Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement Therapy

Abstract

Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.

Keywords: acute kidney injury; albumin; chronic hemodialysis; dialysis; hemodialysis; hypotension; intradialytic hypotension; intravenous albumin; kidney replacement therapy; ultrafiltration.

Figure 1.

Metabolism of albumin and causes of hypoalbuminemia. Overview of albumin metabolism and selected mechanisms for the development of hypovolemia. Not shown is the normal breakdown of albumin, which has a t _1/2 of approximately 3 weeks. Hypoalbuminemia results from some combination of decreased production, increased losses, acute dilution (not shown), or increased shift out of the vascular space. *Increased skin and gastrointestinal losses typically occur in the context of concurrent, increased capillary leak.

Figure 2.

Albumin movement across the capillary endothelium in health and disease. (A) In the historical model of capillary fluid exchange on the basis of Starlings forces, net plasma filtration was believed to occur at the arteriolar end of the capillary due to predominant hydrostatic force (blue arrows), which then transitioned to net reabsorption as plasma reached the venular end due to increasing oncotic drive from the interstitium, back into the capillary lumen (green arrows) (additional details are in Supplemental Material). Some research now suggests that there is, in fact, little to no reabsorption at the level of the capillary in the steady state (but it still may occur during acute hypovolemia). (B and C) A simplified version of the endothelial glycocalyx in its role as a selectively permeable barrier for fluid resorption. Hydrostatic pressure is the predominant force in this new model regulated by the glycocalyx, with little to no effect from osmotic forces between the vascular lumen and the interstitium. Instead, the endothelial glycocalyx functions to create an osmotic gradient (orange arrow) between the capillary lumen and the subglycocalyx space that opposes outward shift of fluid but does not reverse the direction of fluid flow. Both the interstitium and the subglycocalyx space have low oncotic content, resulting in negligible oncotic forces between the two spaces and overall net ultrafiltration throughout plasma transit in capillary microcirculation. Fluid that has shifted into the interstitium is resorbed solely through the lymphatic system, with exceptions (including the kidneys). (D) Fluid shift in the setting of a damaged endothelial glycocalyx from stressors, including inflammation, uremia, arteriosclerosis, hyperglycemia, and hypovolemia, among many others. With a damaged endothelial glycocalyx, capillaries have increased permeability to both serum proteins and fluid, leading to increased net fluid movement into the interstitium and interstitial edema when the lymphatic drainage capacity is exceeded.