Lecture 13 - Chronic Kidney Disease

Question 1

Define CKD

Answer 1

abnormalities of kidney function or structure present for more than 3 months

Question 2

How is absorption affected in CKD?

Answer 2

Can result in an increase or decrease in BA
- reduced transporter availability for uptake from GIT
- reduced enzymtic metabolism in intestinal enterocytes

Question 3

How is distribution affected in CKD?

Answer 3

Oedema - Vd may increase
hypalbuminaemia
Increased free fraction can increase clearance and/or distribution

Question 4

Define hypalbuminaemia

Answer 4

Reduced protein binding leads to a greater free fraction of the drug
The walls that the filtrate passes through become looser - proteins can pass through and get excreted more regularly
Drugs that bind to albumin circulate around the body will be less protein bound so more of the active drug will be accessible to access the receptors - more available to produce side effects

Question 5

How is metabolism affected in CKD?

Answer 5

Decreased drug metabolism via CYP enzymes in the liver as well as the intestines
Increased free drug due to reduced protein binding - increased metabolism
Decreased metabolic functions, enzymes are inhibited by uraemic toxins

Question 6

How is excretion affected in CKD?

Answer 6

Decreased rate of GFR
Decreased rate of active secretion

Question 7

What risks do we need to be aware of in patients with CKD?

Answer 7

Risk of increased side effects and toxicity
Rick of ineffectiveness
Risk of exacerbating impacts of CKD
Risk of worsening renal function

Question 8

What are the causes of CKD?

Answer 8

Diabetes
Hypertension
Glomerulonephritis (inflamed structures in kidney)
Polycystic kidney disease and other inherited diseases
Genetic malformations
Lupus and other immune conditions
Obstructions
Repeated urinary infections

Question 9

What are the signs and symptoms of CKD?

Answer 9

Fatigue
nausea
SOB
palpitations
itch
restless legs
cramps
heartburn
fractures
frothy urine
thirst
headaches
loss of appetite
confusion
difficulty concentrating
reduce urine output

Question 10

Name the complications of CKD that require urgent/acute management

Answer 10

Fluid overload
Hyperkalaemia
Metabolic acidosis

Question 11

Name what requires long-term management to prevent further complications

Answer 11

renal bone disease
hyperparathyrodism
renal anaemia
cardiovascular risk reduction
symptom control of pruritus and cramps etc
medicines optimisation

Question 12

How is metabolic acidosis managed?

Answer 12

refer to renal specialist
IV sodium bicarbonate
dialysis

Question 13

How is fluid overload managed?

Answer 13

Fluid restriction - to reduce the risk of pulmonary oedema
Diuretics - loop, thiazide, potassium sparing
Dialysis - if severe

Question 14

How is hyperkalaemia managed?

Answer 14

Stabilise cardiac tissue - if ECG changes give calcium gluconate 10ml of 10% IV - and repeat until ECG normalises
Reduce serum potassium - increase uptake into the cells -> give 50ml of 50% glucose with 10 units of Actrapid insulin over 10 minutes. Consider giving 10-20mg of nebuliser salbutamol
Reduce potassium absorption - diet restriction and dietary potassium binders - e.g. sodium zirconium cyclosilicate, calcium resonium

Question 15

How is hyperkalaemia prevented?

Answer 15

Reduce dietary intake of K+
Review medicines pre-disposing to hyperkalaemia

Question 16

What are the benefit of ACE and ARB in CKD patients?

Answer 16

Help to protect the kidneys and preserve function in CKD
Useful in reducing protein loss on urine due to CKD

Question 17

Are ACEI/ARB stopped or continued in CKD and AKI?

Answer 17

ACEI/ARB withhold in AKI
IN CKD they are continued - reduces blood flow to the kidney so the kidneys do not have to work as hard to filter blood

Question 18

How is anaemia managed and monitored?

Answer 18

Monitor response and adjust dose to maintain Hb100-120g/L
Continue to monitor iron levels and replace to maintain 200-500mcg/L

Question 19

Define Erythropoiesis Stimulating Agent (ESAs)

Answer 19

Mimic erythropoietin to promote production of red blood cells
can be given IV or SC
Aim to maintain Hb 100-120g/l

Question 20

How is anaemia a complication in CKD?

Answer 20

The kidneys are the main site of production of erythropoietin production
Erythropoietin is the GF which promotes red blood cell formation and release of reticulocytes from the bone marrow
In CKD patients - levels fail to increase in response to normal stimuli

Question 21

How are the levels of phosphate reduced in renal bone disease?

Answer 21

Phosphate is excreted by the renal tubules so reduced renal function leads to reduced phosphate excretion
Increased phosphate levels in the blood - phosphate effects how calcium is handled in the body

Question 22

How are the levels of vitamin D affected in renal bone disease?

Answer 22

cholecalciferol must be activated in the liver and kidney
Reduced renal function => reduced activation of vitamin D
Reduced calcium absorption in the kidneys
Reduced GI calcium absorption

Question 23

How are the levels of calcium affected in renal bone disease?

Answer 23

Reduced calcium absorption in the kidneys
Reduced GI calcium absorption
PTH responsible for calcium homeostasis and PTH becomes elevated in repose to low serum calcium and low activated vitamin D

Question 24

How does PTH maintain homeostasis?

Answer 24

Reducing urinary clearance of calcium
increasing urinary clearance of phosphate
increasing vitamin D synthesis and activation
Increasing bone turnover to release calcium and phosphate stores from bones

when Ca+ and vit D levels are increased these act as negative feedback to the parathyroid gland to reduce PTH secretion and this feedback loop is lost in CKD

Question 25

What does secondary hyperparathyroidism lead to?

Answer 25

Further release of PTH
Increased hyperplasia of the parathyroid glands
Reduced vit D receptors on the gland
Reduced sensitivity of the parathyroid gland to serum calcium levels
accelerated bone turnover leading to elevated calcium levels

Question 26

What does high levels of PTH cause?

Answer 26

Increased activity of osteoblasts and osteoclasts
High bone turnover
Weakened bone architecture and fibrotic bone changes (osteitis fibrosa)
Mixed renal osteodystrophy
Pathological fractures, micro fractures, bone and muscle pain

Question 27

What does low vitamin D cause?

Answer 27

Reduced activity of osteoblasts and osteoclasts
Low bone turnover
Defective bone mineralisation leading to immature bone cells (osteomalacia)