Why Serum Aluminum is Low in Third-Spacing
Serum aluminum is NOT typically low in third-spacing states—this is a misconception. The evidence shows that aluminum is approximately 80-90% protein-bound in plasma (primarily to transferrin), and third-spacing does not selectively sequester aluminum away from the serum compartment 1, 2.
Aluminum Distribution and Protein Binding
The fundamental biochemistry of aluminum explains why third-spacing does not lower serum levels:
- Aluminum is 80-90% protein-bound in plasma, primarily to transferrin, with only 20% existing as free, ultrafilterable aluminum 1, 2.
- Protein-bound aluminum remains in the vascular compartment during third-spacing because large protein molecules do not readily cross into interstitial fluid 2.
- Studies measuring simultaneous plasma and ultrafiltrate aluminum demonstrate that the protein-bound fraction stays in circulation even during dialysis, which creates far more dramatic fluid shifts than typical third-spacing 2.
What Actually Affects Serum Aluminum Levels
The K/DOQI guidelines and supporting research clarify what truly influences plasma aluminum:
- Plasma aluminum levels reflect recent aluminum exposure, not total body stores 1.
- Serum levels rise with aluminum intake from oral aluminum hydroxide or contaminated dialysate, and fall when these sources are removed 1.
- In dialysis patients, plasma aluminum decreased from 105 ± 21 µg/L to 34 ± 11 µg/L over 8 months after stopping aluminum gels—a slow decline reflecting mobilization from tissue stores, not redistribution into third spaces 1.
Clinical Scenarios That May Create Confusion
Several situations in critically ill patients might create the false impression of "low" aluminum:
- Hypoalbuminemia reduces total measured aluminum because less carrier protein is available, but this represents a measurement artifact rather than true aluminum depletion 1.
- Hemodialysis with high-flux membranes can lower plasma aluminum by 15-20% per session when dialysate aluminum is very low (<0.3 µmol/L), but this is active removal, not redistribution 2.
- Dilution from aggressive fluid resuscitation in sepsis or burns may transiently lower concentrations of all plasma constituents, including aluminum, but this is a volume effect 2.
Key Clinical Pitfall to Avoid
Do not assume aluminum toxicity is absent based on a single low or normal serum level in a critically ill patient with third-spacing. The K/DOQI guidelines emphasize that plasma aluminum poorly predicts bone aluminum stores and total body burden 1, 3. A study of 258 dialysis patients found that 14.2% with plasma aluminum <40 µg/L still had aluminum bone disease on biopsy, demonstrating that serum levels can be misleadingly reassuring 3.
What to Monitor Instead
In patients at risk for aluminum toxicity (dialysis, chronic aluminum hydroxide use):
- Measure serum aluminum every 6 months during ongoing exposure 1, 4.
- Serum aluminum >60 µg/L predicts aluminum bone disease with 82% sensitivity and 86% specificity—this threshold matters far more than transient fluctuations from fluid shifts 4, 3.
- Consider deferoxamine (DFO) stimulation testing (5 mg/kg) if bone disease is suspected despite normal baseline levels, though this carries risks of mucormycosis and should be reserved for symptomatic patients 1.