What is the issue?
Kidneys control salt and water balance in the body by the regulation of urine production. When kidneys no longer work, urine production ceases or becomes insufficient and salt and water balance must be managed using dialysis. Doctors looking after haemodialysis patients must select an appropriate amount of sodium to use in the dialysis fluids that are used to wash the patient's blood. If the sodium level in these fluids is too high, this can lead to the patient feeling thirsty after treatment, drinking too much more water and becoming fluid overloaded by the time the next treatment is due, which can cause heart damage. On the other hand, if the sodium level is too low in dialysis fluids, this will cause the patient to have cramps and drops in blood pressure, which is uncomfortable and potentially also a cause heart damage. The "right" sodium level for dialysis fluid is unknown.
What did we do?
We combined all studies of people treated with haemodialysis where outcomes were compared between people receiving low sodium in their dialysis fluid and those receiving higher levels.
What did we find?
We found 12 studies comparing low sodium levels in dialysis fluid with neutral or high sodium levels. Many studies were performed prior to 2000, studying technology and patients that are not always relevant today. Most were short-term studies, only lasting a few weeks. Our main findings in these studies were; that low sodium in dialysis fluid improves blood pressure and reduces gain of salt and water in between dialysis treatments, which are probably good things, but increases the number of cramps and low blood pressure events experienced by patients during dialysis, which are definitely bad things. The studies did not provide enough information about the participating patients for us to know which patients might benefit from low sodium dialysis fluid, and which patients might instead be harmed. The studies did not provide definitive information on the effect of low sodium dialysis fluids on heart structure and function, or patient quality of life and survival.
Conclusions
We are uncertain about whether low sodium in dialysis fluid improves overall health and well-being for people on haemodialysis, since there are a mixture of probably good and bad effects, and available research studies were not designed (or designed well-enough) to learn about effects of the intervention on the heart or on overall patient health and well-being. Larger and up-to-date definitive studies are needed to evaluate the medium to long-term effects of low sodium levels in dialysis fluid, and better inform clinical practice.
It is likely that low dialysate [Na+] reduces intradialytic weight gain and BP, which are effects directionally associated with improved outcomes. However, the intervention probably also increases intradialytic hypotension and reduces serum [Na+], effects that are associated with increased mortality risk. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.
Cardiovascular (CV) disease is the leading cause of death in dialysis patients, and strongly associated with fluid overload and hypertension. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing CV morbidity and mortality.
This review evaluated harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients.
We searched the Cochrane Kidney and Transplant Register of Studies up to 7 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included.
Two investigators independently screened studies for inclusion and extracted data. Statistical analyses were performed using random effects models, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using GRADE.
We included 12 studies randomising 310 patients, with data available for 266 patients after dropout. All but one study evaluated a fixed concentration of low dialysate [Na+], and one profiled dialysate [Na+]. Three studies were parallel group, and the remaining nine cross-over. Of the latter, only two used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 3 (3, 8.5) weeks. Two were of a single HD session, and two of a single week's HD. Half of the studies were conducted prior to 2000, and five reported use of obsolete HD practices. Risks of bias in the included studies were often high or unclear, lowering confidence in the results.
Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "efficacy" endpoints: reduced interdialytic weight gain (10 studies: MD -0.35 kg, 95% CI -0.18 to -0.51; high certainty evidence); probably reduced predialysis mean arterial blood pressure (BP) (4 studies: MD -3.58 mmHg, 95% CI -5.46 to -1.69; moderate certainty evidence); probably reduced postdialysis mean arterial BP (MAP) (4 studies: MD -3.26 mmHg, 95% CI -1.70 to -4.82; moderate certainty evidence); probably reduced predialysis serum [Na+] (7 studies: MD -1.69 mM, 95% CI -2.36 to -1.02; moderate certainty evidence); may have reduced antihypertensive medication (2 studies: SMD -0.67 SD, 95% CI -1.07 to -0.28; low certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "safety" endpoints: probably increased intradialytic hypotension events (9 studies: RR 1.56, 95% 1.17 to 2.07; moderate certainty evidence); probably increased intradialytic cramps (6 studies: RR 1.77, 95% 1.15 to 2.73; moderate certainty evidence).
Compared to neutral or high dialysate [Na+], low dialysate [Na+] may make little or no difference to: intradialytic BP (2 studies: MD for systolic BP -3.99 mmHg, 95% CI -17.96 to 9.99; diastolic BP 1.33 mmHg, 95% CI -6.29 to 8.95; low certainty evidence); interdialytic BP (2 studies:, MD for systolic BP 0.17 mmHg, 95% CI -5.42 to 5.08; diastolic BP -2.00 mmHg, 95% CI -4.84 to 0.84; low certainty evidence); dietary salt intake (2 studies: MD -0.21g/d, 95% CI -0.48 to 0.06; low certainty evidence).
Due to very low quality of evidence, it is uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular mass or volumes, thirst or fatigue. Studies did not examine cardiovascular or all-cause mortality, cardiovascular events, or hospitalisation.