Higher Dialysate Sodium Concentrations Research Articles

Dialysate Sodium Levels, Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients.

Increased aortic blood-pressure(BP) and arterial stiffness are associated with higher cardiovascular risk in hemodialysis. Previous works showed that lower dialysate sodium is associated with lower brachial-BP; data on aortic-BP and arterial stiffness are limited. This study aimed to investigate the effects of different dialysate sodium concentrations on 72-h aortic-BP and arterial stiffness parameters in hemodialysis patients. This analysis is part of a prospective, non-randomized interventional study. Twenty-five hemodialysis patients underwent a set of three periods of different dialysate sodium concentrations; six sessions with dialysate sodium of 137meq/L, followed consecutively by six sessions with 139meq/L and, finally, six sessions with 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM (Mobil-O-Graph) was performed to evaluate aortic-BP and arterial stiffness indices during the overall 72-h, different 24-h, day-time and night-time periods. Mean 72-h aortic SBP/DBP were higher with increasing dialysate sodium concentrations (137meq/L: 114.2±15.3/77.0±11.8mmHg vs 139meq/L: 115.4±17.3/77.9±14.0mmHg vs 141meq/L: 120.5±18.4/80.5±14.7mmHg, p=0.002/p=0.057, respectively). Wave-reflections parameters (AIx, AIx(75), AP) were not significantly different between the three dialysate sodium concentrations. Ambulatory PWV was significantly higher with increasing dialysate sodium concentrations (137meq/L: 8.5±1.7m/s vs 139meq/L: 8.6±1.6m/s vs 141meq/L: 8.8±1.6m/s, p<0.001). In generalized linear-mixed-models including 72-h brachial SBP as random covariate, the adjusted marginal-means of 72-h PWV were not significantly different between-groups. This study showed that lower dialysate sodium concentrations are associated with significant decreases in ambulatory aortic BP and PWV. This study showed that higher dialysate sodium concentrations are associated with significant increases in ambulatory aortic BP and PWV. These findings further support the need for modification of dialysate sodium concentration in hemodialysis.

#2887 Interdialytic weight gain and low dialysate sodium concentration in patients on chronic hemodialysis: a systematic review and meta-analysis

Abstract Background and Aims In many patients on chronic hemodialysis, interdialytic weight gain (IDWG) is greater than 4.0%-4.5% of dry weight, the value recommended by the international guidelines. High IDWG is a condition associated with risk of all-cause mortality and hospitalization and it depends on elevate intake of fluids and/or foods. More specifically, high intake of water is secondary to the disturbing and constant presence of thirst in such patients, so the limitation of the IDWG is a challenge both for the patients and the physicians. Low dialysate sodium levels can significantly reduce thirst as well as the water intake in the interdialytic period because they can increase the removal of sodium during the dialytic session, and this leads to a reduced content of sodium in the body. The present systematic review and meta-analysis aims at evaluating the efficacy of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients. Method Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: 1) Primary research studies in adult patients (over 18 years of age), 2) Included patients with end-stage renal disease on chronic hemodialysis since at least 6 months; 3) Compared standard (138-140 mmol/l) or high (&amp;gt;140 mmol/l) dialysate sodium concentration with low (&amp;lt;138 mmol/l) dialysate sodium concentration; 4) Included one outcome of interest: interdialytic weight gain. We excluded studies on pediatric patients, pre-dialysis CKD patients, acute kidney injury patients, ESRD patients with other renal replacement therapy modalities such as peritoneal dialysis and transplant. Medline, PubMed, Web of Science, and the Cochrane Library were searched for studies comparing low or high dialysate sodium concentration. Outcome of interest was IDWG. The quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. Results Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of −0.40 kg (95% CI -0.50 to −0.30; P &amp;lt; 0.00001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (P=0.05) reduction in one study, and not significant reduction in one study. In most studies, the frequency of intradialytic hypotensive events did not differ significantly between low and high sodium dialysate hemodialysis. The GRADE methodology was used to assess the quality of the body of retrieved evidence and studies risk of bias, inconsistency and imprecision were estimated as low. Conclusion Low dialysate sodium concentration reduces the IDWG in patients on chronic hemodialysis.

The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study.

Hypertension is associated with increased morbidity and mortality in hemodialysis patients. Existing recommendations suggest reduction of sodium load, but the effect of dialysate sodium on blood pressure (BP) is not fully elucidated. The aim of the present study is to investigate the effect of different dialysate sodium concentrations on 72-h ambulatory BP in hemodialysis patients. This prospective study included patients on standard thrice-weekly hemodialysis. All patients initially underwent six sessions with dialysate sodium concentration of 137meq/L, followed consecutively by another six sessions with dialysate sodium of 139meq/L and, finally, six sessions with dialysate sodium of 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM was performed over the long interdialytic interval to evaluate ambulatory systolic and diastolic BP (SBP and DBP) during the overall 72-h, different 24-h, daytime and night-time periods. Twenty-five patients were included in the final analysis. A significant increase in the mean 72-h SBP was observed with higher dialysate sodium concentrations (124.8±16.6mmHg with 137meq/L vs 126.3±17.5mmHg with 139meq/L vs 132.3±19.31mmHg with 141meq/L, P=0.002). Similar differences were noted for DBP; 72-h DBP was significantly higher with increasing dialysate sodium concentrations (75.1±11.3mmHg with 137meq/L vs 76.3±13.7mmHg with 139meq/L vs 79.5±13.9mmHg with 141meq/L dialysate sodium, P=0.01). Ambulatory BP during the different 24-h intervals, daytime and night-time periods was also progressively increasing with increasing dialysate sodium concentration. This pilot study showed a progressive increase in ambulatory BP with higher dialysate sodium concentrations. These findings support that lower dialysate sodium concentration may help towards better BP control in hemodialysis patients.

A randomized controlled trial of two dialysate sodium concentrations in hospitalized hemodialysis patients.

Several large dialysis organizations have lowered the dialysate sodium concentration (DNa) in an effort to ameliorate hypervolemia. The implications of lower DNa on intra-dialytic hypotension (IDH) during hospitalizations of hemodialysis (HD) patients is unclear. In this double-blind, single center, randomized controlled trial (RCT), hospitalized maintenance HD patients were randomized to receive higher (142 mmol/L) or lower (138 mmol/L) DNa for up to six sessions. Blood pressure (BP) was measured in a standardized fashion pre-HD, post-HD and every 15 min during HD. The endpoints were: (i) the average decline in systolic BP (pre-HD minus lowest intra-HD, primary endpoint) and (ii) the proportion of total sessions complicated by IDH (drop of ≥20 mmHg from the pre-HD systolic BP, secondary endpoint). A total of 139 patients completed the trial, contributing 311 study visits. There were no significant differences in the average systolic blood pressure (SBP) decline between the higher and lower DNa groups (23 ± 16 versus 26 ± 16 mmHg; P = 0.57). The proportion of total sessions complicated by IDH was similar in the higher DNa group, compared with the lower DNa group [54% versus 59%; odds ratio 0.72; 95% confidence interval (95% CI) 0.36-1.44; P = 0.35]. In post hoc analyses adjusting for imbalances in baseline characteristics, higher DNa was associated with 8 mmHg (95% CI 2-13 mmHg) less decline in SBP, compared with lower DNa. Patient symptoms and adverse events were similar between the groups. In this RCT for hospitalized maintenance of HD patients, we found no difference in the absolute SBP decline between those who received higher versus lower DNa in intention-to-treat analyses. Post hoc adjusted analyses suggested a lower risk of IDH with higher DNa; thus, larger, multi-center studies to confirm these findings are warranted.

Clinical Effects of Personalized Dialysate Sodium in Conventional, Quotidian, and Nocturnal Home Hemodialysis Patients: A Randomized Crossover Trial

Background: In thrice weekly conventional haemodialysis patients, higher dialysate sodium concentrations may associate with adverse clinical outcomes. Whether increased frequency and duration of haemodialysis in quotidian and nocturnal patients alters these clinical outcomes is unknown. Methods: A randomized crossover study was performed in conventional, quotidian and nocturnal haemodialysis patients. Dialysate sodium (Dial-Na+) was personalized 3 mmol/L above (DIALHighSOD) or below (DIALLowSOD) the pre-dialysis plasma sodium set point (SP), with 100 days for each crossover study period. Results: Interdialytic weight gain (IDWG)(2.15 vs. 1.90 L, p=0.002), IDWG as % of target weight (IDWG%)(2.78 vs. 2.39%, p=0.002), pre-dialysis systolic (143.3 vs. 138.3 mm Hg, p=0.001), diastolic (78.6 vs. 75.6 mm Hg, p=0.008) and mean arterial pressure (100.2 vs. 96.5 mm Hg, p=0.003), post-dialysis systolic (135.4 vs. 130.0 mm Hg, p=0.04), diastolic (75.8 vs. 72.4 mm Hg, p=0.006) and mean arterial pressure (95.7 vs. 91.6 mm Hg, p=0.009) were higher in DIALHighSOD than DIALLowSOD. Haemodialysis frequency was associated with decreased (R=-0.295, slope=-0.002, p=0.034) IDWG%, while the opposite was seen with haemodialysis duration (R=0.507, slope=0.002, p<0.001). Haemodialysis duration increased intradialytic change in diastolic blood pressure (R=0.280, slope=1.127, p=0.044), while haemodialysis frequency increased post-dialysis diastolic blood pressure (R=0.366, slope=3.464, p=0.008). Conclusions: These results confirm that dialysate sodium concentration alters clinical outcomes in quotidian and nocturnal haemodialysis patients, and that dialysis frequency and duration correlate in opposing fashions in IDWG. Further studies are required to determine the effect of dialysate sodium on cardiovascular outcomes. This trial is registered at UMI26102.

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.

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.

High versus low dialysate sodium concentration in chronic haemodialysis patients: a systematic review of 23 studies.

It is the object of debate whether a low or high dialysate sodium concentration (DNa(+)) should be advocated in chronic haemodialysis patients. In this paper, we aimed at evaluating benefits and harms of different DNa(+) prescriptions through a systematic review of the available literature. MEDLINE and CENTRAL databases were searched for studies comparing low or high DNa(+) prescriptions. Outcomes of interest were mortality, blood pressure (BP), interdialytic weight gain (IDWG), plasma sodium, hospitalizations, use of anti-hypertensive agents and intradialytic complications. Twenty-three studies (76 635 subjects) were reviewed. There was high heterogeneity in the number of patients analysed, overall study quality, duration of follow-up, DNa(+) and even in the definition of 'high' or 'low' DNa(+). The only three studies looking at mortality were observational. The risk of death was related to the plasma-DNa(+) gradient, but was also shown to be confounded by indication from the dialysate sodium prescription itself. BP was not markedly affected by high or low DNa(+). Patients treated with higher DNa(+) had overall higher IDWG when compared with those with lower DNa(+). Three studies reported a significant increase in intra-dialytic hypotensive episodes in patients receiving low DNa(+). Data on hospitalizations and use of anti-hypertensive agents were sparse and inconclusive. There is currently no definite evidence proving the superiority of a low or high uniform DNa(+) on hard or surrogate endpoints in maintenance haemodialysis patients. Future trials adequately powered to evaluate the impact of different DNa(+) on mortality or other patient-centred outcomes are needed.

Effect of Low Versus High Dialysate Sodium Concentration on Blood Pressure and Endothelial-Derived Vasoregulators During Hemodialysis: A Randomized Crossover Study

Intradialytic hypertension affects ∼15% of hemodialysis patients and is associated with increased morbidity and mortality. While intradialytic hypertension is associated with increases in endothelin 1 relative to nitric oxide (NO), the cause of these imbalances is unknown. Invitro evidence suggests that altering plasma sodium levels could affect endothelial-derived vasoregulators and blood pressure (BP). Thus, we hypothesized that compared to high dialysate sodium, low dialysate sodium concentration would lower endothelin 1 levels, increase NO release, and reduce BP. 3-week, 2-arm, randomized, crossover study. 16 patients with intradialytic hypertension. Low (5 mEq/L below serum sodium) versus high (5 mEq/L above serum sodium) dialysate sodium concentration. Endothelin 1, nitrite (NO2(-)), and BP. Mixed linear regression was used to compare the effect of dialysate sodium (low vs high) and randomization arm (low-then-high vs high-then-low) on intradialytic changes in endothelin 1, NO2(-), and BP values. The average systolic BP throughout all hemodialysis treatments in a given week was lower with low dialysate sodium concentrations compared with treatments with high dialysate sodium concentrations (parameter estimate,-9.9 [95% CI,-13.3 to-6.4] mm Hg; P< 0.001). The average change in systolic BP during hemodialysis also was significantly lower with low vs high dialysate sodium concentrations (parameter estimate,-6.1 [95% CI,-9.0 to-3.2] mm Hg; P< 0.001). There were no significant differences in intradialytic levels of endothelin 1 or NO2(-) with low vs high dialysate sodium concentrations. Carryover effects limited the power to detect significant changes in endothelial-derived vasoregulators, and future studies will require parallel trial designs. Low dialysate sodium concentrations significantly decreased systolic BP and ameliorated intradialytic hypertension. Longer studies are needed to determine the long-term effects of low dialysate sodium concentrations on BP and clinical outcomes.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Effect of gradually lowering dialysate sodium concentration on the interdialytic weight gain, blood pressure, and extracellular water in anuric hemodialysis patients

Background: The majority of hemodialysis (HD) patients are overhydrated and have high interdialytic weight gain (IDWG) which induces increased blood pressure (BP). The positive sodium balance resulting from a high sodium diet, a high dialysate sodium concentration (DNa), or a combination of both is major causes of this disease. We evaluated the effects of lowering DNa on IDWG, BP, and volume status in anuric HD patients with dietary sodium restriction. Methods: Thirty-two patients were enrolled in this study and the period was divided by phase 1 and 2 according to DNa which decreased from 140 to 135 mEq/L at a rate of 1 mEq/L per month; phase 1, 140 mEq/L; phase 2, 135 mEq/L. We compared the IDWG, BP, volume status measured by multifrequency bioimpedance spectroscopy, and adverse events such as intradialytic hypotension, cramps, and headache of both phases. Results: The IDWG was significantly reduced by 0.39 ± 0.38 kg (p = 0.000). Pre-dialysis BP showed significant reduction (systolic pressure 146 ± 18 vs. 138 ± 22 mmHg; p = 0.012, diastolic pressure 80 ± 10 vs. 75 ± 11 mmHg; p = 0.008). Pre-dialysis extracellular water (ECW) was reduced significantly by 0.13 ± 2.22 L (p = 0.02). There was no significant increase in adverse events (all p > 0.05). Conclusions: This study showed that gradually lowering DNa could bring a significant reduction in pre-dialysis IDWG, BP, and ECW without increased adverse events. Large and crossover designed study will be needed to demonstrate the clear causal relationship.

Dialysate sodium, serum sodium and mortality in maintenance hemodialysis

Individuals with end-stage kidney disease appear to have stable pre-dialysis serum sodium concentrations over time, with lower values associating with increased mortality. Dialysate sodium concentrations have increased over many years in response to shorter treatments, but the relationship between serum sodium, dialysate sodium and outcomes in chronic hemodialysis patients has not yet been systematically examined. We studied a cohort of 2272 individuals receiving thrice-weekly hemodialysis treatment. Available data included demographics, laboratory and clinical measures, details of the dialysis prescription and 30-month follow-up. We examined the distribution of serum and dialysate sodium among subjects and compared mortality according to dialysate and serum sodium concentrations using Cox regression models. Dialysate sodium concentration varied within and among dialysis centers. The pre-dialysis serum sodium concentration (mean 136.1 mmol/L) did not differ across dialysate sodium concentrations. There was evidence for effect modification for mortality according to differing serum sodium and dialysate sodium concentrations (P=0.05). For each 4 mmol/L increment in serum sodium, the hazard ratio for death was 0.72 [95% confidence interval (CI) 0.63-0.81] with lower dialysate sodium compared to 0.86 (95% CI 0.75-0.99) for higher dialysate sodium. Higher dialysate sodium concentration was associated with mortality at higher, but not lower, pre-dialysis serum sodium concentrations. The pre-dialysis serum sodium concentration appears to be unaffected by the dialysate sodium concentration. The relationship between serum and dialysate sodium and mortality appears to be variable. Further research is warranted to determine the biological mechanisms of these associations and to re-examine total body sodium handling in hemodialysis.

Ionic mass balance and blood volume preservation during a high, standard, and individualized dialysate sodium concentration.

Although a higher dialysate sodium concentration (DNa) is frequently used to improve haemodynamic stability during haemodialysis, few studies have compared ionic mass balance (IMB) during different DNa. Moreover, DNa is usually a standard prescription, whereas inter-individual pre-dialytic serum sodium levels may differ widely. The aims of the study were to assess IMB and the decline in blood volume (DeltaBV) during isovolaemic HD as well as during HD combined with ultrafiltration (UF) during DNa [140], DNa [144], and an individualized DNa [ind], in which DNa is equal to pre-HD plasma conductivity x 10. IMB and plasma conductivity were assessed by on-line conductivity measurements (Diascan; Hospal) in 13 HD patients. After 1 h of isovolaemic HD, measurements were continued during UF+HD until dry weight. DeltaBV was assessed by an optical method (Hemoscan). During isovolaemic HD with DNa [140] and [144], Pre-Na was significantly related to IMB (r=0.83 and r=0.61; P<0.05). Diffusive Na flux into the patient occurred when the difference between DNa and pre-dialytic serum sodium was larger than 5 mmol/l. During UF+HD, IMB was 318+/-166 mmol during DNa [140], 277+/-116 mmol during DNa [ind], and 239+/-111 during DNa [144] (mean+/-SD; P<0.05 compared with the other treatment modalities) whereas DeltaBV did not differ significantly. In the five patients with a pre-dialytic sodium concentration below 140 mmol/l, ionic removal was significantly higher during DNa [ind] (324+/-87) compared with DNa [140] (228+/-127 mmol; P<0.05) without a significant difference in DeltaBV (-9.7+/-1.6 vs -7.8+/-2.3%). A large difference in IMB was observed between DNa 144 and DNa 140, without a significant difference in DeltaBV. In patients with low pre-dialytic serum sodium levels, diffusive ionic influx from the dialysate into the patient may occur. In patients with low pre-dialytic sodium levels, DNa [ind] leads to an enhanced ionic removal compared with DNa [140] without large differences in DeltaBV.

Simulation study of the intercompartmental fluid shifts during hemodialysis.

Hypotension is the most frequent complication during hemodialysis. An important cause of hypotension is a decrease in the intravascular volume. In addition, a decrease in plasma osmolality may be a contributing factor. Modeling of sodium and ultrafiltration (UF) may help in the understanding of underlying relationships. We therefore simulated, in a mathematical model, the intercompartmental fluid shifts during standard hemodialysis (SHD), diffusive hemodialysis (DHD), and isolated ultrafiltration (IU). We analyzed the relative theoretical effect of hydration status, dialysate sodium concentration, the initial plasma concentrations of sodium and urea, and tissue permeation to solutes on the magnitude and direction of intracellular and intravascular volume changes. This theoretical analysis shows that the transcellular fluid shifts taking place during hemodialysis treatment are, to a great part, due to inhomogeneous distribution of regional blood flow and tissue fluid volumes. During hemodialysis treatment, the cellular fluid shifts in tissue groups with relatively high perfusion and small volume occur from the intra- to the extracellular spaces. However, the fluid shift in tissue groups with a low perfusion and large volume takes place in the opposite direction. The UF volume and rates, and the size of the sodium (Na+) gradient between the dialysate and blood side of the dialyzer membrane are the most important factors influencing the fluid shifts. Higher UF volumes and flow rates cause an increasing decline in the plasma volume in both SHD and IU. High dialysate sodium concentration (150 mEq L(-1)) helps plasma refilling slightly when compared with a normal dialysate sodium concentration (140 mEq L(-1)). However, a high dialysate sodium concentration is associated with a high plasma sodium rebound, which in turn may lead to interdialytic water intake resulting from thirst and may cause increased weight gain and hypertension.

The Renin–Angiotensin–Aldosterone System During Haemodialysis With Acetate or Bicarbonate at Different Dialysate Sodium Concentrations

The hormones of the renin angiotensin aldosterone system were measured during regular haemodialysis with acetate or bicarbonate at dialysate sodium concentrations of 135, 140, 145, and 150 mmol/l. Plasma renin activity and aldosterone concentration were higher during acetate haemodialysis than during bicarbonate haemodialysis. At lower dialysate sodium concentrations, plasma renin activity (acetate dialysis and bicarbonate dialysis) and aldosterone concentration (only acetate dialysis) were higher than they were at higher dialysate sodium concentrations. Plasma renin activity increased during acetate dialysis, but did not change during bicarbonate dialysis. Aldosterone and potassium concentrations were positively correlated. Aldosterone decreased during haemodialysis (increase to predialysis values at the end of haemodialysis (4 h) at lower dialysate sodium concentrations). It is concluded that the renin angiotensin aldosterone system is activated more during acetate dialysis than during bicarbonate dialysis. Aldosterone concentrations seem to be related more closely to serum potassium than to renin-angiotensin-aldosterone system and to serum sodium intradialytically.

Multivariate biochemical analysis of amniotic fluid

Six stable chronic hemodialysis patients received six hemodialysis treatments: two each with the dialysate sodium concentration (DNa) 7% greater than serum sodium concentration, two with a DNa equal to serum sodium concentration and two with the DNa 7% less than the serum sodium concentration. During one treatment with each dialysate 2 kg of fluid was removed and during the other treatments the patient's weight was kept constant. Total body water (TBW), intracellular water (IM), extracellular water (ECW), plasma volume (PV), plasma renin activity (PRA), aldosterone (ALDO), Na, BUN and osmolality were determined before and after each treatment. Fluid removal during dialysis had no effect on ICW with essentially all the fluid removed during dialysis coming from ECW. ICW increased with low DNa and decreased with high DNa The effect of DNa on ECW and PV was the opposite of that on ICW. PRA increased and ALDO decreased during dialysis. Predialysis ALDO directly correlated with PRA (r = 0.68, p < 0.001) but not with serum potassium concentration. Post dialysis ALDO was not significantly correlated with either PRA or potassium. Fluid removal and low DNa increased both PRA and ALDO. These studies indicate that water shifts from the extracellular space into intracellular space when DNa is lower than serum Na and the reverse is true when DNa exceeds serum Na. Plasma aldosterone decreases during dialysis despite an increase in PRA, possibly related to the decrease in serum potassium concentration. The effect of fluid removal and low DNa on PRA and ALDO may be related to a reduction in ECW and/or PV.

A critical examination of dialysis-induced hypotension.

Dialysis-induced hypotension has received considerable attention recently because of its high incidence of occurrence. Several factors have been proposed as etiologic mechanisms. They include hypovolemia, autonomic dysfunction, decreasing serum osmolality, vasodilation (or the inhibition of compensatory vasoconstriction), efficiency of diffusive solute transport, depletion of vasoactive substances and blood gas and acid-base changes. The primary determinants of blood pressure being cardiac output and total peripheral resistance, the magnitude and direction of change of these two parameters determines the blood pressure response. If the rate of ultrafiltration exceeds the rate of vascular refilling, hypovolemia results. Intracellular fluid shifts secondary to preferential solute removal from the extracellular space may compromise vascular refilling and contribute to hypovolemia. If the hypovolemia is not compensated for by increases in heart rate or stroke volume, the cardiac output falls. Autonomic dysfunction, a previous history of myocardial infarction or impaired tissue oxygenation secondary to hypoxia may limit compensatory increases in heart rate and stroke volume. Even if the cardiac output falls, if compensatory vasoconstriction is elicited, blood pressure can be maintained. The experimental evidence suggests that the diffusive aspect of dialysis therapy plays an important role in inhibiting compensatory vasoconstriction. Such inhibition is not observed with hemofiltration, a therapy based on convective rather than diffusive solute removal. While autonomic dysfunction and the diffusive removal of vasoactive substances may play a role in inhibiting the vasoconstrictive response, the use of acetate as a buffer source and the decreasing serum osmolality seem to be of greater importance. Acetate produces vasodilation. It also has a positive inotropic effect. Studies suggest that the vasodilation produced by acetate is compensated for by a proportionate increase in cardiac output except during the early stages of the therapy when the fall in total peripheral resistance may overwhelm the increase in cardiac output. The substitution of bicarbonate for acetate results in a decrease in the incidence of symptomatic hypotension in some patients. This alleviation of symptoms appears to be significant only when the dialystate sodium concentration is relatively low (130–135 m M ). At higher dialysate sodium concentrations (140–145 m M ), the blunting of the fall in serum osmolality seems to be of greater importance than the nature of the buffer source in reducing the incidence of symptomatic hypotension. It is not clear if blunting the fall in serum osmolality has a greater beneficial influence on the cardiac output or on the total peripheral resistance. While the etiology of dialysis-induced hypotension is complex, controversial, and multifactorial, amelioration of symptomatic hypotension with a higher dialysate sodium concentration offers a practical solution. The substitution of bicarbonate for acetate is a technically more complex and expensive alternative.

Controversy in renal disease: dialysis-induced hypotension.

HEMODIALYSIS is remarkably safe. Death due to technical failure or humanerror occurs in only about 1 in 75,000 treatments. The resilience of the cardiovascular system can be appreciated from its ability to tolerate hours of extracorporeal blood circulation at flow rates of 300 mVmin or greater. Very few patients develop true shock during or as an immediate consequence of hemodialysis. A substantial proportion, however, become hypotensive to the extent that postdialysis malaise limits prompt return to predialysis physical activities in many otherwise well rehabilitated patients. Little attention was devoted to the understanding of dialysis-induced hypotension in the first decade of maintenance hemodialysis perhaps, because patient and physician viewed this complication as an unavoidable side effect of a wondrous new therapy. Subsequently, lessons learned in the mid 1970s, from clinical trials of postdilutional hemofiltration, and reexploration of the utility of bicarbonate (rather than acetate) buffering of dialysate, now suggest that dialysis-induced hypotension may be minimized or prevented under certain conditions. Keshaviah and Shapiro examine eight variables (their Table 1) which could account for a fall in blood pressure during or after dialysis and state that its genesis is . . complex, controversial, and multifactorial. With laudable caution, Keshaviah and Shapiro decline to indict a single causative mechanism though they conclude that at low dialysate sodium concentrations acetate . . is associated with a more marked fall of blood pressure than is bicarbonate. Heneghan accepts the evidence tying acetate to hypotension and explores the question of Why is acetate associated with greater morbidity during dialysis? In a simple but telling double-blind experiment, Heneghan administered oxygen or compressed air to five patients during 30 hemodialyses to test his thesis that acetate-caused hypoxemia was responsible for hypotension. In this study, when hypoxemia was prevented by oxygen, hypotension was avoided and dialysis was better tolerated. According to Heneghan, acetate metabolism reduces CO2 production which in turn induces hypoventilation and hypoxemia. Recognizing that long term comparisons of acetate and bicarbonate have not been done, Heneghan nevertheless concludes that . . acetate must be considered suspect. Directors of dialysis units must weigh the data for themselves to determme whether or not to invest in machines equipped to infuse bicarbonate as the principal dialysate buffer. In my view, the case is still open. Adding another pump increases the probability of mechanical error. Until the controlled studies called for by both essayists are performed, nearly all patients prone to hypotension can be managed by using a normal or high dialysate sodium concentration combined with administration of nasal oxygen throughout dialysis.

The Effect of Dialysate Sodium Concentration on Body Fluid Compartment Volume, Plasma Renin Activity and Plasma Aldosterone Concentration in Chronic Hemodialysis Patients

Six stable chronic hemodialysis patients received six hemodialysis treatments: two each with the dialysate sodium concentration (DNa) 7% greater than serum sodium concentration, two with a DNa equal to serum sodium concentration and two with the DNa 7% less than the serum sodium concentration. During one treatment with each dialysate 2 kg of fluid was removed and during the other treatments the patient's weight was kept constant. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), plasma volume (PV), plasma renin activity (PRA), aldosterone (ALDO), Na, BUN and osmolality were determined before and after each treatment. Fluid removal during dialysis had no effect on ICW with essentially all the fluid removed during dialysis coming from ECW. ICW increased with low DNa and decreased with high DNa. The effect of DNa on ECW and PV was the opposite of that on ICW. PRA increased and ALDO decreased during dialysis. Predialysis ALDO directly correlated with PRA (r = 0.68, p less than 0.001) but not with serum potassium concentration. Post dialysis ALDO was not significantly correlated with either PRA or potassium. Fluid removal and low DNa increased both PRA and ALDO. These studies indicate that water shifts from the extracellular space into intracellular space when DNa is lower than serum Na and the reverse is true when DNa exceeds serum Na. Plasma aldosterone decreases during dialysis despite an increase in PRA, possibly related to the decrease in serum potassium concentration. The effect of fluid removal and low DNa on PRA and ALDO may be related to a reduction in ECW and/or PV.