The Neglect of Sodium Restriction in Dialysis Patients: A Short Review

In end-stage renal failure, natriuresis decreases, sodium accumulates, and extracellular volume (ECV) excess develops. In 1962, Scribner, reporting about the first maintenance hemodialysis (HD) patient, observed that ECV control using a low-salt diet and ultrafiltration led to blood pressure (BP) normalization. Thus, the concept of dry weight, the ideal postdialysis weight allowing for a stable normal BP, was born. Achieving dry weight requires a combination of negative diffusive sodium balance, adequate ultrafiltration, and a low-salt diet. Unfortunately, the low-salt diet is very often neglected today. In the late 1960s, BP control was achieved in 90% of HD patients using low-sodium dialysis and a low-salt diet. As time passed and HD duration was reduced, there was a worsening BP control and subsequent increasing in morbidity and mortality.
In recent years, interventional studies have examined the effects of reducing sodium in dialysate, in diet, or in both. All of them show that low-salt diet is essential for BP control in HD. While the healthy population is advised to eat a reasonably low-salt diet (5 g of NaCl), the K/DOQI Guidelines and the European Best Practice Guidelines surprisingly do not even mention salt restriction.
To achieve dry weight under the present conditions, with short HD duration and a frail population, it is mandatory to reduce the interdialytic weight gain. A low-salt diet is, more than ever, a necessity.     

Length of Dialysis Session Is More Important Than Large Kt/V in Hemodialysis

Long, slow hemodialysis (3 × 8 hours/week) has been used without significant modification in Tassin, France, for 30 years with excellent morbidity and mortality rates. A long dialysis session easily provides high Kt/V_urea and allows for good control of nutrition and correction of anemia with a limited need for erythropoietin (EPO). Control of serum phosphate and potassium is usually achieved with low-dose medication. The good survival achieved by long hemodialysis sessions is essentially due to lower cardiovascular morbidity and mortality than in short dialysis sessions. This, in turn, is mainly explained by good blood pressure (BP) control without the need for antihypertensive medication. Normotension in this setting is due to the gentle but powerful ultrafiltration provided by the long sessions, associated with a low salt diet and moderate interdialytic weight gains. These allow for adequate control of extracellular volume (dry weight) in most patients without important intradialytic morbidity. Therefore, increasing the length of the dialysis session seems to be the best way of achieving satisfactory long-term clinical results.     

Fluid balance, dry weight, and blood pressure in dialysis

The total amount of sodium present in the body controls the extracellular volume. In advanced renal failure, sodium balance becomes positive and the extracellular volume expands. This leads to hypertension, and vascular changes that lead to adverse cardiovascular consequences in dialysis patients. Controlling the body sodium content and the extracellular volume allows one to better control hypertension and its consequences. This can be achieved by reducing the sodium input (sodium dietary restriction and reasonably low sodium dialysate) and/or by increasing the sodium output (ultrafiltration by convection). The discontinuous nature of hemodialysis causes saw-tooth volume fluctuations. This has led to the concept of dry weight (DW), a crucial component of dialysis adequacy. Assessment and achievement of DW is feasible on pure clinical grounds. But its relative lack of accuracy (and the physicians' progressive lack of interest in bedside examination) has led to several nonclinical methods of assessing DW in an effort to improve the assessment of fluid status in dialysis patients.     

We Should Strive for Optimal Hemodialysis: A Criticism of the Hemodialysis Adequacy Concept

Adequacy of hemodialysis is frequently equated with Kt/V_urea , the amount of urea clearance (K) multiplied by time (t) and divided by urea distribution volume (V). Several formulas have been developed to calculate Kt/V_urea from the pre‐ and post‐dialysis urea concentrations. In three‐times‐weekly hemodialysis, a single pool (spKt/V_urea) value of 1.3 per treatment is commonly considered to indicate adequate therapy.
Despite providing the recommended spKt/V_urea of 1.3 per treatment, short dialysis with rapid ultrafiltration is associated with multiple intradialytic and interdialytic complications. Patients experience cramps, nausea, vomiting, headaches, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control, left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality.
According to Webster's dictionary, "optimal" means most desirable or satisfactory; "adequate" means sufficient for a specific requirement or barely sufficient or satisfactory. Optimal dialysis is the method of dialysis yielding results that cannot be further improved. New approaches, including hemeral quotidian or long nocturnal dialysis, provide opportunities to abandon the notion that adequate dialysis is "good enough" for our patients. Optimal dialysis should be our goal. Dialysis sessions should be long and frequent enough to provide excellent intra‐ and interdialytic tolerance of hemodialysis, normalization of serum calcium and phosphorus, blood pressure control, normal myocardial morphology and function, and hormonal balance, and to eliminate all, even subtle, uremic symptoms.     

Arterial Hypertension Is Associated with Increased Serum Lipoprotein(a) Levels in End‐Stage Renal Disease Patients

In addition to disorders in lipoprotein metabolism, several other factors are involved in the development of atherosclerotic changes in end‐stage renal disease (ESRD) patients. One of these is arterial hypertension. We evaluated serum lipids—total cholesterol (TC), triglycerides (TG), apolipoproteins (A_I , A _II , B, E), lipoprotein(a) [Lp(a)]—in 109 ESRD patients on dialysis [46 on hemodialysis (HD); 63 on continuous ambulatory peritoneal dialysis (CAPD)] and in 45 hyperlipidemic patients without renal failure (HL group). Dialysis patients were divided in two groups. Group A included 42 hypertensive patients (mean age: 62.3 ± 15.5 years) whose blood pressure (BP) was satisfactorily controlled with anti‐hypertensive medications. Group B included 67 non hypertensive patients (mean age: 66.6 ± 11.9 years). Levels of Lp(a) were significantly higher in both the HD (p = 0.001) and the CAPD (p < 0.05) patients as compared with the HL group. When the HD and CAPD groups were divided into hypertensive and non hypertensive patients, Lp(a) levels were significantly higher in the hypertensive patients; this difference was not observed among non renal failure patients. These results indicate that arterial hypertension is associated with elevated Lp(a) serum levels in ESRD patients undergoing either HD or CAPD.     

Residual renal function and arterial stiffness mediated the blood pressure change during interdialytic weight gain in hemodialysis patients

Volume overload is thought to be the main cause of hypertension in dialysis patients. However, the effect of interdialytic weight gain (IDWG) in hemodialysis (HD) patients, which was considered as an increase in extracellular water (ECW), on blood pressure (BP) change, was controversial. Our aim was to examine the changes in hemodynamics and arterial stiffness during IDWG in HD patients and attempt to explore the possible mechanism of diverse BP change. Thirty prevalent patients on HD were enrolled. The height, weight, BP, blood chemistry, volume status assessed by bioelectrical impedance analysis, hemodynamic parameters obtained by echocardiography, and pulse wave velocity (PWV) were collected within 1 hour postdialysis and again just before the next dialysis session. Meanwhile, blood samples were drawn to analyze vasoactive hormones, including renin, angiotensin II, catecholamine, and endothelin. The patients' weights and ECWs during the next predialysis were significantly higher than those during the postdialysis. The BP showed no difference between postdialysis and the next predialysis. There was an obvious increase in cardiac output and decrease in total peripheral resistance as a whole during the next predialysis than that during postdialysis. When patients were divided into the BP increase group (BPI group, 13 patients) and BP decrease group (BPD group, 11 patients) according to the change in systolic BP higher than 10 mmHg, both groups displayed a significant increase in weight, ECW, cardiac output, and a decrease in total peripheral resistance. As compared with the BPI group, patients in the BPD group had significantly lower IDWG, shorter time on dialysis treatment, and higher residual renal function. A decrease in catecholamine and endothelin in the next predialysis was obvious in the BPD group. There was a significant decrease in PWV at the next predialysis in the BPD group while the PWV did not change significantly in the BPI group. Our results showed that the diverse BP change during IDWG was significantly affected by residual renal function, PWV, and vasoactive substances.     

The Clinical Impact of Increasing the Hemodialysis Dose

Good evidence suggests that improvements in dialysis efficiency reduce morbidity and mortality of hemodialysis (HD) patients. Dialysis efficiency has also been related to better control of arterial blood pressure (BP), anemia, and serum phosphorus levels, and to improvement in patients' nutritional status. Over a 2‐year period, the present self‐controlled study of 34 HD patients (23 men, 11 women; age, 52.6 ± 14.5 years; HD duration, 55.9 ± 61.2 months) looked at the effect on clinical and laboratory parameters of increasing the delivered dialysis dose under a strict dry‐weight policy. Dialysis dose was increased without increasing dialysis time and frequency. A statistically significant increase was seen in delivered HD dose: the urea reduction ratio (URR) increased to 60% ± 10% from 52% ± 8%, and then to 71% ± 7% (p < 0.001); Kt/V_urea increased to 1.22 ± 0.28 from 0.93 ± 0.19, and then to 1.55 ± 0.29 (p < 0.001). A statistically significant increase in hemoglobin concentration also occurred—to 10.8 ± 1.9 g/dL from 10.4 ± 1.7 g/dL, and then to 11.0 ± 1.3 g/dL (p < 0.05 as compared to baseline)—with no significant difference in weekly erythropoietin dose. Statistically significant decreases occurred in the systolic and diastolic blood pressures during the first year; they then remained unchanged. Systolic blood pressure decreased to 131 ± 23 mmHg from 147 ± 24 mmHg (p < 0.001); diastolic blood pressure decreased to 65 ± 11 mmHg from 73 ± 12 mmHg (p < 0.001). Serum albumin increased insignificantly to 4.4 ± 0.4 g/dL from 4.3 ± 0.4 g/dL, and then significantly to 4.6 ± 0.3 g/dL (p = 0.002 as compared to both previous values). Normalized protein catabolic rate increased significantly to 1.16 ± 0.15 g/kg/day from 0.93 ± 0.16 g/kg/ day (p < 0.001), and then to 1.20 ± 0.17 g/kg/day (p < 0.001 as compared to baseline). We conclude that the increases achieved in average Kt/V_urea per hemodialysis session by increasing dialyzer membrane area, and blood and dialysate flows, without increasing dialysis time above 4 hours, in patients hemodialyzed thrice weekly, coupled with strict dry‐weight policy, resulted in improvements in hypertension, nutritional status, and anemia.     

The pivotal role of sodium balance in control of blood pressure in dialysis patients

In hemodialysis patients, as in patients with normal kidney function, sodium balance is the major determinant of changes in extracellular volume, and extracellular volume is an important determinant of blood pressure. The osmotic thresholds for thirst and ADH release are normal in kidney failure; pre‐dialysis serum sodium concentration shows a high index of individuality in oliguric hemodialysis patients. Non‐osmotic storage of sodium in vascular walls may also amplify the volume‐sensitivity of blood pressure. The variable relationship between volume removal and change in blood pressure described in clinical studies reflects a state of permanent volume expansion in those whose blood pressure does not fall, or rises, during dialysis, whereas those whose blood pressure falls during dialysis are those who approach normovolemia. Rigorous control of extracellular volume often results in perfect blood pressure control, but may be difficult to achieve safely other than with long, slow dialysis combined with dietary salt restriction.     

The International Quotidian Hemodialysis Registry: rationale and challenges

Outcomes from conventional thrice-weekly hemodialysis (CHD) are disappointing for a life-saving therapy. The results of the HEMO Study show that the recommended minimum dose (Kt/V) for adequacy is also the optimum attainable with CHD. Interest is therefore turning to alternative therapies exploring the effects of increased frequency and time of hemodialysis (HD) treatment. The National Institutes of Health have sponsored 2 randomized prospective trials comparing short hours daily in-center HD and long hours slow nightly home HD with CHD. An International Registry has also been created to capture observational data on patients receiving short hours daily in-center HD, long hours slow nightly home HD, and other alternative therapies. Participation by individual centers, other registries and the major dialysis chains is growing and currently data from nearly 3000 patients have been collected. Pitfalls in data collection have been identified and are being corrected. A matched cohort (patients in other registries) study is planned to obtain information regarding hard outcomes expected from these therapies. The Registry may become the most important source of information required by governments, providers, and the nephrological community in assessing the utility of such therapies.     

The ideal home hemodialysis machine

Daily home hemodialysis (HD) patients have a much superior survival rate than patients on regular, 3 times a week in-center HD or on peritoneal dialysis. Present-day HD machines are unsuitable for use at home by patients. We present our concept of the ideal home HD machine that allows daily short and long HD, does all the work preparing for and cleaning up after dialysis, has an intravenous infusion system controlled by the patient, needs no systemic anticoagulation, and teaches and interacts with the patient during dialysis. To fulfill these functionalities, the dialyzer and blood tubing must be integrated with the machine and replaced less often than monthly, the machine must be capable of at least 200 L/week of hemodiafiltration, prepare all fluids necessary between and during dialyses, and all the components and fluids must be much beyond ultrapure.     

Does hemodiafiltration improve the removal of homocysteine?

High prevalence of hyperhomocysteinemia is common in hemodialysis (HD) patients and could contribute to worsen the cardiovascular risk. Beyond vitamin B status, dialysis modality itself could influence homocysteine (Hcy) levels. The objective was compare the reduction rate (RR) of Hcy and cysteine in stable dialyzed patients treated by standard HD or hemodiafiltration (HDF). Seventy‐five patients undergoing stable dialysis through standard high‐flux HD (n = 35) or HDF (n = 40) were included. Biological parameters were determined before and after a midweek dialysis session. Urea percent reduction per session and Kt/V index (K, body urea clearance, T, time of dialysis, and V, urea distribution volume), defined as a marker of dialysis efficacy, were similar between HD and HDF groups. By contrast, higher RR of beta2 microglobulin (β2m) was observed in HDF compared with HD (78.6 vs. 72.0%, respectively; P < 0.001). Likewise, higher RR of Hcy was obtained with HDF compared to HD (46.0 vs. 41.5%, respectively; P < 0.05), whereas the RR of cysteine was similar in both groups. Interestingly, a positive correlation between Hcy RR and urea Kt/V index was observed (r = 0.29, P < 0.05) and between Hcy RR and β2m RR (r = 0.45, P < 0.001). Time‐averaged concentration (TAC) of Hcy was lower with HDF compared with HD (17.8 vs. 19.1 μmol/L, respectively), although not significant. There was no difference in median Hcy according to dialysis modality for neither pre‐ nor postdialysis levels. Significant higher removal of Hcy was observed with HDF compared with standard HD, although urea Kt/V index was similar. Enhanced removal of middle molecules, such as β2m, could be involved in Hcy RR improvement with HDF.     

Management of hypertension in hemodialysis patients

The relationship of hypertension with adverse outcomes is uncertain in the hemodialysis population. If hypertension is an etiologically significant cardiovascular risk factor in hemodialysis patients, the first step would be to assess the level of BP accurately. BP obtained at home over a week and averaged using a validated oscillometric automatic device can prove valuable. To the extent BP lowering influences cardiovascular outcomes, home BP of 150/90 mm Hg would warrant therapy, since it correlates with target organ damage and hypertension diagnosed by ambulatory BP monitoring. To manage hypertension, limiting dietary sodium intake and individualizing dialysate sodium delivery would be first steps. The magnitude of reduction in BP with dietary sodium restriction and the whether dialysate sodium can be safely limited in those who are hypotension-prone is unclear. Antihypertensive drug therapies can effectively reduce BP and are needed by the vast majority of hemodialysis patients. Whether control of hypertension translates into better outcomes is not known, but collective evidence suggests that hypertension should be controlled in hemodialysis patients.     

Cardiovasoactive Peptides in Hemodialysis Patients: Diagnostic Tools and Predictors of Outcome: A Review of Present Knowledge and Future Directions

The main cardiovasoactive peptides involved in cardiovascular adaptation to renal failure and dialysis are reviewed with a special focus on their possible role in pathophysiology, diagnosis of cardiovascular and fluid volume abnormalities, and prognostic information.
The role of vasoactive peptides in cardiovascular stability during hemodialysis (HD) are best seen in sequential HD, where the release of vasoconstrictors is stimulated by volume reduction during ultrafiltration, but is blunted during isovolemic HD, whereas plasma vasodilators increase.
Plasma levels of the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are elevated in fluid volume overload and heart failure and decrease during dialysis. Neuropeptide Y (NPY) is elevated in severe volume overload and hypertension and calcitonin gene-related peptide in large-volume overload. Plasma BNP increases with left ventricular failure and improves during dialysis.
Activation of the sympathetic nervous system as reflected by increased plasma levels of NPY is associated with poor prognosis. High levels of the natriuretic peptides ANP and BNP are likewise predictors of poor prognosis.
Determinations of plasma levels of cardiovasoactive peptides may be helpful in clinical practice to diagnose volume overload and heart failure and to assess the severity of heart failure and of hypertension, as a guide to the choice of dialysis treatment and pharmacotherapy and to monitor treatment. Clinical studies will be needed in HD patients to establish the value of measurement of plasma cardiovasoactive peptides in clinical practice.
The research in this field is still in its infancy and promises to be exciting in the future. There appears to be a balance of vasomotor tone and cardiac response to meet any emergency and stress such as intermittent dialysis. Further knowledge will increase our chances for major therapeutic interventions.     

Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis

Pulmonary hypertension (PH) has been reported in hemodialysis (HD) patients, but data regarding its incidence and mechanisms are scarce. The aims of this study was to evaluate the prevalence of unexplained PH in long-term HD patients, and to examine some possible etiologic factors for its occurrence. The prevalence of PH was estimated by Doppler echocardiography in a cohort of 86 stable patients on HD via arteriovenous access for more than 12 months. All the patients underwent full clinical evaluation, chest radiography, and a standard 12-lead echocardiograph. Laboratory investigation included a mean of 12 months (serum calcium, phosphorus, parathormone (PTH), alkaline phosphatase, lipids, and hemoglobin). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35 mmHg as determined by Doppler echocardiography using the modified Bernoulli equation. Pulmonary hypertension was detected in 23 patients (26.74%). Of those with PH, left ventricular hypertrophy was seen in 13 patients (56.52%), and valvular calcifications in 6 patients (26.08%). There were no significant differences between both groups with regard to age, sex, duration of dialysis, shunt location, and all the biological parameters of the study. The presence of PH was not related to the level of PTH, or the severity of other metabolic abnormalities. This study demonstrates a high prevalence of PH among patients with ESRD receiving long-term HD via surgical arteriovenous access. The role of the vascular access, anemia, or secondary hyperparathyroidism as the etiology of PH in HD patients did not hold in this study.     

Does Blood Pressure Control by Gentle Ultrafiltration Improve Survival in Hemodialysis Patients?

Agentle ultrafiltration can be achieved using a long and slow hemodialysis. It is easier to achieve gentle ultrafiltration if the interdialytic weight intake is moderate ( i.e., if the patient maintains a low sodium diet) and if diffusion allows for a negative or nil sodium balance during the session ( i.e., dialysate sodium < 140 mmol/L). A gentle ultrafiltration allows control of blood pressure by reducing the extracellular volume to its ideal level, the “dry weight,” at the end of the session. Controlling blood pressure reduces cardiovascular mortality, which is by far the foremost cause of death in hemodialysis. Controlling blood pressure means reducing the occurrence of both hypertension and hypotension. Hypotension has been reported to correlate with mortality in hemodialysis as much as or more than hypertension itself. This “U‐curve” phenomenon is not paradoxical. It displays two distinct facts on the same figure: an increased early mortality in hypotensive patients (hypotension is a marker of frailty or congestive heart failure, both of which cause increased mortality) and, on the other hand, the well‐established, long‐term increased mortality in hypertensive patients. Hypotension is not a mandate to undertreat hypertension.     

Interdialytic blood pressure obtained by ambulatory blood pressure measurement and left ventricular structure in hypertensive hemodialysis patients

Unlike in subjects with normal renal function, the relationship between hypertension and cardiovascular morbidity and mortality in dialysis patients is still being debated. In order to clarify this issue, we performed 44-hour ambulatory blood pressure measurements (ABPM) during the interdialytic period in a group of 164 hypertensive patients, the blood pressure (BP) control based on conventional antihypertensive strategy previously, on chronic hemodialysis treatment in the Mediterranean region of Turkey. These results were then compared with their echocardiographic data. This is a cross-sectional analysis. The mean ABPM during 44 hours was close to the manually measured predialysis value, but there was a gradual increase in the ABPM values in the interdialytic period. When divided into a group with mild or no left ventricular hypertrophy (LVH) (45 patients) and severe LVH (119 patients), the latter had significantly higher BP levels in all separate periods, while the difference in predialysis BP was not significant. Patients with severe LVH had larger left atrium and left ventricular diameters, and consumed more antihypertensive drugs. Systolic BP during the night before dialysis showed the strongest relation to LVH, but interdialytic weight gain was also independently related to LVH. Yet, 56% of the patients with systolic BP <135 had severe LVH. There is not only an association between BP and presence of LVH, but it is shown that volume expansion is also an important independent determinant of LVH. This may explain the difficulty in identifying hypertension as a cardiac risk factor in these patients.     

The carbon footprints of home and in‐center maintenance hemodialysis in the United Kingdom

Climate change presents a global health threat. However, the provision of healthcare, including dialysis, is associated with greenhouse gas emissions. The aim of this study was to determine the carbon footprints of the differing modalities and treatment regimes used to deliver maintenance hemodialysis (HD), in order to inform carbon reduction strategies at the level of both individual treatments and HD programs. This was a component analysis study adhering to PAS2050. Emissions factors were applied to data that were collected for building energy use, travel and procurement. Thrice weekly in‐center HD has a carbon footprint of 3.8 ton CO₂ Eq per patient per year. The majority of emissions arise within the medical equipment (37%), energy use (21%), and patient travel (20%) sectors. The carbon footprint of providing home HD varies with the regime. For standard machines: 4 times weekly (4 days, 4.5 hours), 4.3 ton CO₂ Eq; 5 times weekly (5 days, 4 hours), 5.1 ton CO₂ Eq; short daily (6 days, 2 hours), 5.2 ton CO₂ Eq; nocturnal (3 nightly, 7 hours), 3.9 ton CO₂ Eq; and nocturnal (6 nightly, 7 hours), 7.2 ton CO₂ Eq. For NxStage equipment: short daily (5.5 days, 3 hours), 1.8 t CO₂ Eq; 6 nightly nocturnal (2.1 ton CO₂ Eq). The carbon footprint of HD is influenced more by the frequency of treatments than by their duration. The anticipated rise in the prevalence of home HD patients, dialyzing more frequently and for longer than in‐center patients, will increase the emissions associated with HD programs (despite reductions in patient travel emissions). Emerging technologies, such as NxStage, might offer a solution to this problem.