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, creatinine. 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 | 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 of cysteine) | 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) | Pentosidine, carboxymethyllysine. Cross‑link proteins → stiff vessels, neuropathy, skin changes, cataracts |
| Cytokines | IL‑6, TNF‑α, IL‑1β ~17‑26 kDa. 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 | 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 | 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 | Neurotoxic, inhibits platelet function |
| Phenols | Phenol, p‑cresol. CNS toxicity, immune suppression |
| Hippuric acid | Inhibits glucose utilization, neurologic effects |
| 3‑Carboxy‑4‑methyl‑5‑propyl‑2‑furanpropanoic acid (CMPF) | Inhibits drug binding to albumin, worsens uremic toxicity |
| Kynurenines | 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 hypo at any moment. The kidney failed at removing all these, not just urea. Dialysis can’t catch up.