Why Do the Mechanistic Actions of Albumin Not Translate Into Tangible Clinical Benefits?

Albumin has only reduced crude mortality in one randomized controlled trial conducted to date. This raises the question as to why potentially beneficial oncotic and pleiotropic properties of albumin do not consistently translate into clinically important outcomes. Four postulated explanations are provided as to why the theoretical advantages of albumin are not apparent in clinical trials: diminished oncotic action due to leakage of albumin from the intravascular compartment, modification of the pleiotropic properties of albumin both in vitro and in vivo, the ability of other plasma proteins to take over the major functions of albumin, and possible adverse effects.