Dialyzer membranes are designed to remove uremic toxins but are semipermeable. Pore size, membrane type (low-flux vs high-flux vs MCO), and water purity determine what actually crosses. Even with ultrafilters, some substances can pass.
| Category | Examples | Molecular Weight | Clinical relevance |
|---|---|---|---|
| Small water-soluble | Urea, creatinine, uric acid, K⁺, Na⁺, Ca⁺⁺, Mg⁺⁺, phosphate, glucose | <500 Da | Routinely removed by diffusion |
| Small middle-molecules | β2-microglobulin, cystatin C, complement factor D, cytokines IL-6, TNF-α | 500 Da – 25 kDa | Removed by high-flux/MCO membranes; accumulation causes amyloidosis, inflammation |
| Large middle-molecules | α1-microglobulin, YKL-40, free light chains | ≥25 kDa | Partially removed by MCO; poor removal by standard high-flux |
| Protein-bound uremic toxins | Indoxyl sulfate, p-cresyl sulfate | ∼200 Da but 90% albumin-bound | Poor removal even with HDF; RR ∼48–53% |
These are not intended but can cross, especially with high-flux/MCO membranes and poor water quality.
| Substance | Source | Size / Notes | Evidence of crossing | Clinical effect |
|---|---|---|---|---|
| Endotoxin (LPS) | Gram-negative bacteria in water/biofilm | Intact LPS ∼10–20 kDa; fragments smaller | Anti-endotoxin antibodies in HD patients prove crossing | Pyrogenic reactions, chronic inflammation, CV disease, ↑CRP/IL-6 |
| Bacterial DNA fragments (bDNAF) | Dead bacteria in dialysate | Low-MW oligonucleotide | Can pass MCO membranes; 500 ng/mL induces IL-6 | ↑ CRP/IL-6; strong predictor of CV disease in PD patients |
| Peptidoglycan, muramyl peptides | Gram-positive cell wall fragments | <10 kDa | Suspected to cross like LPS fragments | Cytokine-inducing, micro-inflammation |
| Exotoxins, bacterial metabolites | Pseudomonas, other Gram-negatives | Variable, often <20 kDa | Suspected in outbreaks with bacteria+endotoxin | Fever, hypotension, inflammation |
These caused 217 cases and 14 deaths 1960–2007. They cross freely when present.
| Contaminant | Source | Effect if crosses | Notes |
|---|---|---|---|
| Aluminum | Exhausted DI tanks | Seizures, dialysis dementia, osteomalacia | 3 deaths |
| Chloramine | Carbon filter failure | Hemolytic anemia | 41 patients affected |
| Copper | Low pH water + copper pipes | Hemolytic syndrome | 4 fatalities |
| Fluoride | Municipal spill or exhausted DI | Fluoride intoxication | 4 deaths |
| Formaldehyde / hydrogen peroxide | Inadequate rinse after disinfection | Patient intoxication, hemolysis | Multiple cases |
| Silicates, carbonate scales | Hard water, biofilm | Deposited on membranes | May leach trace elements |
| PFAS | Environmental, membrane manufacturing | PFHpA, PFNA, PFDA, PFUnDA detected; levels vary by membrane type | Persistent pollutants; associated with kidney disease |
| Substance | Source | Notes |
|---|---|---|
| Trihalomethanes, haloacetic acids | Chlorinated municipal water + organics | Not routinely tested; small MW may cross |
| N-nitrosodimethylamine (NDMA) | Chloramine disinfection byproduct | Suspected carcinogen; can cross |
| Ozone byproducts | If ozone used in water treatment | Aldehydes, ketones; trace levels possible |
| Substance | Source | Notes |
|---|---|---|
| BPA, phthalates | Polysulfone/polyethersulfone membranes, plasticizers | Suspected endocrine disruptors; trace leaching possible |
| PVP (polyvinylpyrrolidone) | Hydrophilic agent in membranes | Can elute; some allergic reactions reported |
| Acetate | Acetate-based dialysate | Crosses freely; replaced by bicarbonate in most units but still used |
The dialyzer is not a perfect barrier.
Even with ultrapure dialysis fluid <0.03 EU/mL, endotoxin fragments, bDNAF, and trace chemicals can still cross, especially with high-flux/MCO membranes.
That’s why AAMI, ISO, and JSDT recommend ultrapure fluid for routine HD and why chronic inflammation remains common in HD patients.
Substances Crossing The Dialyzer Membrane · Version 2026-06-27 · Hemodialysis Unit
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Aligned with KDOQI, AAMI/ISO, CDC, MOH-Jordan 2023, JCI 8th Ed.