What are the variations in citrate concentration in dialysate for patients undergoing hemodialysis and how much citrate remains after a dialysis session?

Citrate Content in Dialysate and Retention During Hemodialysis

Citrate is not a standard component of conventional hemodialysis dialysate; rather, it is used as a regional anticoagulant infused into the arterial line of the extracorporeal circuit, with the vast majority (83%) removed by dialysis itself, leaving minimal systemic citrate load.

Citrate as Regional Anticoagulation (Not Standard Dialysate Component)

Citrate is not typically present in standard dialysate solutions. Instead, it serves as an anticoagulant alternative to heparin, particularly for patients at high bleeding risk 1.

Common Citrate Formulations and Concentrations

ACD-A (Acid Citrate Dextrose-A):

• Contains 2.2% citrate plus 2.45% dextrose 1
• Provides both anticoagulation and caloric contribution

Trisodium Citrate (TSC):

• Available as 4% hypertonic solution 1
• Also available as 1.6 mol/L hypertonic solution 2
• Used with conventional calcium-containing dialysate 2, 3

Diluted Citrate Solutions:

• Modern protocols use 12 or 18 mmol/L concentrations 1
• Often combined with calcium-free dialysate 4, 5

Isotonic Citrate (15% Na₃ citrate):

• Infused at 80-100 mL/hour 6
• Requires calcium-free dialysate for optimal anticoagulation 6

Citrate Removal and Systemic Load During Dialysis

Dialytic Removal Efficiency

The majority of citrate is removed by the dialysis procedure itself:

• 83 ± 5% of infused citrate is eliminated through dialysis 4
• Dialytic removal constitutes the major elimination pathway 4
• Only 17% reaches systemic circulation for hepatic metabolism 4

Systemic Citrate Burden

Minimal citrate accumulation occurs in patients with normal liver function:

• Systemic citrate load: 17 ± 7 mmol per 4-hour treatment 4
• Systemic citrate concentration: 0.3 ± 0.15 mmol/L 4
• Citrate reaching systemic circulation is metabolized primarily in liver, kidney, and skeletal muscle 1

Energy Contribution from Citrate

Citrate provides significant caloric intake as a metabolic substrate:

• Citrate yields 0.59 kcal/mmol (3 kcal/g) when metabolized 1
• Each mmol of citrate generates 3 mmol of bicarbonate 1
• Does not require insulin for cellular uptake 1

Total energy delivery varies by protocol:

• With ACD-A and high-lactate replacement fluids: up to 1,300 kcal/day 1
• With CVVHDF using ACD-A and glucose-containing fluids: average 513 kcal/day (218 kcal from citrate, 295 kcal from glucose) 1
• With SLED (sustained low-efficiency dialysis): only 100-300 kcal/day due to enhanced citrate removal 1

Dialysate Calcium Considerations with Citrate Use

Calcium-Free Dialysate Protocols

When using calcium-free dialysate with citrate anticoagulation:

• Substantial dialytic calcium loss occurs: 43 ± 4 mmol per 4-hour treatment 4
• Citrate increases diffusible calcium to 80% of total calcium 4
• Separate calcium chloride infusion is mandatory to prevent hypocalcemia 4, 5
• Provides superior anticoagulation compared to calcium-containing dialysate 6

Anticoagulation efficacy with calcium-free dialysate:

• Dialyzer clotting score: 4.5 ± 0.6 out of 5 6
• Ionized calcium at dialyzer inlet: 0.34 ± 0.17 mmol/L 6
• 99.6% of treatments completed successfully 5

Calcium-Containing Dialysate Protocols

Using conventional calcium-containing dialysate (1.25 mmol/L) with citrate:

• Significantly worse anticoagulation: dialyzer score 2.6 ± 1.04 (p<0.01) 6
• 16% of treatments terminated prematurely due to clotting 6
• Ionized calcium at dialyzer outlet rises to 0.63 ± 0.11 mmol/L 6
• Simpler procedure but higher clotting risk 2, 3

Hypertonic TSC with calcium-containing dialysate:

• Clotting occurred in 8.87% of sessions 3
• Early termination required in only 1.48% 3
• No systemic anticoagulation or citrate toxicity observed 3

Clinical Implications and Safety Monitoring

Critical Safety Measures

Calcium monitoring is paramount:

• Hypocalcemia is very likely with calcium-free dialysate unless calcium is re-infused 4
• Calcium supplementation should correlate with dialytic losses 4
• Starting calcium supplementation rate should be based on hematocrit and total calcium 4

Citrate accumulation is unlikely to cause hypocalcemia:

• Most citrate is removed by dialysis before reaching systemic circulation 4
• Hypocalcemia results from dialytic calcium losses, not citrate accumulation 4

Common Pitfalls to Avoid

Central venous catheter use:

• May cause paradoxical ionized calcium measurements due to recirculation 5
• Measured ionized calcium levels should be interpreted with caution 5

Inadequate calcium replacement:

• Calcium dialytic losses depend on total calcium and hematocrit 4
• Positive calcium balance (approximately +5 mmol) maintains stable systemic concentrations 4

Standard Dialysate Calcium for Non-Citrate Protocols

For patients NOT using citrate anticoagulation, particularly those on intensive hemodialysis:

The Canadian Society of Nephrology recommends dialysate calcium of 1.50 mmol/L or higher to maintain neutral calcium balance while avoiding hypercalcemia and PTH oversuppression 1. This applies specifically to long or long-frequent hemodialysis patients who discontinue calcium-based phosphate binders 1.