Lipemia-induced pseudohyponatremia: Analytical bias beyond manufacturer claims

Lipemia-induced sodium underestimation can introduce a clinically relevant analytic bias in sodium measurements. In this study, we aimed to evaluate the clinical impact of lipemia on sodium measurements, investigate thresholds for sodium underestimation due to lipemia, and compare manufacturer-recommended interference limits with actual clinical data.

In vitro interference experiments were conducted with Intralipid® and measuring sodium via indirect ISE (Cobas Pro, Roche Diagnostics) in venous plasma and evaluated against analytical acceptance limits (±2.4 mmol/L) and the Clinical Laboratory Improvement Amendments (CLIA) total allowable error (TEa; ±4.0 mmol/L). In parallel, we analyzed 32,603 paired arterial whole blood (direct ISE) and venous plasma (indirect ISE) sodium measurements from clinical samples collected over five years (in vivo interference). The relationship between sodium bias (ΔNa) and lipemic index was assessed.

Intralipid®-spiked samples exceeded the analytical and CLIA limits at lipemic indices of ∼300 and ∼500, respectively, well below manufacturer-stated thresholds (>2000). In clinical samples, sodium bias was greater than in spiked plasma where ΔNa exceeded analytical limits at L-indices >100 and CLIA TEa at >200.

Endogenous lipemia causes clinically relevant sodium underestimation when measured via indirect ISE at lipemic indices substantially lower than manufacturer thresholds and in in vitro interference experiments. We recommend that manufacturers update their interference studies, and that laboratories evaluate their lipemic thresholds through retrospective data analysis, in accordance with ISO 15189:2022.