What causes a decrease in carbon dioxide (CO2) levels in a patient with end-stage renal disease (ESRD) undergoing dialysis?

Causes of Decreased CO2 Levels in Dialysis Patients

The most common cause of decreased CO2 (bicarbonate) in dialysis patients is inadequate correction of chronic metabolic acidosis, which occurs when dialysate bicarbonate concentration is insufficient or when electrolyte losses during kidney replacement therapy exceed replacement. 1, 2

Primary Mechanisms of Low CO2 in Dialysis Patients

Chronic Metabolic Acidosis (Most Common)

• Dialysis patients with end-stage renal disease develop metabolic acidosis because their kidneys cannot excrete hydrogen ions or synthesize ammonia adequately, leading to acid accumulation. 3
• The target predialysis serum bicarbonate should be maintained at ≥22 mmol/L through adjustment of dialysate bicarbonate concentration, with measurements obtained at least monthly. 2
• Bicarbonate levels below 22 mmol/L indicate inadequate dialysis prescription or insufficient oral alkali supplementation between treatments. 2, 3

Dialysis-Related Electrolyte Losses

• Intensive dialysis strategies using standard phosphate-free and low-bicarbonate dialysis solutions can cause or worsen metabolic acidosis, with prevalence of electrolyte derangements rising to 80% during prolonged kidney replacement therapy. 1
• Hypokalemia occurs in approximately 25% of patients with kidney failure started on prolonged modalities of kidney replacement therapy, proportional to the delivered dialysis dose. 1
• Hypophosphatemia, hypomagnesemia, and other electrolyte losses during continuous kidney replacement therapy contribute to metabolic derangements. 1

Dialysis-Induced Respiratory Changes (Transient)

• Hemodialysis can cause transient CO2 unloading, particularly with acetate-buffered dialysate, leading to alveolar hypoventilation and irregular breathing patterns with prolonged expiratory time. 4
• A significant increase in sensitivity to CO2 occurs immediately (within 30 minutes) following hemodialysis, returning to predialysis values within 24 hours, which can cause transient respiratory alkalosis. 5
• This dialysis-induced osmotic disequilibrium from rapid urea removal increases ventilatory response to carbon dioxide temporarily. 5

Clinical Consequences of Untreated Low CO2

Bone Disease

• Chronic metabolic acidosis alters calcium-PTH-vitamin D homeostasis, causing exaggerated bone dissolution and contributing to renal osteodystrophy. 2, 3
• Patients with normal bone biopsy results have serum bicarbonate levels around 23 mmol/L, while those with osteodystrophy have levels below 20 mmol/L. 2, 3
• Bone fractures are a relatively common manifestation of chronic metabolic acidosis in renal disease. 3

Protein Catabolism and Malnutrition

• Low CO2 levels lead to excess protein catabolism, contributing to muscle wasting and malnutrition in chronic kidney disease patients. 2, 3
• Increased protein breakdown leads to negative nitrogen balance and decreased serum albumin. 2

Secondary Hyperparathyroidism

• Acidosis worsens secondary hyperparathyroidism both biochemically and on bone biopsy findings. 3
• Patients with acidosis show progression of secondary hyperparathyroidism over 18 months compared to those with normal CO2 levels. 2, 3

Diagnostic Algorithm

Step 1: Measure predialysis serum bicarbonate (total CO2) at least monthly 2

• Normal range: 22-26 mmol/L
• Treatment threshold: <22 mmol/L
• Urgent intervention: <18 mmol/L

Step 2: Assess dialysis adequacy 1

• Review dialysate bicarbonate concentration (should be 35-38 mmol/L for most patients)
• Calculate delivered dialysis dose (Kt/V)
• Evaluate interdialytic weight gain and fluid removal patterns

Step 3: Evaluate for contributing factors 1, 2

• Dietary protein intake (high animal protein increases acid load)
• Inadequate fruit and vegetable consumption (provides alkali)
• Recent nephrotoxic insults or volume depletion episodes
• Medication review (diuretics, ACE inhibitors, ARBs)

Step 4: Rule out spurious results 6

• Delays in sample processing can cause artifactual reduction in total CO2
• Samples shipped to central laboratories may show falsely low bicarbonate levels
• Consider repeating with immediate local laboratory analysis if results seem inconsistent

Management Approach

Dialysis Prescription Adjustment (First-Line)

• Increase dialysate bicarbonate concentration to 35-38 mmol/L to prevent metabolic acidosis during kidney replacement therapy. 1, 2
• Use dialysis solutions containing potassium, phosphate, and magnesium to prevent electrolyte disorders during kidney replacement therapy. 1
• Avoid citrate-containing alkali supplements in dialysis patients exposed to aluminum salts, as citrate increases aluminum absorption and can worsen bone disease. 2, 3

Oral Alkali Supplementation

• For bicarbonate 18-22 mmol/L: Consider oral sodium bicarbonate 0.5-1.0 mEq/kg/day divided into 2-3 doses (typically 2-4 g/day or 25-50 mEq/day). 2, 7
• For bicarbonate <18 mmol/L: Initiate pharmacological treatment with oral sodium bicarbonate immediately. 2, 7
• Monitor serum bicarbonate monthly initially, then at least every 4 months once stable. 2, 7

Monitoring Parameters

• Blood pressure (sodium bicarbonate does not significantly increase blood pressure when used appropriately) 7
• Serum potassium (alkalinization drives potassium intracellularly) 7
• Fluid status and body weight 2, 7
• Calcium, phosphorus, and PTH levels (acidosis correction improves bone metabolism) 3

Critical Pitfalls to Avoid

• Do not ignore bicarbonate levels between 18-22 mmol/L—this range still causes protein catabolism and bone disease and requires intervention. 2, 3
• Never use citrate-containing alkali preparations in dialysis patients, as they dramatically increase aluminum absorption both before and during dialysis. 2, 3
• Avoid excessive ultrafiltration that causes intravascular volume depletion, as hypotensive episodes during hemodialysis accelerate loss of residual kidney function. 1
• Do not attribute all low CO2 values to chronic metabolic acidosis without considering transient dialysis-induced respiratory changes, which resolve within 24 hours. 4, 5
• Be cautious with sodium bicarbonate in patients with advanced heart failure with volume overload, severe uncontrolled hypertension, or significant edema. 7