and IDWG in all 3 groups (normotensive 126.92±9.71 versus 130.20±9.5 mmHg; p=0.001; IDWG 2.21±0.72 versus 2.34±0.82 kg, p=0,005; hypertensive 153.60±14.26 versus 157.58±5.0 mmHg; IDWG 2.21±0.93 versus 2.39±0.74 kg; p=0.005; hipotensive 79.81±11.78 versus 91.09±24.98 mmHg, IDWG 2.53±0.57 versus 2.73±0.15 kg, p=0.005) and significantly higher thirst score in normotensive and hypotensive patients, with no influence in hypertensive patients. Conclusion A reduction of the dialysate sodium concentration based on the pre HD serum sodium level of the patient, reduced the BP, IDWG, thirst score and use of antihypertensive drug compare to dialysate sodium according to sodium concentration in UF or sodium profiling. We recommend prescription of dialysate sodium according to pre HD serum sodium concentration.

P1081DIALYSATE SODIUM ALLIGNMENT AND SODIUM SET-POINT STABILITY IN HEMODIALYSIS PATIENTS: TWO-YEAR OBSERVATION

Abstract Background and Aims The low dialysate sodium (NaD) reduces intradialytic weight gain (IDWG) and blood pressure (BP), which are associated with improved outcomes. However, the intervention probably also increases intradialytic hypotension and reduces serum sodium (NaS), that are associated with increased mortality risk, so NaD should be individualized and brought closer to NaS. Predialysis natraemia in hemodialysis (HD) patients is considered constant (set-point) but some observations contradict this statement. The significance of clinical parameters, dialysis parameters and body water distribution is not clear. Method We undertake the retrospective observation among 45 HD patients for 24 months before large-scale prospective intervention investigation for individualization of NaD. We used two-year routinely monthly fixed data: NaS, NaD, IDWG, frequency of intradialysis hyper- and hypotension and seizures, peri- and intradialysis BP, home BP estimates, clinically and by bioimpedance estimated dry weight, ultrafiltration rate, frequency and duration of HD sessions. Results We included 27 males and 18 females of 60 (34-83) years old, with median HD vintage of 63 (29÷93) months. 1048 NaS measurements revealed mean natraemia of 137.1±2.8 (Q5-Q95 132-141) mmol/l (corrected for glucose). No differences in mean NaS according to gender, age, HD vintage, cardiac or liver dysfunction and residual renal function were found. Intraindividual NaS mean varied from 132 to 141 mmol/l and median of coefficient of variation (CV) was 1.4% (1.2÷1.6) (range 0.9-2.0%) which could be attributed mainly to measurement accuracy. The intraindividual NaS Q10-Q90 did not exceed 6 mmol/l with its median 3.0 (2.7÷3.7). Among whole group we revealed slow decreasing NaD trend (-0.12 mmol/l per year, R?0.45) which was accompanied by more prominent trend in systolic BP (-3.3 mmHg/year, R?0.64) and diastolic BP (-1.6 mmHg/year, R?0.49). In parallel, the frequency of intradialytic hypotension increased by 1.6 episodes/100HD per year (mean 2.3±0.6 after excluding the trend). 33 patients (73%) showed no significant individual trend in NaS (&amp;lt;1 mmol/l per year) for 24 months, 8 (18%) demonstrated decreasing trend (mean -1.5 mmol/l per year) while only 4 (9%) - increasing trend (mean +1.6 mmol/l per year). We observed no trend in prescribed bicarbonate level in dialysate. There were no significant associations between intraindividual deviations from individual mean weight before HD and from mean individual NaS. In whole group, intraindividual variations in NaS had no link with mean NaS. We observed the significant variations in NaS only in patients with large CV of predialysis weight (Q90-Q10&amp;gt;5 kg over 2 years). Overall mean of sodium serum to dialysate gradient (NaG) was slightly positive (+0.15±3.0 mmol/l) while 58% of patients had negative or neutral NaG. The latter had lesser IDWG but no difference in intradialytic hypotension frequency. We evaluated the number of random consecutive monthly predialysis NaS need to get acceptable estimation of real mean two-year predialysis NaS: five values gave 94% hit in range -1÷ +1 mmol/l. Conclusion Serum sodium is stable over time in HD patients with the only exception of patients with large intraindividual predialysis weight variation. Pre-HD serum sodium may be used as a parameter for individualizing dialysate sodium prescription.

Individualized dialysate sodium prescriptions using sodium gradients for high-risk hemodialysis patients lowered interdialytic weight gain and achieved target weights.

Large interdialytic weight gain (IDWG) is associated with increased morbidity and mortality in chronic hemodialysis patients. Over 50% of patients at our inner city tertiary academic center dialysis unit had IDWG and target weights (TW) above goal. We conducted an open-label nonrandomized study to explore the effects of an individualized dialysate sodium (DNa) prescription using Na gradients in patients at high risk for large IDWG. Thirty-three patients receiving chronic hemodialysis received individualized DNa prescriptions with a DNa bath of 0 to -2 meq/L below their serum Na level in the intervention group, while patients in the control group were prescribed the standard dialysate Na at 138 mmol/L. Serum Na level, predialysis SBP, symptomatic hypotensive episodes, and %hemodialysis treatments with large IDWG (%TxAIDWG) and above TW(%TxATW) were recorded before and three months after the intervention. We used student t tests to compare continuous variables and Chi-square tests to compare binary variables between the groups at baseline and after the intervention. Age- and sex-adjusted linear regression models were also constructed to assess the differences in each continuous outcome between the groups. Multivariable logistic regression models were conducted by modeling IDWG decrease and above estimated-dry-weight (EDW) decrease as binary dependent variables with adjustment for age, sex, and EDW change. Patients with individualized DNa concentrations had 3.6 times greater odds of having lower IDWG than those with standard dialysate Na concentration. This significant association remained after adjustment for age, sex, and changes in EDW (OR: 3.63; 95% CI, 1.03-12.9). There was no difference in predialysis BP or symptomatic hypotensive episodes between the two groups. Individualized DNa prescriptions appeared to be well tolerated and may be effective for optimal fluid management in high-risk hemodialysis patients.

Effects of Individualized Dialysate Sodium Prescription in Hemodialysis - Results from a Prospective Interventional Trial.

Introduction:Individualized dialysate sodium prescription does affect weight gain, blood pressure (BP), and intradialytic complications. A prospective interventional trial (Dialysate Individualised Sodium (DISO) trial) was conducted to study this issue in Indian patients.Methods:Forty patients on thrice-weekly maintenance hemodialysis (HD) for at least 6 weeks were enrolled. The study was performed in two different phases. In the first phase, 12 consecutive HD sessions were done with a standard dialysate sodium concentration of 140 mEq/L. In the second phase, 12 consecutive HD sessions were done with dialysate sodium concentration set to individualized value (mean of pre-HD sodium concentration multiplied by Donnan coefficient of 0.95). Differences in pre- and post-HD sodium, interdialytic weight gain (IDWG), pre- and post-HD BP, thirst scores, and intradialytic adverse events during both phases were assessed.Results:The mean age of patients was 45.65 years (24 males, 16 females). The mean serum pre-HD sodium level was 138.7 ± 1.7 meq/L in the standard phase and 138.2 ± 2.6meq/L in the individualized phase (P = 0.229). In the standard phase, the mean IDWG was 2.64 ± 1.56 kg and 2.13 ± 0.99 kg in the individualized phase (P = 0.008). The mean pre-HD systolic BP was 138 ± 18 mmHg and 134 ± 17 mmHg in the standard and individualized phases (P = 0.008). There was no difference in intradialytic symptoms, hypotensive episodes or requirement of interventions. Hypertension episodes occurred at a mean value of 2.2 and 1.2 in the standard and individualized phases, respectively (P = 0.010).Conclusion:The use of individualized dialysate sodium level is safe and results in lower IDWG, pre-HD systolic BP, and intradialytic hypertension in patients on HD.

Zero Diffusive Sodium Balance in Hemodialysis Provided by an Algorithm-Based Electrolyte Balancing Controller: A Proof of Principle Clinical Study.

Restoring and controlling fluid volume homeostasis is still a challenge in contemporary end-stage kidney disease patients treated by intermittent hemodialysis (HD) or hemodiafiltration (HDF). This primary target is achieved by ultrafiltration (dry weight probing) and control of intradialytic sodium transfer (dialysate-plasma Na gradient). The latter task is mostly ignored in clinical practice by applying a dialysate sodium prescription uniform for all patients of the dialysis center but unaligned to individual plasma sodium levels. Depending on the patient's natremia, a positive gradient gives rise to intradialytic diffusive sodium load and postdialytic thirst. On the contrary, a negative gradient may cause unwanted diffusive sodium removal and intradialytic symptoms. To overcome these challenges, a new conductivity-based electrolyte balancing algorithm embedded in a hemodialysis machine with the aim to achieve "zero diffusive sodium balance" in HD and online HDF treatments was tested in the form of a prospective clinical trial. The study comprised two phases: a first phase with a conventional fixed-sodium dialysate (standard care phase), followed by a phase with the electrolyte balancing control (EBC) module activated (controlled care phase). The results show a reduction in the variability of the intradialytic plasma sodium concentration shift, but it is overlain by a small but statistically significant increase in the mean plasma sodium levels. However, no clinical manifestations were observed. This sodium load can be explained by the design of the algorithm based on dialysate conductivity instead of sodium concentration. Furthermore, the increase in plasma sodium can be corrected by taking into account the potassium shift during the treatment. This study showed that the EBC module incorporated in the HD machine is able to automatically individualize the dialysate sodium to the patient's plasma sodium without measuring or calculating predialytic plasma levels from previous laboratory tests. This tool has the potential to facilitate fluid management, to control diffusive sodium flux, and to improve intradialytic tolerance in daily clinical practice.

Blood pressure control in conventional hemodialysis.

Hypertension among patients on hemodialysis is common, difficult to diagnose and often inadequately controlled. Although specific blood pressure (BP) targets in this particular population are not yet established, meta-analyses of randomized trials showed that deliberate BP-lowering with antihypertensive drugs improves clinical outcomes in hemodialysis patients. BP-lowering in these individuals should initially utilize nonpharmacological strategies aiming to control sodium and volume overload. Accordingly, restricting dietary sodium intake, eliminating intradialytic sodium gain via individualized dialysate sodium prescription, optimally assessing and managing dry-weight and providing a sufficient duration of dialysis are first-line treatment considerations to control BP. If BP remains uncontrolled despite the adequate management of volume, antihypertensive therapy is the next consideration. Contrary to nonhemodialysis populations, emerging clinical-trial evidence suggests that among those on hemodialysis, β-blockers are more effective than agents blocking the renin-angiotensin-system (RAS) in reducing BP levels and protecting from serious adverse cardiovascular complications. Accordingly, β-blockade is our first-line approach in pharmacotherapy of hypertension. Long-acting calcium-channel-blockers and RAS-blockers are our next considerations, taking into account the comorbidities and the overall risk profile of each individual patient. Additional research efforts, mainly randomized trials, are clearly warranted in order to elucidate aspects of management that remain elusive in hypertensive dialysis patients.

Dialysate sodium and intradialytic hypotension.

Intradialytic hypotension (IDH) is a common complication in hemodialysis, particularly with the time and frequency constraints of standard session delivery in contemporary practice. High intradialytic weight gain (IDWG), high ultrafiltration rates (UFR), and frequent IDH are highly interlinked, and separately or together contribute to the high cardiovascular morbidity and mortality observed in the hemodialysis population. Using a lower concentration of sodium in the dialysate (D-Na) reduces sodium delivery to the patient during dialysis, and several studies reported the beneficial effect in controlling IDWG, UFR, and hypertension. On the other hand, high dialysate sodium is associated with more hemodynamic benefits in an unstable patient. The resulting sodium loading may, however, induce a vicious cycle of higher IDWG, requiring more rapid ultrafiltration, eventually contributing to intradialytic symptoms and hypotension. In this article, we review the available literature on fixed and profiled dialysate sodium prescriptions, and we recommend a tailored approach that considers the patient's status to optimize dialysis delivery.

The Dialysis Sodium Gradient: A Modifiable Risk Factor for Fluid Overload

Background: Fluid overload in patients on conventional hemodialysis is a frequent complication, associated with increased cardiovascular morbidity and mortality. The dialysate sodium prescription is a potential modifiable risk factor. Our primary objective was to describe associations between dialysate-to-serum sodium gradient and parameters of fluid status. A secondary objective was to evaluate the 6-month risk of hospitalization and mortality in relation to sodium gradient. Methods: We performed a cross-sectional study of 110 prevalent conventional hemodialysis patients at a single center. The associations of sodium gradient with interdialytic weight gain index (IDWG%), ultrafiltration (UF) rate, and blood pressure (BP) were analyzed. Results: The mean serum sodium gradient was 4.6 ± 3.6 mEq/L. There was a direct correlation between sodium gradient and IDWG% (r = 0.48, p < 0.01) as well as UF rate (r = 0.44, p < 0.01). In a logistic regression model, a 1 mEq/L higher sodium gradient was associated with increased risk of IDWG% >3% (OR 1.33, p < 0.01) and increased risk of UF rate >10 mL/kg/h (OR 1.16, p = 0.03), but there were no associations with intradialytic hypotension, intradialytic hypertension or BP. No significant differences were found with 6-month hospitalization or mortality risk in relation to sodium gradient. Conclusion: A higher sodium gradient was associated with significant increases in IDWG and UF rates, known to be associated with poor outcomes, but was not associated with intradialytic hypotension. Individualizing the dialysate sodium prescription to minimize sodium gap may lead to less fluid overload in conventional hemodialysis patients.

Effect of Personalized Dialysate Sodium Prescription on Plasma Sodium Concentration and Sodium Set Point in Conventional, Quotidian and Nocturnal Home Hemodialysis

Introduction and objectives: In thrice weekly conventional hemodialysis, dialysate sodium prescription can cause intradialytic plasma sodium shifts, and undesirable symptoms. However, changes in pre-dialysis plasma sodium setpoint are not observed. Whether these clinical observations are observed in quotidian or nocturnal home hemodialysis has not been prospectively evaluated. Methods: A randomized crossover study of conventional, quotidian and nocturnal home hemodialysis patients was performed. Dialysate sodium was personalized 3 mmol/L above (HIGHDIALSOD) or below (LOWDialSOD) the SP, with 100 days for each crossover studies period. Results: Plasma Na+ decreased during hemodialysis in LOWDialSOD study period (136.8 to 135.0 mmol/L, p=0.002). Pre-Na+ SP (137.4 to 136.8 mmol/L, p=0.03) and Pre-Na+ SP slope (0.014 to -0.015 mmol/L/day, p=0.009) decreased from HIGHDialSOD to LOWDialSOD study periods. Conclusions: Personalization of Dial-Na+ to below SP leads to reductions in plasma sodium concentration during hemodialysis, in conventional, quotidian and nocturnal home hemodialysis patients. Furthermore, sodium set point changes in response to Dial-Na+ prescription. This has the potential to lead to adverse outcomes in a patient population that is followed less frequently and stringently than the in-center hemodialysis population.

Comparison of Prescribed and Measured Dialysate Sodium: A Quality Improvement Project

There is controversy regarding the optimal dialysate sodium concentration for hemodialysis patients. Dialysate sodium concentrations of 134 to 138 mEq/L may decrease interdialytic weight gain and improve hypertension control, whereas a higher dialysate sodium concentration may offer protection to patients with low serum sodium concentrations and hypotension. We conducted a quality improvement project to explore the hypothesis that prescribed and delivered dialysate sodium concentrations may differ significantly. Cross-sectional quality improvement project. 333 hemodialysis treatments in 4 facilities operated by Dialysis Clinic, Inc. Measure dialysate sodium to assess the relationships of prescribed and measured dialysate sodium concentrations. Magnitude of differences between prescribed and measured dialysate sodium concentrations. Dialysate sodium measured pre- and late dialysis. The least square mean of the difference between prescribed minus measured dialysate sodium concentration was -2.48 (95% CI, -2.87 to -2.10) mEq/L. Clinics with a greater number of different dialysate sodium prescriptions (clinic 1, n=8; clinic 2, n=7) and that mixed dialysate concentrates on site had greater differences between prescribed and measured dialysate sodium concentrations. Overall, 57% of measured dialysate sodium concentrations were within ±2 mEq/L of the prescribed dialysate sodium concentration. Differences were greater at higher prescribed dialysate sodium concentrations. We only studied 4 facilities and dialysate delivery machines from 2 manufacturers. Because clinics using premixed dialysate used the same type of machine, we were unable to independently assess the impact of these factors. Pressures in dialysate delivery loops were not measured. There were significant differences between prescribed and measured dialysate sodium concentrations. This may have beneficial or deleterious effects on clinical outcomes, as well as confound results from studies assessing the relationships of dialysate sodium concentrations to outcomes. Additional studies are needed to identify factors that contribute to differences between prescribed and measured dialysate sodium concentrations. Quality assurance and performance improvement (QAPI) programs should include measurements of dialysate sodium.

It is Time to Individualize the Dialysate Sodium Prescription

Sodium mass balance in hemodialysis patients is primarily dependent on dietary salt intake and sodium removal during dialysis. One of the most important goals of dialysis therapy is to fully remove the mass of sodium that has accumulated in the interdialytic period. It is currently the practice in dialysis centers all over the world to use a standardized dialysate sodium concentration (Na(+) D) for all patients. The aim of the present article was to summarize the current evidence for an individualized Na(+) D prescription. Three main points are discussed: (i) Na(+) D prescription, which must necessarily take into account the sodium setpoint and the sodium gradient; (ii) clinical experience with an individualized Na(+) D prescription, and (iii) guidelines for individualizing the Na(+) D prescription. To summarize, recent data suggest that tailoring Na(+) D to an individual's sodium setpoint has the potential for short- and long-term benefits for patients. Prospective interventional studies are warranted to further understand its effects, stratified for patients with low or high serum sodium levels.

Dialysate Sodium: Choosing the Optimal Hemodialysis Bath

Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and is a major cause of hospitalizations. It is often addressed by reinforcing the importance of a low-salt diet with patients and challenging estimated dry weights. More recently, interest has shifted toward the dialysate sodium prescription as a strategy to improve fluid overload and its adverse sequelae. The availability of high-flux high-efficiency dialysis in conjunction with the need to ensure its tolerability for patients has resulted in an increase in dialysate sodium prescriptions from 120 to≥140 mEq/L. However, we are now tackling the unforeseen consequences associated with high dialysate sodium prescriptions. High dialysate sodium concentration is associated with high interdialytic weight gain, a commonly used surrogate for hypervolemia contributing to hypertension. The association between mortality and high dialysate sodium concentration remains controversial with conflicting data. It is clear that fluid management in the diverse end-stage renal disease population is extremely complex and more clinical trials are needed. In the meantime, while patients require treatments and clinical decisions need to be made, this review article attempts to summarize the current evidence for individualized dialysate sodium prescriptions based on patients' volume status, comorbid conditions, plasma sodium level, and hemodynamic response to dialysis therapy.