Temporal Dissociation Between Intravascular Albumin Mass and Transcapillary Escape Dynamics in Sepsis: A Longitudinal...

Area of Science:

• Critical Care Medicine
• Renal Physiology
• Biochemistry

Background:

• Sepsis disrupts albumin homeostasis through capillary leak and impaired recovery mechanisms (synthesis, lymphatic return).
• Clinical assessment of these dynamic processes in sepsis is challenging.
• Evaluating albumin escape dynamics and mass balance together may clarify their temporal interplay.

Purpose of the Study:

• To jointly evaluate ratio-based transcapillary escape rate (TER)-like dynamics and mass-based net albumin leakage (NAL) in sepsis.
• To clarify the temporal interplay between albumin leak and recovery mechanisms in sepsis patients.
• To develop a pragmatic clinical framework for albumin homeostasis phenotyping.

Main Methods:

• Prospective longitudinal cohort study of 389 sepsis patients.
• Serial daily sampling (up to five reassessments) to derive TER-like index (hourly % change in albumin/hemoglobin ratio) and NAL (change in intravascular albumin mass normalized to plasma volume).
• Analysis using generalized estimating equations (GEE), patient-level slope analyses, and state-transition analyses.

Main Results:

• The TER-like index peaked early (day 1) and became negative by day 5, indicating reduced capillary leak over time.
• Net albumin leakage (NAL) was frequently negative and heterogeneous, with 37.5% of observations showing NAL ≥ 0.
• TER-like index and NAL were inversely correlated (ρ = -0.54, p < 0.001), with significant time-varying effects (interaction p < 0.01).

Conclusions:

• Transcapillary escape rate (TER)-like dynamics attenuate early in sepsis, but net intravascular albumin balance often remains negative.
• This suggests a temporal uncoupling between albumin 'leak' and recovery processes in sepsis.
• An integrated TER-like index and NAL assessment provides a practical framework for phenotyping albumin homeostasis using routine data.