Epidemiology

Etiology

↓ Production of urine → ↑ extracellular fluid volume → total-body volume overload
↓ Excretion of waste products (e.g., urea, drugs)
↓ Excretion of phosphate → hyperphosphatemia
- During the early stages of CKD, plasma phosphate levels will typically be normal due to the increased secretion of fibroblast growth factor 23 (FGF23).
  - FGF23 is produced by osteoblasts in response to initial hyperphosphatemia and increased calcitriol.
  - Increased secretion of FGF23 leads to increased phosphate secretion and suppressed conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
  - In advanced CKD, the effects of FGF 23 subside (most likely due to development of resistance in target tissues).
↓ Maintenance of acid-base balance → metabolic acidosis
↓ Maintenance of electrolyte concentrations → electrolyte imbalances (e.g., Na⁺ retention)

↓ Hydroxylation of calcifediol → ↓ production of calcitriol → (in combination with ↓ excretion of phosphate) → ↓ serum Ca²⁺ → ↑ PTH
↓ Erythropoietin → ↓ stimulation of erythropoiesis

Definition: Uremia is defined as the accumulation of toxic substances due to decreased renal excretion. These toxic substances are mostly metabolites of proteins such as urea, creatinine, β2 microglobulin, and parathyroid hormone.
Constitutional symptoms
- Fatigue
- Weakness
- Headaches
Gastrointestinal symptoms
- Nausea and vomiting
- Loss of appetite
- Uremic fetor: characteristic ammonia- or urine-like breath odor
Dermatological manifestations
- Pruritus
  - Accumulation of histamine
- Skin color changes (e.g., hyperpigmentation, pallor due to anemia)
- Uremic frost: uremia leads to high levels of urea secreted in the sweat, the evaporation of which may result in tiny crystallized yellow-white urea deposits on the skin.
Serositis
- Uremic pericarditis: a complication of chronic kidney disease that causes fibrinous pericarditis
  - Clinical features: chest pain worsened by inhalation
  - Physical examination findings
    - Friction rub on auscultation
    - ECG changes normally seen in nonuremic pericarditis (e.g., diffuse ST-segment elevation) are not usually seen.
- Pleuritis
Neurological symptoms
- Asterixis
- Signs of uremic encephalopathy
  - Seizures
  - Somnolence
  - Coma
- Peripheral neuropathy → paresthesias
Hematologic symptoms
- Anemia
- Leukocyte dysfunction → ↑ risk of infection
- ↑ Bleeding tendency caused by abnormal platelet adhesion and aggregation
  - See Urea cycle
  - Normal platelet count, PT, aPTT; ↑ bleeding time

Pathophysiology: ↓ synthesis of erythropoietin → ↓ stimulation of RBC production → normocytic, normochromic anemia
Management
- Consider erythropoietin-stimulating agents (ESAs): for patients with Hb < 10.0 g/dL
  - Adverse effects: ↑ risk of thromboembolism; ↑ risk of hypertension