S10) Acute Kidney Injury

Question 1

What is acute kidney injury?

Answer 1

• AKI is a clinical syndrome wherein there is an abrupt decline in actual GFR (days to weeks)
• This disrupts homeostasis (ECF volume, electrolyte and acid-base) and leads to an accumulation of nitrogenous waste products

Question 2

In terms of laboratory findings, provide three definitions of AKI

Answer 2

• Increase in serum creatinine by ≥ 26.5 μmol/L within 48 hours
• Increase in serum creatinine by ≥1.5 times baseline within 7 days
• Urine volume <0.5 ml/kg/h for 6 hours

Question 3

Define Stage 1 AKI in terms of serum creatinine and urine output

Answer 3

• Serum Cr criteria: ↑ Cr ≥ 150-200% from baseline
• Urine output criteria: <0.5 mL/kg/hr for >6 h

Question 4

Define Stage 2 AKI in terms of serum creatinine and urine output

Answer 4

• Serum Cr criteria: ↑ Cr > 200-300% from baseline
• Urine output criteria: <0.5 mL/kg/h for >12 h

Question 5

Define Stage 3 AKI in terms of serum creatinine and urine output

Answer 5

• Serum Cr criteria: ↑ Cr >300% from baseline or initiated on RRT
• Urine output criteria: <0.3 mL/kg/h for 24 h or anuria for 12 h

Question 6

Identify the three causes of AKI

Answer 6

• Pre-renal failure (volume responsive)
• Intrinsic renal failure
• Post-renal failure

Question 7

Describe the epidemiology of AKI in high income countries in terms of:

• Typical patients
• Location
• Causes
• Treatment

Answer 7

• Patients: older people
• Location: hospital-acquired AKI
• Causes: dehydration and hypotension
• Treatment: dialysis withheld most commonly due to futility

Question 8

Describe the epidemiology of AKI in low income countries in terms of:

• Typical patients
• Location
• Causes
• Treatment

Answer 8

• Patients: younger people (often children)
• Location: community-acquired AKI
• Causes: dehydration, hypotension, obstetric causes, snake and insect bites
• Treatment: dialysis withheld due to lack of resources

Question 9

In 6 steps, outline the pathophysiology of pre-renal AKI

Answer 9

⇒ Decreased renal blood flow

⇒ Reduced actual GFR

⇒ Kidneys work hard to restore blood flow (no cell damage)

⇒ Reabsorb Na⁺ & H₂O (aldosterone, ADH release)

⇒ If mild hypoperfusion, autoregulation preserves renal blood flow

⇒ If overwhelmed compensatory responses, AKI occurs

Question 10

Explain how prescription drugs can affect renal perfusion

Answer 10

• NSAIDS and ACEi can override intrinsic autoregulatory mechanisms
• Disease of the afferent arteriole (BP, DM) can result in too great or too little a response to these stimuli

Question 11

Describe the causes of pre-renal AKI in terms of:

• Reduced effect arterial blood volume
• Impaired renal autoregulation

Answer 11

• Reduced effective arterial blood volume:

I. Hypovolaemia

II. Systemic vasodilation – sepsis, cirrhosis, anaphylaxis

III. Cardiac failure

- Impaired renal autoregulation:

I. Pre-glomerular vasoconstriction – sepsis, NSAIDs

II. Post-glomerular vasodilatation – ACEi, ARBs

Question 12

Acute tubular necrosis is volume unresponsive AKI.

Identify three of its causes

Answer 12

• Ischaemia (depletion of cellular ATP)
• Nephrotoxins
• Sepsis

Question 13

Describe the pathophysiology of ATN

Answer 13

⇒ Death of tubular epithelial cells

⇒ Damaged cells cannot reabsorb / expel excessive H₂O efficiently

⇒ Aggressive fluid resuscitation risks fluid overload

Question 14

Describe the course of renal blood flow

Answer 14

Question 15

Identify the sites of tubular injury in ATN

Answer 15

Question 16

Compare and contrast the urinary biochemistry of Pre-renal AKI and ATN in terms of:

• Specific gravity
• Osmolality
• Urinary Na⁺

Answer 16

Question 17

ATN is much more likely if there is reduced perfusion and a nephrotoxin.

What do nephrotoxins do?

Answer 17

Nephrotoxins damage the epithelial cells lining the tubules and cause cell death

Question 18

Nephrotoxins can be endogenous or exogenous.

Identify some examples of each

Answer 18

Question 19

What is rhabdomyolysis?

Answer 19

• Rhabdomyolysis is a serious syndrome due to a direct or indirect muscle injury e.g. crush injury
• Muscle necrosis cases releases of myoglobin into the bloodstream

Question 20

When is rhabdomyolysis likely to occur?

Answer 20

• AKI in wars / natural disasters (earthquakes)
• Drug users (unconscious so don’t move)
• Elderly (fall & can’t get up)

Question 21

Explain the association of rhabdomyolysis with AKI

Answer 21

• Released myoglobin is filtered at the glomerulus and toxic to tubule cells
• Released myoglobin can also cause renal obstruction

Question 22

What is myoglobinuria and how does it present?

Answer 22

Myoglobinuria is the presence of myoglobin in the urine usually associated with rhabdomyolysis or muscle destruction

Question 23

Besides ATN, identify two other intrinsic renal causes of AKI

Answer 23

• Thrombotic microangiopathy
• Acute (tubule)-interstitial nephritis

Question 24

Identify 4 clinical conditions which present with thrombotic microangiopathy

Answer 24

• Haemolytic uraemic syndrome
• Malignant hypertension
• Scleroderma
• Pre-eclampsia

Question 25

In 5 steps, explain how thrombotic microangiopathy leads to microangiopathic haemolytic anaemia

Answer 25

⇒ Endothelial damage ⇒ Platelet thrombi ⇒ Partial obstruction of small arteries ⇒ Destruction of RBC’s ⇒ Microangiopathic haemolytic anaemia occurs

Question 26

Identify and describe the two causative mechanisms of acute interstitial nephritis

Answer 26

- **Toxin induced:** antibiotics, NSAID’s, PPI's - **Infections**: due to inflammatory response (not direct effect of infection)

Question 27

Post-renal failure accounts for 5 - 10% of AKI cases. How does it occur?

Answer 27

- Occurs commonly in elderly - Obstruction must block both kidneys or a single functioning kidney

Question 28

Describe the pathophysiology of post-renal AKI

Answer 28

⇒ Obstruction with continuous urine production ⇒ Rise in intraluminal pressure ⇒ Dilatation of renal pelvis (hydronephrosis) ⇒ Decrease in renal function

Question 29

Identify and describe the three different causes of post-renal AKI

Answer 29

- **Within the lumen** (kidney, ureter, bladder) – stones, blood clot, tumours - **Within the wall** (usually cause CKD rather than AKI) – congenital megaureter, post-TB stricture - **Pressure from outside** – enlarged prostate, tumour, aortic aneurysm

Question 30

Identify 5 clinical signs in serum biochemistry which are indicative of AKI

Answer 30

- Metabolic acidosis - Hyperkalaemia - Hyponatraemia - Hypocalcaemia - Hyperphosphataemia

Question 31

In 3 steps, describe how metabolic acidosis occurs in AKI

Answer 31

⇒ Reduction in **GFR** ⇒ Impaired reabsorption & regeneration of **HCO₃**^- ⇒ Impaired **acid** excretion

Question 32

Identify and describe 4 causes of hyperkalaemia

Answer 32

- **Excessive intake** - **Movement out of cells** (acidosis / tissue damage) - **Reduced urine loss** (reduced GFR, reduce distal deliver of Na+, reduced secretion) - **Drugs** (ACE-Inhibitors, spironolactone, NSAIDs, trimethoprim, amiloride)

Question 33

Can cause life-threatening cardiac arrhythmias. Identify 5 clinical signs on an ECG that indicate hyperkalaemia

Answer 33

- Tall T waves - Small/absent P waves - Increased P-R interval - Wide QRS complex - Asystole

Question 34

Identify and describe the 5 investigations used for AKI

Answer 34

- Urinalysis (blood, protein, leucocytes) - Urine microscopy - CXR (fluid overload ± infection) - Ultrasound scan (only for obstruction – within 24 hours) - Kidney biopsy (systemic inflammatory symptoms/ igns)

Question 35

In terms of volume overload and hyperkalaemia, outline the management of AKI

Answer 35

- **Volume overload** – restrict dietary Na⁺ / water \< 1L/day - **Hyperkalaemia** – calcium gluconate, restrict dietary K⁺, stop K⁺-sparing diuretics, ACEi, ARB

Question 36

What are the 5 indications for dialysis?

Answer 36

- **Hyperkalaemia** (refractory to treatment) - **Fluid overload** (refractory to diuretics) - **Metabolic acidosis** (NaHCO₃^- not appropriate) - Signs of **uraemia** (pericarditis, reduced consciousness) - Dialysable **nephrotoxin** *e.g. aspirin overdose, ethylene glycol*

Question 37

How can one prevent AKI?

Answer 37

- Identify risk factors - Monitor ‘at risk’ patients closely - Ensure adequate hydration - Avoid nephrotoxins - Detect early and identify cause

Question 38

Identify 5 risk factors for AKI in terms of susceptibility

Answer 38

- Advanced age - CKD - Heart disease - Liver disease - Diabetes Mellitus

Question 39

Identify 5 risk factors for AKI in terms of exposure

Answer 39

- Dehydration - Sepsis - Burns / trauma - Cardiac surgery - Nephrotoxins (NSAIDS, ACE-I, ARB)