How Citrate-Based Anticoagulation Provides Calories
Citrate provides calories because it is an intermediate metabolite of the Krebs cycle that gets metabolized in the liver, kidneys, and skeletal muscle to yield energy and bicarbonate, delivering 0.59 kcal per mmol or approximately 3 kcal per gram of citrate that reaches systemic circulation. 1
Metabolic Mechanism
Direct Energy Production
- Citrate enters cells without requiring insulin because it is already an intermediate of the tricarboxylic acid (Krebs) cycle, allowing direct cellular uptake and metabolism 1, 2
- Each mmol of citrate metabolized yields 0.59 kcal of energy plus 3 mmol of bicarbonate as metabolic byproducts 1, 2
- The primary sites of citrate metabolism are the liver (predominant), kidneys, and skeletal muscle 1, 2, 3
Net Caloric Delivery During Kidney Replacement Therapy (KRT)
- Not all administered citrate provides calories - only the citrate that reaches systemic circulation after partial removal by the dialysis filter contributes to energy balance 1
- The actual caloric load depends on the balance between total citrate administered in the extracorporeal circuit and the amount removed through the filter 1
Clinical Caloric Contribution
Quantifying Energy Delivery
The caloric contribution varies substantially based on the citrate protocol and KRT modality used:
- With ACD-A citrate solutions: Average delivery of approximately 218 kcal/day from citrate alone 1
- With trisodium citrate 4% (TSC): Net post-filter citrate delivery of approximately 135 kcal/day 4
- High-dose protocols: Can deliver up to 1300 kcal/day when using high lactate replacement fluids combined with ACD-A anticoagulation 1, 3
- Typical range across studies: 115-1300 kcal/day depending on lactate content of replacement fluids and type of anticoagulation 1
- Lower-dose protocols (SLED): Only 100-300 kcal/day needs to be factored into prescribed energy intake 1
Recent Evidence on Actual Caloric Impact
- A 2022 study using CVVHD with trisodium citrate 4% found that when accounting for glucose and lactate losses through the filter, the net caloric gain from all three macronutrients combined was only 10 kcal/day in non-hyperglycemic patients 4
- Another study calculated a mean of 196 ± 69 kcal/day from tri-sodium citrate continuous veno-venous hemofiltration 5
Critical Clinical Recommendation
Mandatory Caloric Accounting
According to ESPEN guidelines, the total energy provision from citrate, lactate, and glucose in dialysis/hemofiltration solutions MUST be included in calculations to determine total daily energy provision to avoid overfeeding. 1, 3
Practical Implementation
- Calculate citrate calories regularly as changes in filter settings (particularly citrate dose and blood flow) significantly impact calorie provision 5
- Energy substrates to account for in KRT solutions include:
Strategies to Minimize Unwanted Caloric Load
Protocol Modifications
Energy excess from KRT can be partially avoided by:
- Using protocols with lower citrate concentration solutions 1
- Employing bicarbonate as a buffer instead of lactate 1
- Using citrate solutions other than ACD-A in lower doses and without glucose 1
- Implementing diffusive PIKRT modalities like SLED, which allow increased citrate removal by the treatment itself 1
Important Caveats
When Citrate Metabolism Fails
- Citrate metabolism is dramatically impaired by hypoperfusion states, hypothermia, and hepatic insufficiency 2
- In these conditions, citrate accumulates rather than being metabolized for energy, leading to citrate toxicity and prolonged hypocalcemia 2
- Approximately 5% of patients develop signs of citrate accumulation indicated by total calcium >3 mmol/L or need for high calcium substitution 6