Reduction of dietary sodium intake
The rationale supporting dietary Na restriction in patients with ESKD is that they are primarily drinking in response to osmometric thirst, due to activation of osmoreceptor cells in the hypothalamus caused by increased extracellular fluid osmolality.
The benefits of a low-salt diet in patients with ESKD have been well demonstrated in adult studies [
40‐
42]. Among them, a post-hoc analysis of 1770 patients in the hemodialysis study found that higher reported dietary sodium intake was independently associated with greater ultrafiltration requirements and greater all-cause mortality [
40]. Two randomized crossover trials compared an Na-restricted diet versus a free diet in adults with 3–4 CKD: extracellular fluid volume, measured by bioimpedance spectroscopy, significantly decreased with sodium restriction in both studies, together with blood pressure and body weight [
41,
42].
However, the possible detrimental effect of an overly restrictive diet on nutritional status needs to be born in mind.
The average dietary Na intake and its effect on fluid have never been investigated in children on dialysis. As regards predialysis children, data from the CKiD Study showed that the median Na intake in children with CKD 2–4 was 3089 mg/day, exceeding the recommended maximum daily intake for all age groups, in adolescents in particular [
43]. Fast foods were the largest single source of sodium, contributing 9.4% of the total [
44]. These data confirmed that pediatric patients usually enter ESKD without having adapted to salt restriction.
Both the Kidney Dialysis Outcome Initiative (KDOQI) and the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the restriction of Na intake for children with CKD who have hypertension or pre-hypertension, on the basis of the age-based recommended daily intake for healthy children [
45,
46]: upper limits for Na intake are 1500 mg/day for children aged 2–3 years, 1900 mg/day for children aged 4–8 years, 2200 mg/day for children and adolescents aged 9–13 years and 2300 mg/day for the population aged ≥ 14 years.
But how can dietary Na restriction be achieved? Simply asking the parents not to add salt at the table or while cooking is not enough, as this source accounts for less than 15% of total Na intake, while salt added by manufacturers during food processing and Na occurring naturally in foods provide almost 75 and 10% of the total ingested Na, respectively. Continuous dietary counselling from an expert pediatric dietician is therefore mandatory to help children and their families to choose the right foods. The major obstacle to a low-salt diet in children is non-compliance, due to the common perception that low-salt foods are tasteless. When facing this problem, it should be remembered that sodium intake has all the characteristics of a true addiction, as salt sensing of the tongue is strictly dependent on the amount of ingested Na and adaptation of the taste receptors is a long process: only after several months of eating a low-salt diet will salt-rich food be perceived as too salty. Occasional salt-rich food intake hinders this process; therefore, the consumption of Na-rich food during dialysis should be discouraged. A major multidisciplinary effort is needed to help the child and their parents adapt to Na restriction.
Optimization of HD prescription
Dialysate sodium
Sodium removal during dialysis is the sum of convective losses (with ultrafiltration) and diffusive losses, which are dependent on the diffusion gradient between plasma and dialysate. Under the usual dialysate Na prescription of 138–140 mEq/L, more than 80% of Na removal is convective. Reduction of dialysate Na has been proposed as a possible strategy to optimize Na and fluid management.
Some facts should be taken into account when considering this option:
-
Measured dialysate Na is often not equivalent to prescribed dialysate Na and, in particular, a tendency towards higher measured dialysate Na than that prescribed has been reported [
60]
-
The availability of Na for diffusion across the HD membrane is influenced not only by plasma and dialysate Na concentrations, but also by the complexing of Na with other anions, by the Gibbs-Donnan effect and by Na concentration in plasma water, which is different from the total plasma concentration. It has been estimated that Na removal can occur only when dialysate Na is at least 2 mmHg lower than the plasma Na concentration.
-
Lowering dialysate Na could be associated with lower thirst, lower IDWG and better blood pressure control, but a higher incidence of intradialytic events. On the contrary, patients treated with higher dialysate Na can tolerate the HD session better, but often at the price of higher IDWG and increased thirst and blood pressure levels [
60,
61].
-
The use of Na profiles has been proposed to optimize both HD tolerance and fluid control, but this strategy could be associated with high time-averaged Na concentrations, and high Na loading [
60].
In summary, the available evidence does not allow for the identification of a “one size fits all” level of optimal dialysate Na [
61]. In this context, it is not surprising that there is a discrepancy between the “Volume First” proposal put forward in the adult nephrology community, which emphasizes the need for avoiding intradialytic Na loading and suggests a dialysate Na of 134–138 mEq/L, and the position of the DOPPS Group, which suggests not prescribing dialysate Na concentration lower than 138 mEq/L [
39,
62].
The pediatric experience in this field is much more limited. The huge intra- and inter-patient variability of pre-HD plasma Na has been confirmed in pediatric patients and makes the individualization of dialysate Na prescription challenging to implement in clinical practice. In a small pediatric study of 480 HD sessions in 5 children, a reduction of dialysate Na from 140 to 138 mEq/l was associated with lower IDWG and improved pre-HD systolic and diastolic blood pressure (from 133 to 127 and from 84 to 73 mmHg, respectively) [
63].
Taking all these data into account, a reasonable approach could be to prescribe a dialysate Na of 138 mEq/l in most children treated with HD; lower dialysate Na should be considered in the case of severe difficulties in controlling IDWG and fluid excess, while prescription of higher dialysate Na should be restricted to children at high risk of intradialytic events.
Convective therapies
The benefits of convective therapies over standard bicarbonate HD have been investigated by some large randomized controlled trials and meta-analyses in adults, which showed that high-volume on-line hemodiafiltration (HDF), with a convective volume of at least 17–23 l/session in the post-dilution mode, is associated with improved overall survival compared to bicarbonate HD, mainly resulting from reduced cardiovascular mortality [
64]. Different mechanisms have been advocated to explain these findings, including a lower incidence of intradialytic hypotension and better Na management with convective therapies.
Pediatric data comparing HD and HDF are still lacking. Preliminary data from the HDF-Heart-Height (3H) study demonstrated that prevalent pediatric patients treated with HDF were less likely to have fluid overload compared to those treated with bicarbonate HD according to bioimpedance spectroscopy. Although no difference in IDWG was observed, children on HDF required fewer rescue sessions [
65].
Based on the available evidence, until the definitive results of the 3H study are published, high volume online HDF should be considered the dialysis modality of choice in children on extracorporeal dialysis at risk of fluid overload and cardiovascular impairment.
Intensified HD/HDF
In several adult clinical trials, intensified HD or HDF schedules (daily or nocturnal, home or in-centre HD or HDF) have been associated with clear clinical cardiovascular benefits, in particular, a lower need for aggressive ultrafiltration, lower IDWG, reduced intradialytic events and myocardial toxicity, better blood pressure control and reduced LVMI [
66,
67]. Remarkably, a post hoc analysis carried out by the Frequent Hemodialysis Network trial showed that the improvement in left ventricular mass observed in cases of more frequent dialysis was likely caused by extracellular volume reduction directly and not only via an effect on blood pressure [
67].
Some pediatric single-centre studies, which enrolled a total of more than 40 patients, confirmed the beneficial effect of daily and nocturnal HD or HDF on intermediate cardiovascular outcomes, such as blood pressure and LVMI [
68‐
70].
Considering all the available evidence, intensified HD schedules may be considered the best strategy to counteract volume overload in patients with fluid-dependent cardiovascular impairment.