INTRODUCTION & CLINICAL FEATURES

EPIDEMIOLOGY Uremia is a clinical syndrome

- no single symptom/sign/laboratory will reflect all

End-stage Renal Disease (ESRD) aspects

- irreversible loss of renal function

- BUN & creatinine are inaccurate markers of
- results to accumulation of toxins, and loss of
internal homeostasis
clinical syndrome of uremia
- fatal unless given renal replacement therapy:
- Reason for emergency dialysis: hyperK, severe
- Renal transplant
acid-base disturbances, pulmonary edema
- Dialysis (hemo or peritoneal)
resistant to usual tx

Uremia - ↑ urea, BUN w/ ssxs

Non-specific: anorexia, vomiting, lassitude
Azotemia - ↑ N, BUN w/o ssxs
(subtle; attributed to other things)

Severe: tremors (asterixis), altered sleep-wake

Hemodialysis cycles, disorientation, seizures or convulsions
- initial therapy in majority of adults
(severe), bleeding diathesis (platelet abnormality)

- 1/2 alive 3 years post therapy

- cardiac cause as cause of death in 1/2

Leads to death unless toxins removed by RRT

Renal transplant & Peritoneal Dialysis

- more common in children
Neurologic

- Uremic encephalopathy: cognitive defects,

PATHOPHYSIOLOGY memory loss, decreased attentiveness, slurred
speech, reversal of sleep-wake cycle, asterixis,
1. Excretory Failure
seizure, coma, symptomatic improvement with
• elevated levels of >70 chemicals in uremic dialysis

plasma cause uremic organ dysfunction

- Dialysis dementia: progressive neurologic decline,
• Urea is not the major toxin
failure to improve with dialysis, fatal

• Toxins: cyanate, guanidine, polyamines and - Subdural hematoma: headache, FND, seizure,
B2-microglobulin

coma

• most toxins are protein bound —> non- - Peripheral neuropathy: singultus (hiccups),
dialyzable

restless leg syndrome, sensorimotor neuropathy,

2. Biosynthetic Failure autonomic neuropathy

• loss of renal hormones 1,25(OH)2-vit D3 and

EPO

Cardiovascular

• 1a-hydroxylase converts Vit D to active form

- coronary artery disease

• ↓EPO —> anemia - HTN: essential htn, glomerulonephritis, renal

• ↓Vit D3 —> ↓GI Ca absorption —> artery stenosis, fluid overload

secondary hyperparathyroidism —> renal - Heart failure: fluid overload, uremic

bone disease (aka bone resorption) cardiomyopathy, high output AVF

3. Regulatory Failure - Pericarditis: uremic, dialysis related, pericardial

• oversecretion of hormones —> disruption of tamponade

normal feedback mechanism

• Uremic State
Hematologic

- ↑hormone ↓ feedback ↑ ROS

- Anemia, decreased RBC survival, decreased EPO

- ROS interacting w/ CHO, lipids, AA —> - bleeding diathesis

atherosclerosis & amyloidosis

- Immunodeficiency (humoral & cellular)

- amyloid - insoluble protein

4. [TRANS]: progressive inflammation & GI

consequences - anorexia, metallic taste, N/V

- GI bleeding

- Diverticulosis, diverticulitis

- Ascites

Renal bone disease

- Metastatic calcification (calciphylaxis)

- Hyperparathyroidism (osteitis fibrosa cystica)

- Vit D3 deficiency & aluminim intoxication

(osteomalacia)

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Stage 1-2 : still reversible

Stage 3-5: point of no return

NEUROLOGIC COMPLICATIONS
Stroke - subdural hematoma - in dialysis
patients

Uremic encephalopathy - after eliminating

structural, vascular, infectious, toxic &
metabolic causes; improves with dialysis

Dialysis dementia - progressive, evident after

2 years of dialysis. Evident after at least 2
years of dialysis therapy

Peripheral neuropathy - m/c neurologic; LE >

UE. Large fiber involvement + paresthesias
↓DTR, imapired vibration sense, muscle
wasting & weakness

CARDIOVASCULAR
COMPLICATIONS

HEMATOLOGIC COMPLICATIONS

GI COMPLICATIONS

RENAL BONE DISEASE

B2-MICROGLOBULIN
AMYLOIDOSIS

HEMODIALYSIS

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