A dialysis patient's blood contains a "toxic stew" of 300+ identified uremic retention solutes. Kt/V only measures urea — 1 compound. The cystine, homocysteine, indoxyl sulfate, p-cresyl sulfate, AGEs, cytokines, and PTH fragments are what actually cause the itching, fatigue, CV death, neuropathy, and sudden crashes.
Dialysis removes these, but levels still spike between sessions
| Compound | Why it matters |
|---|---|
| Urea | Direct neurotoxin at high levels; nausea, fatigue, bleeding tendency |
| Creatinine | Marker, but not toxic itself |
| Uric acid | Gout, CV risk, endothelial dysfunction |
| Guanidines | Guanidinosuccinic acid, methylguanidine. Neurotoxic, inhibit NOS → hypertension, seizures, coma |
| Oxalate | Calcium oxalate deposits in vessels, heart, joints. Causes arthropathy, CV disease |
| Phosphate | Vascular calcification, calciphylaxis, secondary HPT, CV death |
| Sulfate, organic acids | Metabolic acidosis, bone buffering, fatigue |
| Trimethylamine-N-oxide (TMAO) | Gut-derived. Accelerates atherosclerosis, MI, stroke risk |
Poorly removed by low-flux HD. Partially removed by high-flux/HDF/MCO
| Compound | Molecular weight | Why it matters |
|---|---|---|
| β2-microglobulin | 11.8 kDa | Dialysis-related amyloidosis: carpal tunnel, bone cysts, shoulder pain |
| Cystatin C | 13 kDa | Marker of GFR, but also promotes vascular inflammation |
| Cystine | 240 Da (dimer) | Cystine crystals deposit in kidneys, eyes, organs in cystinosis. In ESRD, oxidized cysteine → cystine. Contributes to oxidative stress |
| Homocysteine | 135 Da | Potent CV toxin. ↑↑ in ESRD. Damages endothelium, ↑ thrombosis, MI, stroke. Dialysis removes only ∼30% |
| Advanced Glycation End-products (AGEs) | Various | Pentosidine, carboxymethyllysine. Cross-link proteins → stiff vessels, neuropathy, skin changes, cataracts |
| Cytokines | 17-26 kDa | IL-6, TNF-α, IL-1β. Chronic inflammation, malnutrition, ESA resistance, CV death |
| Complement Factor D | 24 kDa | Amplifies complement cascade. Inflammation, CV risk |
| Leptin | 16 kDa | Anorexia, malnutrition, cachexia in dialysis patients |
| Adiponectin, resistin | Various | Dysregulated glucose/lipid metabolism |
| Parathyroid hormone fragments | 7-9 kDa | Bone disease, CV calcification, pruritus |
| α1-microglobulin | 33 kDa | Oxidative stress marker |
| YKL-40 | 40 kDa | Fibrosis, inflammation, CV disease |
∼90% albumin-bound → dialysis removes <50% even with HDF
| Compound | Molecular weight | Why it matters |
|---|---|---|
| Indoxyl sulfate | 213 Da | CV toxin #1. Induces endothelial dysfunction, vascular smooth muscle calcification, fibrosis, LVH. Drives MI/sudden death |
| p-Cresyl sulfate | 188 Da | CV toxin, immune dysfunction, insulin resistance. Correlates with mortality |
| Indole-3-acetic acid | 175 Da | Neurotoxic, inhibits platelet function |
| Phenols | Various | Phenol, p-cresol. CNS toxicity, immune suppression |
| Hippuric acid | 179 Da | Inhibits glucose utilization, neurologic effects |
| CMPF | ~240 Da | 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid. Inhibits drug binding to albumin, worsens uremic toxicity |
| Kynurenines | Various | From tryptophan. Immune suppression, vascular disease, neurologic |
| Compound | Why it matters |
|---|---|
| Insulin | Kidneys degrade 30-40%. In ESRD: "burned-out diabetes" → sudden hypoglycemia, seizures, VF |
| Glucagon, gastrin | GI symptoms, glucose volatility |
| Growth hormone, prolactin | ↑ levels → insulin resistance, sexual dysfunction |
| PTH 1-84 + fragments | Bone disease, CV calcification, pruritus, myopathy |
| FGF-23 | 32 kDa. LVH, CV mortality, phosphate regulation lost |
| Compound | Why it matters |
|---|---|
| Asymmetric dimethylarginine (ADMA) | 202 Da. Potent NOS inhibitor → hypertension, CV events |
| Symmetric dimethylarginine (SDMA) | Inhibits NO, linked to CV disease |
| Polyamines | Spermine, spermidine. Neurotoxic, inhibit erythropoiesis |
| Myoinositol | Peripheral neuropathy |
| Dinucleoside polyphosphates | Vasoconstrictors → hypertension |
| Compound | Source | Why it matters |
|---|---|---|
| Endotoxin fragments, bDNAF | Biofilm in water | Chronic inflammation, ↑IL-6/CRP, CV disease, ESA resistance |
| Aluminum | Water DI failure | Dialysis dementia, osteomalacia, anemia |
| Chloramine | Carbon failure | Hemolysis, anemia |
A dialysis patient's blood contains a "toxic stew" of 300+ identified uremic retention solutes.
Kt/V only measures urea — 1 compound. The cystine, homocysteine, indoxyl sulfate, p-cresyl sulfate, AGEs, cytokines, and PTH fragments are what actually cause the itching, fatigue, CV death, neuropathy, and sudden crashes.
That's why a "stable" patient can have an MI, VF, or severe hypoglycemia at any moment. The kidney failed at removing all these, not just urea. Dialysis can't catch up.
Policy · Version 2026-09-26 · Hemodialysis Unit
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Aligned with KDOQI, AAMI/ISO, CDC, MOH-Jordan 2023, JCI 8th Ed.