Description of the condition
Kidneys perform a vital role in controlling salt and water balance. People with end-stage kidney disease who are receiving maintenance haemodialysis rely on therapy to optimise salt and water levels. The current average concentration of salt (sodium) in dialysis fluid (dialysate) globally is 140 mM (Hecking 2011; Mc Causland 2012; Peixoto 2011), which is relatively high compared with concentrations used in the 1970s and 1980s. The use of higher sodium dialysate concentrations has been influenced by a desire to make dialysis more comfortable for patients, who often experience cramps and symptomatic drops in blood pressure (BP) (intradialytic hypotension) (Cybulsky 1985; Port 1973; Stewart 1972; Wilkinson 1977). Dialysate sodium concentrations that are higher than patients' blood sodium levels facilitate fluid removal during dialysis (ultrafiltration) and improve the likelihood of maintaining normal BP and heart function during dialysis. However, higher sodium levels mean that people on haemodialysis are often dialysing with a positive sodium gradient between their blood and the dialysate (Munoz Mendoza 2011; Peixoto 2011; Raimann 2009). By dialysis session end, patients often gain sodium, which increases thirst, fluid gain (interdialytic weight gain), and BP (hypertension). Consequently, most people on typical in-centre haemodialysis schedules, of four hours three times weekly, have chronic salt and water overload. Despite antihypertensive medications, hypertension is not controlled adequately (Agarwal 2003; Rahman 1999; Zazgornik 1997). Elevated BP and salt and water overload are recognised as key contributors to high levels of heart-related illness and cardiovascular deaths among people on dialysis (Charra 2004). Lower dialysate sodium concentrations may improve survival by ameliorating salt and water overload.
Sodium loading during haemodialysis is thought to account for a significant proportion of salt and water overload problems, and may occur in a number of ways: higher concentrations of sodium in dialysate, sodium profiling programs, saline used to treat intradialytic hypotension and to prime or wash-back the extracorporeal blood circuit.
Excessive body sodium content is thought to account for why people receiving maintenance haemodialysis have ongoing problems with excess thirst, fluid overload and high interdialytic weight gains (Davenport 2008; Fischbach 1988; Kimura 1984; Matsuoka 1990; Shepherd 1987; Stiller 2001; Van Stone 1982). In turn, these issues can lead to hypertension, left ventricular hypertrophy, congestive heart failure and ultimately, premature death (Charra 2004). Moreover, elevation in serum sodium concentration (above 135 mM) has been observed to directly increase BP by stiffening blood vessel walls (Oberleithner 2007).
Description of the intervention
Dialysate sodium concentration is considered to be low when a negative concentration gradient exists between the dialysate and the patient's bloodstream. Many studies do not measure patients’ actual serum sodium or calculate the gradient. For this review, we will consider dialysate sodium levels below 138 mM to be low; 138 mM to 140 mM as neutral; and more than 140 mM as high.
How the intervention might work
Haemodialysis removes fluid and solutes through convection and diffusion. Convective losses of sodium during haemodialysis are dependent on ultrafiltration. Diffusive transfer of sodium depends on the direction of the sodium gradient between the dialysate and the patient's plasma. Plasma contains negatively charged proteins that may complex with sodium ions, reducing their availability to move across the dialyser membrane. Dialysate contains no proteins, therefore all ionised sodium is able to move across the membrane. This difference in available diffusible sodium is known as the Gibbs-Donan effect (Locatelli 1984). Dialysate sodium concentration is estimated from dialysate conductivity multiplied by 10 (Gotch 1990; Ragon 1985). Sodium gradient can be considered neutral if the dialysate sodium concentration is set around 2 mM below the plasma sodium concentration (Flanigan 2008; Lomonte 2011).
The sodium gradient becomes negative if dialysate sodium concentration levels are reduced below equivalence. Negative sodium gradient between the patient's blood and the dialysate induces diffusive sodium loss during that dialysis session. Desalination may lead to less thirst and lower interdialytic weight gains, which may lead to less extracellular fluid overload, reduced hypertension, and ultimately, reduced left ventricular hypertrophy and cardiovascular mortality.
However, when a negative sodium gradient exists osmotic drag for refilling the vascular space during ultrafiltration is reduced, which may cause haemodynamic instability and more episodes of intradialytic hypotension (Peixoto 2011; Santos 2008), especially when large ultrafiltration rates/volumes are required. Repeated intradialytic hypotension episodes are associated with temporary or permanent loss of heart contractility and congestive heart failure (Boon 2004; Bos 2000; McIntyre 2008; McIntyre 2014).
Why it is important to do this review
Recent observational data have signalled a possible association between lower dialysate sodium concentrations and higher mortality rates (Hecking 2012; Mc Causland 2012). Low dialysate sodium concentration may make dialysis uncomfortable, and patients dialysed with low sodium concentrations may experience sudden intradialytic hypotension, leading to temporary or permanent reductions in heart contractility (Boon 2004; Bos 2000; McIntyre 2008).
Whether chronic haemodialysis users are more at risk from complications of low or high sodium dialysate concentration may depend on their comorbidities. Clarification is needed about which competing risks are more important and relevant to achieving positive patient outcomes. This review will enable informed choices to be made about optimum dialysate sodium concentrations for both haemodialysis consumers and facilities providing haemodialysis.