The normal blood sodium level is 135 to 145 milliequivalents/liter (mEq/L)1. Hyponatremia occurs when blood sodium level goes below 135 mEq/L2,3. Hyponatremia is among the most common electrolyte disorders in dialysis patients. Specially, predialytic hyponatremia is a marker that has been associated with poor outcome in dialysis patients 4,5. Importantly, change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions.is associated with mortality. Fujisali et al. evaluated pre- and post-HD SNa concentration from a Japanese Society for Dialysis Therapy Renal Data Registry of patients with ESRD. The study concluded that patients with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137–140 mEq/L) and the lowest ΔSNa (≤2 mEq/L) 6. Hyponatremia is indicative of hypotonic condition reflecting free water excess and intracellular hyperhydration. Hypotonic hyponatremia may be associated with fluid overload, but also with inflammation, malnutrition, or underlying diseases 7. Although hyponatremia may occur independently from extracellular fluid overload, the association with interdialytic weight gain suggests that hypervolemic hyponatremia may have been present in a significant percentage of patients.
Epidemiology and Etiology
Although prevalence estimates vary depending on the criteria used for the definition of hyponatremia and underlying study population characteristics (e.g., incident vs. prevalent dialysis patients, dialysis modality), epidemiologic data suggest that approximately 6% to 29% of hemodialysis have serum sodium levels ≤135 mEq/L 8,9.
The etiology of hyponatremia in ESRD is multifactorial. When hyponatremia in dialysis patients is accompanied by weight gain or increase in extracellular volume (ECV), it may be potentially due excess free water intake, hyponatremia may be further exacerbated by dysregulation of thirst, or inadequate ultrafiltration. Although infrequently observed in the dialysis population, if hyponatremia is accompanied by an ECV deficit, this may be due to a loss of sodium and potassium salts resulting from poor nutritional intake or excess losses1.
Signs and Symptoms
Clinical symptoms include nausea, headache, confusion, cognitive deficits, gait disturbances, fatigue, muscle weakness, and cramps. However, symptoms may be completely absent in mild to moderate hyponatremia (i.e., serum sodium 125–135 mEq/L). Severe hyponatremia (i.e., serum sodium <120 mEq/L) is a potentially life‐threatening disorder with severe neurological complications that can result from cerebral edema or osmotic demyelination in the context of inadequate or excessive treatment, respectively 10. Acute hyponatremia is characterized by disease onset within 48 hours of insult, whereas chronic hyponatremia gradually develops over several days to weeks.
In patients with severe acute hyponatremia, that is, hyponatremia developing in less than 48 hours, and concomitant need for acute or chronic renal replacement therapy, Arieff et al.11 suggests gradual correction of serum sodium levels due to the potential risk of cerebral edema. Symptomatic treatment with hypertonic saline (3%) has been recommended by Golper et al.12; however, this approach should be avoided in hypovolemic patients. Conventional HD with standard dialysate sodium concentrations is recommended as the treatment of choice by Golper et al.12 in acute and chronic HD patients. In patients with severe hyponatremia, Sterns et al., recommend a correction rate in acute and chronic HD patients of 4-8 mEq/L per 24 hours as in non-ESRD patients10. Additionally, a potential approach may be to lower dialysis blood flow to slow intradialytic sodium transfer to the blood. Thus, conventional HD with low blood flow, prescribing low dialysate sodium concentration, and reduced treatment time may be a simple strategy to safely correct hyponatremia in the absence of continuous renal replacement therapy options, both in acute and chronic renal failure13. Importantly, given that hyponatremia may be associated with extracellular fluid overload corresponding to a hypervolemic hyponatremic state, the Clinical Practice Guideline on Diagnosis and Treatment of Hyponatremia14 recommend assessing and managing more precisely extracellular fluid volume status and then subsequently identifying the cause of hyponatremia rather than trying to correct by adjusting dialysate sodium prescription5.
- Mayo Clinic. Hyponatremia. Published online 2020. Available from: https://www.mayoclinic.org/diseases-conditions/hyponatremia/symptoms-causes/syc-20373711#:~:text=A normal blood sodium level,Certain medications.
- Adrogué HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol. 2012;23(7):1140-1148.
- Rhee CM, Ayus JC, Kalantar-Zadeh K. Hyponatremia in the Dialysis Population. Kidney Int reports. 2019;4(6):769-780. Available from: https://pubmed.ncbi.nlm.nih.gov/31194059.
- Ye X, Kooman JP, van der Sande FM, et al. Increased mortality associated with higher pre-dialysis serum sodium variability: results of the International MONitoring Dialysis Outcome Initiative. Am J Nephrol. 2019;49(1):1-10.
- Canaud B, Van der Sande F, Kooman J. Predialysis Hyponatremia and Positive Change of Natremia Within Hemodialysis Sessions Are Strong Indicators of Poor Cardiovascular Outcome in Hemodialysis Patients. Kidney Int Reports. 2021;6(2):248-251. Available from: https://www.sciencedirect.com/science/article/pii/S2468024920318428.
- Fujisaki K, Joki N, Tanaka S, et al. Pre-dialysis Hyponatremia and Change in Serum Sodium Concentration During a Dialysis Session Are Significant Predictors of Mortality in Patients Undergoing Hemodialysis. Kidney Int reports. 2020;6(2):342-350. Available from: https://pubmed.ncbi.nlm.nih.gov/33615059.
- Dekker MJE, Marcelli D, Canaud B, et al. Unraveling the relationship between mortality, hyponatremia, inflammation and malnutrition in hemodialysis patients: results from the international MONDO initiative. Eur J Clin Nutr. 2016;70(7):779-784.
- Rhee CM, Ayus JC, Kalantar-Zadeh K. Hyponatremia in the Dialysis Population. Kidney Int reports. 2019;4(6):769-780. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31194059.
- Waikar SS, Curhan GC, Brunelli SM. Mortality associated with low serum sodium concentration in maintenance hemodialysis. Am J Med. 2011;124(1):77-84.
- Sterns RH. Treatment of Severe Hyponatremia. Clin J Am Soc Nephrol. 2018;13(4):641-649.
- Arieff AI. Hyponatremia, convulsions, respiratory arrest, and permanent brain damage after elective surgery in healthy women. N Engl J Med. 1986;314(24):1529-1535.
- Golper T, Palevsky PM, Sterns RH. Acute Hemodialysis Prescription. Published online 2018.
- Wendland EM, Kaplan AA. A proposed approach to the dialysis prescription in severely hyponatremic patients with end-stage renal disease. Semin Dial. 25(1):82-85. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21906168.
- Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014;29 Suppl 2:i1-i39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24569496.
P/N 103054-01 Rev A 05/2021