**3.1 Salt and fluid balance: Osmometric thirst and the sodium 'set-point'**

The patient's hydration status during the interdialytic period depends on both the weight achieved after dialysis and the fluid gained by the patient before the next session. Very high IDFG can make it impossible for the patient to remain close to normal hydration and to control pre-dialysis blood pressure. Another problem, particularly in elderly and malnourished patients, is the inability to tolerate the ultrafiltration rates required to remove a moderate volume of accumulated fluid. Whether the patient is gaining excessive volumes or failing to transfer fluid from the tissues into the circulation sufficiently rapidly, the solution is to try and reduce their IDFG.

A typical haemodialysis patient in the UK accumulates about 2 litres of excess fluid in the intervals between sessions. When they attend for dialysis the machine is programmed to remove the excess fluid by ultrafiltration. Every litre removed in this way will carry with it about 137 mmol of sodium ions, though the actual amount will depend on the serum sodium level at the time the fluid was removed. As 137 mmol is the amount of sodium in 8 g of salt, the typical UK patient loses sodium equivalent to about 16 g of salt at each dialysis session. The body does have 'non-osmotic' sodium stores in tissues such as the skin and connective tissues (Titze, 2008) and it is possible that sodium can be recruited into or removed from these stores to buffer short term fluctuations in serum sodium. However, if the patient is assumed to be in steady state on the timescale of the interdialytic period, they must be making up for the sodium lost by taking in the equivalent of 16 g of salt between sessions. Sodium does come in other forms other than salt, such as sodium bicarbonate, but it is usually combined with chloride.

If retained in the body, the salt taken in will cause 'osmometric' thirst. Osmometric thirst is triggered when increased osmolarity of the extracellular fluid causes osmoreceptor cells in the hypothalamus to shrink. Volumetric thirst, which occurs when the body loses both water and salt, is triggered when baroreceptors in the atria sense low cardiac return volume. Haemodialysis patients may experience volumetric thirst immediately after dialysis if they are dehydrated, but at other times their thirst is primarily osmometric. Fluid drunk in response to post-dialysis dehydration does not usually lead to increased IDFG as it simply delays osmometric thirst until the patient has consumed enough salt. An important exception to this occurs if a patient with good residual renal function is dehydrated, as they will need to take in enough fluid to normalise their hydration before diuresis starts.

Osmometric thirst is part of the body's system for maintaining electrolyte balance. If our typical haemodialysis patient is anuric (unable to lose sodium via the kidneys), they will need to take in about one litre of water to dilute every 8g salt consumed to a normal

Management of Fluid Status in

**3.2 Minimising sodium loading during dialysis** 

Haemodialysis Patients: The Roles of Technology and Dietary Advice 193

During dialysis, sodium diffuses between the dialysate and the plasma water across the dialyser membrane until equilibrium is achieved. The plasma contains negatively charged proteins that are too large to pass through the dialyser membrane. This leads to retention of positively charged ions like sodium in the plasma water to maintain electric neutrality. This trapping of positively charged ions by negatively charged proteins leads to a higher concentration of sodium in the plasma water than in the dialysate at equilibrium (this is called the Gibbs-Donnan effect). Most labs measure the sodium concentration in the total plasma (the serum sodium), rather than the plasma water. Electrolytes in the total plasma are diluted by about 6% because of the volume taken up by the proteins and lipids. In most patients, this dilution more-or-less cancels out the Gibbs Donnan effect so that the measured

Through the plasma water, the sodium level in the patient's extracellular water equilibrates with the dialysate sodium during dialysis. Patients treated with dialysate sodium that is higher than their pre-dialysis serum level will receive an infusion of sodium during dialysis. Consider an anuric 70 kg male patient whose set point leads him to come for dialysis with a serum sodium of around 137 mmol/l. If he is treated with dialysate sodium of 140 mmol/l, there will be a net transfer of between 45 and 100 mmol of sodium from the dialysate to the patient during the session. The actual amount will depend on the movement of water out of the intracellular space to achieve osmotic equilibrium and transfers of other solutes. Although this sodium transfer is much smaller than the typical loss through ultrafiltration (about 275 mmol for 2 litres removed), reducing the dialysate sodium by 3 mmol/l should

To eliminate unnecessary intradialytic sodium loading, and avoid the associated fluid gain, individualisation of the dialysate sodium based on the patient's pre-dialysis serum or plasma water sodium level has been recommended (de Paula et al, 2004; Santos & Peixoto, 2008). A simpler approach, which will achieve similar benefits in terms of reduced IDFG and blood pressure control, is to standardise the dialysate sodium levels towards the lower end of the normal range. Patients who normally have high serum sodium levels may experience osmotic disequilibrium (headache, nausea and hypertension) if treated with dialysate sodium of 135-137 mmol/l, but many will have no symptoms. Patients who have very low pre-dialysis sodium levels will gain sodium during dialysis, but this will not necessarily increase IDFG if their fluid intake is not controlled by osmometric thirst. Resetting of the sodium set-point, or 'osmostat', to very low levels has been reported (for example, as a complication of spinal cord injury) but it is rare and would lead to unbearable

Control of interdialytic fluid gains is important both in the maintenance of near-normal hydration and the minimisation of intradialytic hypotension and discomfort. Patients who consume less than 6 g of salt per day should accumulate no more than 0.8 l of fluid per day (it takes 750 ml of water to dilute 6 g salt to 137 mmol/l). Most patients are able to tolerate the ultrafiltration rates required to remove this amount of fluid. Smaller patients and those with impaired autonomic function may need a tighter salt restriction, especially when they

Unlike most of the dietary restrictions placed on dialysis patients, the recommendation to limit salt intake applies to the whole population, including healthcare professionals! The World Health Organisation recommends a maximum salt intake of 5 g/day and regularly convenes meetings to discuss reducing salt consumption at population level (WHO, 2010).

serum sodium post-dialysis is usually close to the dialysate sodium level.

lead to a decrease in IDFG of at least 0.3 kg in this patient.

thirst after dialysis with dialysate sodium in the normal range.

**3.3 Recommended salt consumption** 

have three days between dialysis sessions.

physiological level. The patient will consume fluid with their food, when taking medications and in beverages taken socially. They may not even be aware of feeling thirsty, although many haemodialysis patients do find thirst a problem, but if salt consumption gets ahead of fluid intake, osmometric thirst will force the patient to drink enough to restore their serum sodium to an acceptable level. This level varies between patients and has been called the sodium 'set-point' or the 'osmostat' (Keen & Gotch, 2007).

Patients who take in no more fluid than is needed to avoid (or satisfy) salt-induced thirst will present for dialysis with a relatively constant serum sodium. Figure 4 shows predialysis serum sodium averaged over 12 months for 375 haemodialysis patients in the care of the Leeds Teaching Hospitals (Gardiner et al, 2006). The majority of patients appear to have a well defined sodium set point that lies within the normal range of 135 to 145 mmol/l. The patients with relatively high pre-dialysis sodium levels could have a high set-point, but they could also be overriding their thirst to limit fluid gain or be unable to drink freely.

Fig. 4. Pre-dialysis serum sodium level for 375 HD patients. Each bar represents the distribution (mean and standard deviation) of 6 monthly measurements in a single patient.

Low pre-dialysis serum sodium may be due to urinary losses, but this will normally be associated with low IDFG. In patients with low sodium and high IDFG, elevated blood sugar may be responsible. In the group shown in Figure 4, the 28 poorly controlled diabetics (glycosylated haemoglobin >7%) had lower serum sodium (136 vs. 137 mmol/l, p=0.03) and higher fluid gain (2.3 vs. 1.7 kg, p=0.01) compared to well controlled diabetics and nondiabetics. However, the lowest pre-dialysis sodium levels occurred in non-diabetic patients with relatively high IDFG. These patients are taking in excess free water for various reasons including xerostomia (dry mouth, often due to medications), and comfort or social drinking. While patients with high IDFG and low pre-dialysis sodium will benefit from dietary salt restriction, other factors leading to fluid intake should be investigated and resolved if possible.

## **3.2 Minimising sodium loading during dialysis**

192 Technical Problems in Patients on Hemodialysis

physiological level. The patient will consume fluid with their food, when taking medications and in beverages taken socially. They may not even be aware of feeling thirsty, although many haemodialysis patients do find thirst a problem, but if salt consumption gets ahead of fluid intake, osmometric thirst will force the patient to drink enough to restore their serum sodium to an acceptable level. This level varies between patients and has been called the

Patients who take in no more fluid than is needed to avoid (or satisfy) salt-induced thirst will present for dialysis with a relatively constant serum sodium. Figure 4 shows predialysis serum sodium averaged over 12 months for 375 haemodialysis patients in the care of the Leeds Teaching Hospitals (Gardiner et al, 2006). The majority of patients appear to have a well defined sodium set point that lies within the normal range of 135 to 145 mmol/l. The patients with relatively high pre-dialysis sodium levels could have a high set-point, but they could also be overriding their thirst to limit fluid gain or be unable to drink freely.

Fig. 4. Pre-dialysis serum sodium level for 375 HD patients. Each bar represents the distribution (mean and standard deviation) of 6 monthly measurements in a single patient. Low pre-dialysis serum sodium may be due to urinary losses, but this will normally be associated with low IDFG. In patients with low sodium and high IDFG, elevated blood sugar may be responsible. In the group shown in Figure 4, the 28 poorly controlled diabetics (glycosylated haemoglobin >7%) had lower serum sodium (136 vs. 137 mmol/l, p=0.03) and higher fluid gain (2.3 vs. 1.7 kg, p=0.01) compared to well controlled diabetics and nondiabetics. However, the lowest pre-dialysis sodium levels occurred in non-diabetic patients with relatively high IDFG. These patients are taking in excess free water for various reasons including xerostomia (dry mouth, often due to medications), and comfort or social drinking. While patients with high IDFG and low pre-dialysis sodium will benefit from dietary salt restriction, other factors leading to fluid intake should be investigated and resolved if possible.

sodium 'set-point' or the 'osmostat' (Keen & Gotch, 2007).

During dialysis, sodium diffuses between the dialysate and the plasma water across the dialyser membrane until equilibrium is achieved. The plasma contains negatively charged proteins that are too large to pass through the dialyser membrane. This leads to retention of positively charged ions like sodium in the plasma water to maintain electric neutrality. This trapping of positively charged ions by negatively charged proteins leads to a higher concentration of sodium in the plasma water than in the dialysate at equilibrium (this is called the Gibbs-Donnan effect). Most labs measure the sodium concentration in the total plasma (the serum sodium), rather than the plasma water. Electrolytes in the total plasma are diluted by about 6% because of the volume taken up by the proteins and lipids. In most patients, this dilution more-or-less cancels out the Gibbs Donnan effect so that the measured serum sodium post-dialysis is usually close to the dialysate sodium level.

Through the plasma water, the sodium level in the patient's extracellular water equilibrates with the dialysate sodium during dialysis. Patients treated with dialysate sodium that is higher than their pre-dialysis serum level will receive an infusion of sodium during dialysis. Consider an anuric 70 kg male patient whose set point leads him to come for dialysis with a serum sodium of around 137 mmol/l. If he is treated with dialysate sodium of 140 mmol/l, there will be a net transfer of between 45 and 100 mmol of sodium from the dialysate to the patient during the session. The actual amount will depend on the movement of water out of the intracellular space to achieve osmotic equilibrium and transfers of other solutes. Although this sodium transfer is much smaller than the typical loss through ultrafiltration (about 275 mmol for 2 litres removed), reducing the dialysate sodium by 3 mmol/l should lead to a decrease in IDFG of at least 0.3 kg in this patient.

To eliminate unnecessary intradialytic sodium loading, and avoid the associated fluid gain, individualisation of the dialysate sodium based on the patient's pre-dialysis serum or plasma water sodium level has been recommended (de Paula et al, 2004; Santos & Peixoto, 2008). A simpler approach, which will achieve similar benefits in terms of reduced IDFG and blood pressure control, is to standardise the dialysate sodium levels towards the lower end of the normal range. Patients who normally have high serum sodium levels may experience osmotic disequilibrium (headache, nausea and hypertension) if treated with dialysate sodium of 135-137 mmol/l, but many will have no symptoms. Patients who have very low pre-dialysis sodium levels will gain sodium during dialysis, but this will not necessarily increase IDFG if their fluid intake is not controlled by osmometric thirst. Resetting of the sodium set-point, or 'osmostat', to very low levels has been reported (for example, as a complication of spinal cord injury) but it is rare and would lead to unbearable thirst after dialysis with dialysate sodium in the normal range.

### **3.3 Recommended salt consumption**

Control of interdialytic fluid gains is important both in the maintenance of near-normal hydration and the minimisation of intradialytic hypotension and discomfort. Patients who consume less than 6 g of salt per day should accumulate no more than 0.8 l of fluid per day (it takes 750 ml of water to dilute 6 g salt to 137 mmol/l). Most patients are able to tolerate the ultrafiltration rates required to remove this amount of fluid. Smaller patients and those with impaired autonomic function may need a tighter salt restriction, especially when they have three days between dialysis sessions.

Unlike most of the dietary restrictions placed on dialysis patients, the recommendation to limit salt intake applies to the whole population, including healthcare professionals! The World Health Organisation recommends a maximum salt intake of 5 g/day and regularly convenes meetings to discuss reducing salt consumption at population level (WHO, 2010).

Management of Fluid Status in

by a renal dietitian.

Haemodialysis Patients: The Roles of Technology and Dietary Advice 195

The importance of salt restriction for the whole population means that advice on lowering salt intake and recipes for low salt meals are widely available on the internet. The only modification required in dialysis patients is the need to be very careful of salt substitutes as they often contain potassium. Unfortunately the potassium content of processed food is often not clearly labelled. Figure 5 shows the tips for lowering salt intake from the 'Dietary Approaches to Stop Hypertension' brochure (US NHBLI, 2006) adapted for dialysis patients

Patients who can tolerate only very limited fluid removal, and those who are hypertensive in the absence of fluid overload, may need to take further steps to reduce their salt consumption. This will include switching to unsalted butter and bread. If salt-free bread is not available, ways to substitute unsalted rice or pasta for bread should be sought. As these more stringent restrictions are difficult to implement, it is essential to prevent sodium loading during dialysis in these patients. Consideration should be given to lowering the dialysate sodium to 133-135 mmol/l and minimising infusion of normal saline (which

Dialysis patients may have impaired taste sensitivity (Middleton 1999). If salt restriction leads to weight loss because the patient finds their food unappetising, they should be referred to a dietitian to look into the use of acceptable alternative flavourings. The need to check for weight loss and provide individual dietetic counselling is especially important in

There is a sound physiological basis for restricting intake of salt rather than fluids to control IDFG in most patients, though there are few published comparisons of the different approaches. Rupp et al compared patients on a traditional sodium and fluid restricted diet with those given a diet that just restricted sodium and found a significant decrease in IDFG only in the group on the simpler low-sodium diet (Rupp et al, 1978). Kayikcioglu et al compared cardiac function and blood pressure control in two units, one of which practiced a salt restriction strategy while the other relied on the use of anti-hypertensives (Kayikcioglu et al, 2009). The use of salt restriction not only reduced the requirement for antihypertensive medication (7% vs. 42%), but led to significantly lower IDFG (2.29 vs. 3.31 kg) and fewer

With such clear benefits, it is surprising that there is not more emphasis on salt restriction in haemodialysis units. Patient information currently available via the internet tends to focus on fluid restriction, with advice such as using smaller cups, sipping slowly, sucking ice cubes or lemon wedges and keeping a fluid journal. The popularity of fluid restriction may be because fluid intake is relatively easy to monitor, while salt is hidden in manufactured

Dialysis staff can change the focus from fluid to salt restriction and establish a culture of sharing advice for reducing salt intake within the unit. With pressure from the World Health Organisation and national food safety bodies, we should see more low-salt products and increased disclosure of salt content. Tables of salt content in foods that can be used in educational material and quizzes are available from organisations such as the US Department of Agriculture (USDA, n.d.) and the Australian Healthy Eating Club (Healthy Eating Club, n.d.). Staff aiming to reduce their own salt intake to < 6 g/day will be able to swap tips rather than impose rules. How long does it take to get used to unsalted butter? Which breakfast cereals have the lowest salt content? How easy is it to make low salt bread? Haemodialysis patients with little or no residual renal function can get feedback on the impact of any dietary modification simply by monitoring their fluid gains. As a rough

foods and cutting out the 'visible' added salt has a disappointing impact on IDFG.

contains 154 mmol/l sodium) at the end of dialysis (Penne et al, 2010).

patients who need a very restricted salt intake as described above.

**3.5 Implementing salt restriction: Staff education** 

episodes of intradialytic hypotension (11% vs. 27%).

The USA, Canada, UK, Australia and New Zealand are among the countries that consider a recommended daily allowance (RDA) of 6 g/day to be achievable and sustainable. A salt intake of 6 g/day is equivalent to a sodium intake of 2.3 g/day or 100 mmol/day.

The RDA for patients with kidney failure, as with all patients at high risk of cardiovascular disease, should probably be lower than for the general population. However, the practical and psychological benefit of having the same dietary restriction as family and carers, as well as the risk of malnutrition due to an unappetising diet, makes the national RDA a more realistic target for most patients.
