Low dialysate sodium levels for chronic haemodialysis

Cardiovascular (CV) disease is the leading cause of death in dialysis patients and is strongly associated with fluid overload and hypertension. It is plausible that low dialysate sodium ion concentration [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension and ultimately reducing CV morbidity and death. This is an update of a review first published in 2019.

This review evaluated the 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 1 October 2024 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 Registry Platform (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 authors independently screened studies for inclusion and extracted data. Statistical analyses were performed using the random-effects model, 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 Grades of Recommendation, Assessment, Development and Evaluation (GRADE).

We included 17 studies randomising 509 patients, with data available for 452 patients after dropouts. All but three studies evaluated a fixed concentration of low dialysate [Na+], with one using profiled dialysate [Na+] and two using individualised dialysate [Na+]. Five were parallel group studies, and 12 were cross-over studies. Of the latter, only six used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 4 (4 to 16) weeks. Two were of a single HD session and two of a single week's HD. Seven studies were conducted prior to 2000, and six reported the use of obsolete HD practices. Other than for indirectness arising from older studies, risks of bias in the included studies were generally low. Compared to neutral or high dialysate [Na+] (≥ 138 mM), low dialysate [Na+] (< 138 mM) reduces interdialytic weight gain (14 studies, 515 participants: MD -0.36 kg, 95% CI -0.50 to -0.22; high certainty evidence) and antihypertensive medication use (5 studies, 241 participants: SMD -0.37, 95% CI -0.64 to -0.1; high certainty evidence), and probably reduces left ventricular mass index (2 studies, 143 participants: MD -7.65 g/m², 95% CI -14.48 to -0.83; moderate certainty evidence), predialysis mean arterial pressure (MAP) (5 studies, 232 participants: MD -3.39 mm Hg, 95% CI -5.17 to -1.61; moderate certainty evidence), postdialysis MAP (5 studies, 226 participants: MD -3.17 mm Hg, 95% CI -4.68 to 1.67; moderate certainty evidence), predialysis serum [Na+] (11 studies, 435 participants: MD -1.26 mM, 95% CI -1.81 to -0.72; moderate certainty evidence) and postdialysis serum [Na+] (6 studies, 188 participants: MD -3.09 mM, 95% CI -4.29 to -1.88; moderate certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] probably increases intradialytic hypotension events (13 studies, 15,764 HD sessions: RR 1.58, 95% 1.25 to 2.01; moderate certainty evidence) and intradialytic cramps (10 studies, 14,559 HD sessions: RR 1.84, 95% 1.29 to 2.64; moderate certainty evidence). Effect size for important outcomes were generally greater with low dialysate [Na+] compared to high compared with neutral dialysate [Na+], although formal hypothesis testing identifies that the difference was only certain for postdialysis serum [Na+]. Compared to neutral or high dialysate [Na+], it is uncertain whether low dialysate [Na+] affects intradialytic or interdialytic MAP, and dietary salt intake. It is also uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular volumes, or fatigue. Studies did not examine CV or all-cause death, CV events, or hospitalisation.

Low dialysate [Na+] reduces intradialytic weight gain and probably blood pressure, which are effects directionally associated with improved outcomes. However, the intervention probably increases intradialytic hypotension and probably reduces serum [Na+], effects that are associated with an increased risk of death. 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.