Is albumin removed by standard low‑flux or high‑flux hemodialysis or continuous renal replacement therapy in patients with acute or chronic kidney disease?

Is Albumin Dialyzable?

Albumin is minimally removed by standard low-flux hemodialysis but can be lost in clinically significant amounts with high-flux dialysis, hemodiafiltration, and especially with newer high-cut-off or medium cut-off membranes. 1, 2

Albumin Loss by Dialysis Modality

Standard Low-Flux Hemodialysis

• Albumin loss is negligible with conventional low-flux membranes, as these dialyzers were specifically designed to prevent albumin leakage while removing small solutes. 1
• The HEMO Study demonstrated that low-flux dialyzers had β2-microglobulin clearance "indistinguishable from zero," indicating minimal permeability to molecules approaching albumin size (66 kDa). 1

High-Flux Hemodialysis

• High-flux membranes allow some albumin passage, but manufacturers have optimized designs to minimize albumin leakage while maximizing middle molecule clearance. 1
• The KDOQI guidelines note that "the manufacturing industry has learned how to expand β2-microglobulin clearances while minimizing albumin leakage" in modern high-flux dialyzers. 1
• Albumin losses with standard high-flux HD are typically 4-6 grams per session, which is generally considered acceptable. 3

Hemodiafiltration (HDF)

• Post-dilution online hemodiafiltration significantly increases albumin loss compared to standard HD, particularly with high convective volumes. 3, 4
• A documented case showed albumin losses of 23.6 grams per HDF session versus 4.6 grams with standard HD using the same high-flux membrane, demonstrating a 5-fold increase with convective therapy. 3
• The convective component of HDF (29 liters in the reported case) dramatically enhances albumin passage across the membrane. 3

High-Cut-Off and Medium Cut-Off Membranes

• Newer protein-leaking membranes designed for enhanced middle molecule removal are associated with substantially increased albumin losses. 2, 5
• These membranes improve clearance of uremic toxins between 10-50 kDa but at the cost of greater albumin loss. 5
• The clinical relevance of enhanced middle molecule removal versus increased albumin loss remains undetermined. 4

Continuous Renal Replacement Therapy (CRRT)

• CRRT with standard membranes results in continuous but modest albumin loss over 24 hours. 1
• Super high-flux membranes in CRRT may increase middle molecule clearance with theoretically limited albumin loss when used in diffusive mode. 6

Clinical Significance

Impact on Serum Albumin

• Approximately 60% of hemodialysis patients have serum albumin <4.0 g/dL, with dialyzer-related albumin loss being a potentially modifiable contributor. 2
• A case report documented severe hypoalbuminemia (nadir 2.26 g/dL) developing over months with high-volume post-dilution HDF, which corrected to 3.82 g/dL after switching to standard HD with the same membrane. 3
• This demonstrates that dialysis-related albumin loss can be clinically significant and reversible with modality changes. 3

Risk Factors for Excessive Albumin Loss

• High permeability membranes (polyphenylene, high-cut-off) combined with high convective volumes create the highest risk. 3, 5
• Steam-sterilized polyphenylene membranes (e.g., Phylther HF20SD) are particularly prone to large albumin losses during post-dilution HDF. 3
• The KDOQI guidelines recommend high-flux dialyzers for patients with albumin ≤4 g/dL based on mortality benefits, but this must be balanced against albumin loss risk. 1, 7

Practical Recommendations

When to Suspect Dialysis-Related Albumin Loss

• Progressive hypoalbuminemia developing after dialysis initiation or modality change, particularly with HDF or high-cut-off membranes. 3
• Exclude other causes: nephrotic syndrome, hepatic failure, malabsorption, and protein-energy wasting. 3
• Measure albumin concentration in spent dialysate to quantify losses if clinically indicated. 3

Membrane Selection Strategy

• Use standard high-flux membranes for routine dialysis, as they provide adequate middle molecule clearance with acceptable albumin loss. 1
• Avoid high-cut-off or medium cut-off membranes in patients with baseline hypoalbuminemia (<3.5 g/dL) unless middle molecule removal benefits clearly outweigh risks. 2, 4
• Exercise caution with post-dilution HDF in patients at risk for hypoalbuminemia, particularly when using highly permeable membranes. 3, 4

Monitoring

• The acceptable upper limit of dialysis-related albumin loss remains unknown, but losses exceeding 5-6 grams per session warrant concern. 3, 4
• Serial serum albumin monitoring is essential when using convective therapies or high-permeability membranes. 3

Key Caveat

Whether hypoalbuminemia-associated mortality reflects low albumin levels per se or underlying inflammation and malnutrition remains unclear, making the clinical significance of dialysis-related albumin loss uncertain. 4 However, any additional albumin loss should theoretically be minimized in an already at-risk population. 4