Uraemia and uraemic toxins

Question 1

What is uraemia?

Answer 1

Clinical sydrome with various symptoms that arises as a result of progressive kindey failure

Question 2

What are the characteristics of uraemia?

Answer 2

Build up of uraemic toxins

Solutes become retained as a result of declining kidney function

Symptoms are non specific - loss of apetite, nausea, vomiting

Question 3

Is it known which uraemic toxins are the source of which symtoms?

Answer 3

No

Question 4

How does the build up of the uraemic toxins lead to kidney damage?

Answer 4

Molecules cause inflammation

Question 5

What are ways to classify uraemic toxins?

Answer 5

Size

They way they are carried around by the body

Question 6

What are examples of uraemic toxins?

Answer 6

Urea - small, water soluble

Phenols - small, lipid soluble or protein bound

Beta 2 microglobulin - large molecule

Question 7

Which molecule was originally thought of as the cause of uraemia?

Answer 7

Urea

Question 8

What are some features of urea?

Answer 8

Osmotically active - rapid changes in concentration leads to water movement

Used to monitor effectiveness of dialysis - urea clearance

Very non-toxic molecule

Question 9

How is it proven that urea does not play a major role in uremia?

Answer 9

Increased removal of urea does not have a major impact in renal failure

Addition of urae to dialyste does not induce symptoms of uraemia

Question 10

What is the source of many uraemic toxins?

Answer 10

Related to nitrogen breakdown

Question 11

What happens to carbohydrates and proteins not digested in the upper GI?

Answer 11

The colon salvages the energy from the undigested carbohydrates and nitrogen from the undigested proteins

Question 12

What happens to proteins along the GI tract?

Answer 12

Digested into peptides in the gut

Peptides are acted upon in the large intestine by bacteria

Nitrogenous wastes products are formed

Question 13

What is P-cresyl sulphate and Indoxyl sulphate?

Answer 13

Amino acids are broken down into PCS and IS by gut bacteria

Question 14

Why are PCS and IS not easily removed by dialysis?

Answer 14

They are protein bound

Question 15

What is the effect of PCS and IS in the kidneys?

Answer 15

Pro-inflammatory effects on various cells

Endothelial cells, epithelial cells and leukocytes

Question 16

Where do PCS and IS become protein bound?

Answer 16

In the kidneys

Question 17

What happens when PCS and IS become protein bound?

Answer 17

They recirculate and worsen kidney failure

Question 18

What is AST-120?

Answer 18

Oral sorbent

Prevents absorption of IS and PCS from the gut

Rather than PCS and IS recirculating, they are egested via the faeces

Question 19

What is another name for PCS and IS?

Answer 19

Indole compounds

Question 20

What is the build up of uraemic toxins linked to?

Answer 20

CVD and poor survival

Question 21

What are ways to remove protein-bound substances?

Answer 21

Adsorption

Oral compounds that bind them in the gut

Question 22

What is an ADEPT device?

Answer 22

Adsorbent device that promotes toxin removal during haemodialysis

Fits in line with current dialysers

Removes protein bound uraemic toxins by non-specific adsorption from blood

Question 23

What is the ADEPT device made of?

Answer 23

Carbon-based monolith

Made by synthetic resin

Question 24

What are PCS and IS examples of?

Answer 24

Protein-bound uraemic toxins