UREMIA 

1️⃣ Definition

Uremia is the clinical syndrome resulting from severe reduction in glomerular filtration rate (GFR) leading to accumulation of:

  • Nitrogenous waste (urea, creatinine)
  • Middle molecules
  • Protein-bound toxins
  • Electrolyte & acid–base derangements
  • Hormonal dysfunction

It is NOT just elevated urea, but a multi-system toxic state of advanced kidney failure.

Typically seen when:

  • GFR < 15 mL/min/1.73 m²
  • Advanced AKI or CKD (Stage 5)


2️⃣ Pathophysiology of Uremia

Uremia results from accumulation of:

A. Small Water-Soluble Molecules

  • Urea
  • Creatinine
  • Guanidines
  • Phosphate

B. Middle Molecules

  • β2-microglobulin
  • Parathyroid hormone fragments
  • Advanced glycation end products

C. Protein-Bound Toxins

  • Indoxyl sulfate
  • p-Cresyl sulfate

These cause:

Mechanism

Effect

Inflammation

Endothelial dysfunction

Oxidative stress

Cardiovascular damage

Immune dysfunction

Infection risk

Platelet dysfunction

Bleeding

Neurotoxicity

Encephalopathy


3️⃣ Etiology

Uremia develops in:

A. Acute Kidney Injury (AKI)

  • Sepsis
  • Hypovolemia
  • Nephrotoxins
  • Obstruction

B. Chronic Kidney Disease (CKD Stage 5)

  • Diabetic nephropathy
  • Hypertensive nephrosclerosis
  • Glomerulonephritis
  • Polycystic kidney disease


4️⃣ Clinical Manifestations (Multi-System)

 1. Neurological – Uremic Encephalopathy

Features:

  • Fatigue
  • Confusion
  • Delirium
  • Seizures
  • Coma
  • Asterixis
  • Peripheral neuropathy
  • Restless legs

EEG: Diffuse slowing

 Reversible with dialysis.


 2. Cardiovascular

A. Uremic Pericarditis

Features:

  • Chest pain
  • Pericardial rub
  • Large effusion
  • Tamponade

 Non classic ECG ST elevation pattern

Absolute indication for dialysis.


B. Hypertension

  • Volume overload
  • RAAS activation


C. Cardiomyopathy

  • LVH
  • Dilated cardiomyopathy


 3. Hematological

A. Normocytic Normochromic Anemia

Cause:

  • Erythropoietin
  • Iron deficiency
  • Inflammation

B. Platelet Dysfunction

  • Normal count
  • Prolonged bleeding time
  • Mucosal bleeding

Mechanism:

  • Impaired platelet aggregation
  • Abnormal vWF interaction


 4. Pulmonary

Uremic Lung

  • Pulmonary edema
  • Capillary leak
  • Volume overload


 5. Gastrointestinal

  • Nausea
  • Vomiting
  • Anorexia
  • Metallic taste
  • GI bleeding
  • Uremic fetor (ammonia smell)


 6. Endocrine & Bone

CKD–Mineral Bone Disorder (CKD-MBD)

  • Hyperphosphatemia
  • Hypocalcemia
  • Secondary hyperparathyroidism
  • Renal osteodystrophy


 7. Dermatological

  • Pruritus
  • Hyperpigmentation
  • Uremic frost (rare now)


5️⃣ Laboratory Findings

Parameter

Finding

BUN

Elevated

Creatinine

Elevated

Metabolic acidosis

High anion gap

Potassium

Hyperkalemia

Phosphate

High

Calcium

Low

Hemoglobin

Low

PTH

High



8️⃣ Indications for Dialysis in Uremia

Classic mnemonic: AEIOU

Letter

Meaning

A

Acidosis (refractory metabolic)

E

Electrolyte (severe hyperkalemia)

I

Intoxication

O

Overload (pulmonary edema)

U

Uremic symptoms

Uremic Symptoms include:

  • Encephalopathy
  • Pericarditis
  • Severe bleeding
  • Persistent nausea/vomiting

 These are absolute indications.