What are the causes of hyponatremia in patients with End-Stage Renal Disease (ESRD) on Peritoneal Dialysis (PD) and Hemodialysis (HD)?

Causes of Hyponatremia in Peritoneal Dialysis and Hemodialysis Patients

Hyponatremia in ESRD patients on dialysis results primarily from loss of residual renal function, malnutrition with intracellular potassium depletion, and in PD patients specifically, excessive use of icodextrin solutions.

Primary Mechanisms in Peritoneal Dialysis Patients

Loss of Residual Renal Function

• Declining residual renal function is the strongest independent predictor of hyponatremia in PD patients (r = 0.463, p = 0.0001), with hyponatremic patients having significantly lower RRF (1.97 ± 2.3 mL/min) compared to normonatremic patients (4.31 ± 5.01 mL/min) 1
• RRF contributes approximately 30% of total renal replacement therapy at PD initiation and still provides about 15% after 2 years, making its loss particularly impactful on sodium regulation 2
• PD preserves RRF better than HD initially, but progressive decline still occurs over time 2

Icodextrin-Related Sodium Loss

• Daily volume of instilled icodextrin correlates negatively and independently with serum sodium (r = -0.476, p = 0.0001), making it the second strongest predictor of hyponatremia 1
• The mechanism involves excessive ultrafiltration without proportional sodium removal, leading to relative sodium depletion 1

Malnutrition and Intracellular Depletion

• The fall in serum sodium correlates significantly with serum potassium (r = 0.526, p = 0.008), indicating that sodium and potassium depletion from malnutrition are important contributors 1
• Contrary to traditional assumptions, hyponatremia in PD patients is associated with weight loss (mean paired difference -1.113 kg), not weight gain, in most cases (13 of 16 patients) 1
• The change in serum sodium correlates with decreased body weight (r = 0.584, p = 0.017), supporting malnutrition as a key mechanism 1

PD-Specific Nutritional Factors

• Protein losses into peritoneal dialysate average 5-15 g/24 hours (higher during peritonitis), contributing to malnutrition 2
• Peritoneal amino acid losses average 3 g/day 2
• Anorexia from glucose absorption from dialysate reduces dietary intake 2
• Dietary protein intake often falls below 1.0 g/kg/day despite requirements of 1.2-1.3 g/kg/day 2

Primary Mechanisms in Hemodialysis Patients

Impaired Water Excretion with Residual Renal Function Loss

• Progressive loss of RRF eliminates the kidney's ability to excrete free water, making HD patients dependent on dialysis for sodium and water balance 3, 4
• The inability to dilute or concentrate urine appropriately as kidney disease progresses creates vulnerability to dysnatremias 4

Dialysis-Related Factors

• Dialysate composition errors are a critical iatrogenic cause, with faulty online conductivity monitors and handheld conductivity meters causing both hyponatremia and hypernatremia 5
• Inadequate dialysis prescription contributes to fluid overload and dilutional hyponatremia 2
• Dialysis-induced nutrient losses (amino acids, vitamins, carnitine) worsen nutritional status 2
• Nitrogen balance is typically negative on HD days due to dialysis-related catabolism 2

Malnutrition and Anorexia

• Anorexia is a major cause of undernutrition in HD patients, with most eating much less than required 2
• Protein-energy malnutrition affects 10-70% of HD patients, with moderate to severe undernutrition in more than 20% 2
• Malnutrition at dialysis initiation predicts mortality after 1 year of treatment 2
• Uraemic syndrome and HD itself create microinflammatory conditions inducing persistent protein catabolism 2

Metabolic and Hormonal Alterations

• Defective insulin degradation due to uremia affects glucose and electrolyte metabolism 2
• Impaired counterregulatory hormone responses (cortisol, growth hormone) 2
• Acidosis, hyperparathyroidism, and gastroparesis are treatable causes contributing to poor nutritional intake 2

Common Mechanisms Across Both Modalities

Water Overload vs. Depletion

• Traditional teaching emphasized water overload as the primary cause, but clinical evidence shows malnutrition-related depletion is equally or more important 1
• The incidence of hyponatremia in PD patients is 14.5%, higher than previously recognized 1

Intercurrent Illness

• Diarrhea from C. difficile infection (10-25% of antibiotic-associated diarrhea) causes sodium and water losses 6
• Vomiting and gastrointestinal losses from uremia or medications 7
• Infections increase catabolism and worsen nutritional status 2

Medication-Related Causes

• Inappropriately dosed renally-cleared medications causing gastrointestinal symptoms and reduced intake 6
• Phosphate binders causing diarrhea 6
• Opioids causing constipation with paradoxical overflow diarrhea 6

Critical Clinical Pitfalls

• Do not assume hyponatremia always indicates volume overload—in PD patients, it more commonly reflects malnutrition and sodium/potassium depletion 1
• Monitor dialysate conductivity readings carefully, as equipment errors can cause iatrogenic dysnatremias 5
• Recognize that hyponatremia incidence increases as RRF declines, requiring closer monitoring in patients with minimal urine output 1
• Assess nutritional status comprehensively when hyponatremia develops, including serum potassium, albumin, and body weight trends 1
• In severe hyponatremia requiring dialysis initiation, use modified dialysate sodium (128 mEq/L) and low blood flow (50-100 mL/min) to prevent rapid correction and osmotic demyelination syndrome 7