What causes intradialytic hypoglycemia?

Causes of Intradialytic Hypoglycemia

Intradialytic hypoglycemia results from multiple interconnected mechanisms, with decreased renal gluconeogenesis, impaired insulin clearance, glucose loss to dialysate, and increased erythrocyte glucose uptake during hemodialysis being the primary culprits. 1

Primary Pathophysiologic Mechanisms

Renal and Metabolic Dysfunction

• Decreased gluconeogenesis by the kidneys is a fundamental cause, as the kidneys normally contribute 20-40% of overall glucose production, which can increase two- to threefold during fasting or hypoglycemia 1, 2
• Impaired insulin clearance occurs because kidneys are responsible for a larger proportion of exogenous insulin metabolism (bypassing hepatic first-pass metabolism), leading to prolonged insulin action 1
• Reduced insulin degradation by the kidney, liver, and muscle due to uremia further extends insulin half-life 1

Dialysis-Specific Mechanisms

• Glucose loss to the dialysate is a major contributor, with mean glucose losses of approximately 9.2 g/hour during hemodialysis with glucose-free dialysate 3
• Increased erythrocyte glucose uptake during hemodialysis creates an additional glucose sink that depletes plasma glucose 1
• Dialysate glucose concentration is the main determinant of plasma glucose levels after hemodialysis, with glucose-free or low-glucose dialysate (<100 mg/dL) significantly increasing hypoglycemia risk 1, 4, 5

Secondary Contributing Factors

Hormonal and Counterregulatory Dysfunction

• Impaired counterregulatory hormone responses (cortisol, growth hormone, glucagon, epinephrine) result in blunted hormonal responses to falling glucose levels 1, 2, 3
• The hormonal response failure means patients cannot mount appropriate physiologic defenses against hypoglycemia 3

Nutritional and Clinical Factors

• Nutritional deprivation is both a cause and consequence of hypoglycemia in dialysis patients, with poor nutritional status being particularly common 1, 2
• Pre-dialysis glycemia levels strongly predict intradialytic hypoglycemia risk, with patients having pre-dialysis glucose ≤140 mg/dL at substantially higher risk 5
• Medication effects including insulin therapy and oral hypoglycemic agents (especially sulfonylureas) are exacerbated by the above mechanisms 1

Variability in Treatment

• Frequent treatment/dose changes by patients or medical staff create unpredictable exposure to antihyperglycemic agents 1
• Interruptions in nutritional intake during dialysis sessions compound the glucose deficit 1, 6

Critical Clinical Considerations

Asymptomatic Hypoglycemia

• Most intradialytic hypoglycemia is asymptomatic, with studies showing 21% of patients experiencing hypoglycemia (glucose <70 mg/dL) without any symptoms 7
• Even with dialysate containing 100-150 mg/dL glucose, 50% of patients had sensor glucose levels fall below the dialysate glucose concentration 7
• Elderly patients particularly fail to perceive neuroglycopenic and autonomic hypoglycemic symptoms despite comparable reaction time prolongation 1

High-Risk Patient Profiles

• Patients with pre-dialysis glucose ≤100-140 mg/dL are at highest risk and require preventive interventions 2, 5
• Diabetic patients on insulin or sulfonylureas face compounded risk from both medication effects and dialysis-related mechanisms 1
• Patients with acute kidney injury have additional risk due to decreased insulin clearance 1

Dialysate Selection Impact

• Glucose-free dialysate creates a catabolic state similar to fasting and should be avoided in diabetic patients 8, 3
• Dialysate with 55 mg/dL glucose does not prevent hypoglycemia and performs similarly to glucose-free solutions 4
• Dialysate containing at least 90-100 mg/dL glucose is necessary to prevent hypoglycemia in most patients 4, 3

Common Pitfalls to Avoid

• Failing to recognize that hypoglycemia can occur even with glucose-containing dialysate (100-150 mg/dL) 7
• Not adjusting insulin doses when transitioning patients from earlier CKD stages to dialysis, as insulin requirements typically decrease by 40-50% 1
• Continuing the same antihyperglycemic regimen without accounting for decreased renal clearance 1
• Relying on patient symptoms to detect hypoglycemia, as most episodes are asymptomatic 7, 3
• Not providing carbohydrate-rich snacks during dialysis for patients with pre-dialysis glucose ≤100 mg/dL 2