Acute kidney injury

Question 1

How can renal disease be classified?

Answer 1

Either by the cause (and location) or the reversibility

Question 2

State the causes of pre renal failure.

Answer 2

The main cause of pre renal failure is when there is a reduced renal perfusion (lack of blood supply) to the kidney.
This can be caused by:
Hypovolemia
Reduced cardiac output
Infection
Liver
Medications

Question 3

What are some of the potential causes of hypovolemia?

Answer 3

Haemorrhage, severe burns, dehydration

Question 4

In what conditions would you expect to see a reduced cardiac output?

Answer 4

In heart failure (chronically) or in a myocardial infarction (acutely, but then can develop into heart failure) or pulmonary embolism.

Question 5

What specific liver conditions can cause reduced renal perfusion?

Answer 5

Cirrhosis of the liver, reduces the blood supply that can enter through the liver, resulting in a backlog (portal hypertension) and reduces onward perfusion to the kidneys.

Question 6

What are some of the medications that affect kidney function and renal perfusion?

Answer 6

Laxative abuse in addition to drugs that have a side effect of nausea and vomiting and this could put the patient (especially elderly patients) into a hypovolemic state therefore causing reduced renal perfusion.

Nephrotoxic drugs such as Ciclosporin and Tacrolimus.

Diuretics promote natriuresis, increasing water excretion which can reduce renal perfusion due to hypotensive effect.

Most commonly NSAIDs and ACEI due to their effects on the arterioles, affecting the hydrostatic pressure.

Question 7

Explain the importance of hydrostatic pressure in the glomerulus and how it is maintained.

Answer 7

Hydrostatic pressure is the forced exerted by the systemic blood pressure within the glomerulus (bundle of capillaries). This pressure maintains the glomerular filtration rate as it pushes the small molecules within the blood across the glomerular filtration membrane into the Bowman’s capsule.

As mentioned the hydrostatic pressure relates to the systemic blood pressure with the glomerulus, the pressure which is controlled by the afferent (brings in the blood) and efferent arteriole (exits the blood). To maintain a sufficient blood pressure afferent arterioles dilate by prostaglandin, PGE2 and Prostacyclin PGI2 ensuring a sufficient perfusion of blood into the glomerulus and the efferent arterioles constrict by angiotensin II, reducing the blood supply out of the glomerulus.

Question 8

Explain how NSAIDs reduces the GFR.

Answer 8

NSAIDS inhibit the production of both prostaglandin PGE2 and prostacyclin PGI2 meaning that under a hypovolemic state in order to increase renal perfusion they are no longer able to act on their respective receptors on the afferent arteriole causing a vasodilatory effect, increasing the renal perfusion. Therefore NSAIDs indirectly exert an overall vasoconstriction effect on the afferent arteriole reducing blood supply into the kidney, reducing the systemic blood pressure within the glomerulus, reducing the hydrostatic pressure and therefore reducing the glomerular filtration rate and potentially causing kidney injury due to reduced perfusion.

Question 9

Explain how ACEI reduce the GFR.

Answer 9

ACEI inhibits angiotensin converting enzyme which converts angiotensin I to its active form angiotensin II. This means angiotensin II is no longer able to bind to the efferent arteriole AT1 receptors inducing a vasoconstrictor effect, to maintain the hydrostatic pressure within the glomerulus.
This means ACEI exert an overall vasodilatory effect on the efferent arteriole, increasing the blood flow out of the kidney, reducing the blood pressure within the glomerulus and the hydrostatic pressure resulting in a correlating reduction in the glomerular filtration rate.

Question 10

Explain why ACE inhibitors are used in CKD but not AKI despite GFR potentially being the same.

Answer 10

Whilst in AKI defined by a sudden decline in renal function usually due to being in a hypovolemic state, ACEI can exacerbate this causing a worsening renal function due to causing reduced efferent vasoconstriction, decreasing the hydrostatic pressure further and decreasing the GFR, and therefore it is held in AKI until renal function resolves or as part of the sick day rules.

However in chronic kidney disease, ACE inhibitors have a long-term reno-protective effect. Sustained hypertension associated with vasoconstriction can lead to efferent arteriole stenosis and loss of nephron function. Loss in nephron function can lead to hyperfiltration to other nephrons, causing stenosis. Therefore reducing hydrostatic pressure long-term preserves renal function but only when renal perfusion is adequate.

Question 11

What is intrinsic renal failure?

Answer 11

When damage has occurred to the renal tissue, often secondary to pre-renal failure and a prolonged reduced renal perfusion.

Question 12

State the causes of intrinsic renal failure.

Answer 12

Glomerular
Tubular
Renovascular
Infection
Nephrotoxicity
Metabolic - hypercalcaemia and hyperuricaemia
Congenital

Question 13

Which conditions can cause glomerular intrinsic renal failure?

Answer 13

Diabetic neuropathy - prolonged hyperglycaemia leads to the production of reactive oxygen species, causing inflammation, fibrosis and increased vascular permeability (detected by albumin within the urine).

Glomerulonephritis- kidneys become prone to build up on inflammatory mediators as they are responsible for their secretion, reduced GFR can cause their build up leading to intrinsic damage, can lead to haematuria. Any inflammation can lead to afferent arteriole vasoconstriction.

Question 14

Which conditions can cause tubular intrinsic renal failure?

Answer 14

Interstitial nephritis - kidneys become prone to build up on inflammatory mediators as they are responsible for their secretion, reduced GFR can cause their build up leading to intrinsic damage, can lead to haematuria. Any inflammation can lead to afferent arteriole vasoconstriction.

Acute tubular necrosis - necrosis of the kidney tissue due to prolonged reduced renal perfusion. This is an example of a pre-renal cause resulting in intrisnic kidney damage.

Question 15

What are some of the reno-vascular causes of intrinsic damage?

Answer 15

Damage to the endothelium, inflammation can lead to coagulation resulting in necrosis and/or vasoconstriction of the afferent arteriole (pre-renal cause) further limiting renal perfusion.

Question 16

What types of renal failure do NSAIDs cause?

Answer 16

Normally NSAIDs cause pre-renal failure, due to their vasoconstriction effects of the afferent arteriole reducing the renal perfusion and hydrostatic pressure within the glomerulus.
However sometimes the vasoconstrictor effects indirectly exerted by NSAIDs (due to inhibiting prostaglandin synthesis) can be powerful enough to cause acute interstitial nephritis which is intrinsic renal failure.

Question 17

Aside from NSAIDs which other nephrotoxic drugs are capable of causing intrinsic renal failure?

Answer 17

Hypersensitivity - unpredictable reactions arising from inter-person variability

Glomerulonephritis can be caused by Phenytoin and Penicillin
Interstitial damage - Penicillin, Cephalosporin, Allopurinol and Azathioprine

Directly toxic - predictable
Aminoglycosides (Vancomycin and Gentamicin), Amphotericin, Ciclosporin

Question 18

What is the appropriate management for administrating nephrotoxic drugs?

Answer 18

In drugs that have the potential to cause hypersensivity reactions, monitor the patient closely for any signs of renal toxicity.

In drugs that are known nephrotoxic, dosing is based upon renal function and certain drugs are contra-indicated in CKD. Renal function needs to be monitored closely due to causing renal impairment within one dose in addition to therapeutic drug levels - especially for antibiotics.

Question 19

What does post-renal failure arise from?

Answer 19

Obstruction to the urinary flow which causes a back pressure within the kidney. High pressure can lead to damage and scarring.

Question 20

State the causes of urinary flow obstruction.

Answer 20

Kidney stones blocking the ureter
Tumour or strictures
Nephrotoxic drugs such as cytotoxic (MTX) or high dose sulfonamides which can cause deposition within the urinary tract leading to back flow
Outside the urinary tract - enlarged prostate (BPH) or prostatitis causing pressure on the urethra blocking the flow. This can also be caused by ovarian tumours.

Question 21

What is the appropriate management for suspected post-renal acutely failure?

Answer 21

Ultrasounds to detect acute urinary retention and a temporary catheter may be inserted.

Question 22

What are the different categories for reversibility of renal function?

Answer 22

Impaired renal function can either be categorised into:

-An acute kidney injury
-Chronic kidney disease
-End stage renal failure

Can also have a AKI on CKD, a sudden decline in renal function in a patient with established chronic kidney disease

Question 23

Define an acute kidney injury.

Answer 23

Can be defined as a rapid decline to renal function, which will continue to decline if not treated appropriately and result in multiple organ damage and death.
Up to 90% if left untreated.

However if treated appropriately there can be a complete or partial reversal of renal function.

Question 24

What is the mortality associated with AKIs each year?

Answer 24

Up to 100,000 deaths each year within the UK, 30% are deemed as preventable

Question 25

What is the prevalence of AKI within the UK?

Answer 25

400-600 patients per million of the population experience an AKI each year

Up to 200 patients per million of the population per year require AKI dialysis

Question 26

Describe how AKIs can be diagnosed.

Answer 26

A positive AKI diagnosis is:
A rise is serum creatinine of greater than or equal to 26.5 micromol/L within 48 hours or
Creatinine greater than 1.5x the baseline within the last 7 days

Or more commonly used:
A urine output of less than 0.5mL/kg/hr for 6 hours

Question 27

What is the sign of AKI used in hospital documents?

Answer 27

Exclamation mark within a red triangle

Question 28

Describe the staging of AKI.

Answer 28

Stage 1 - 1.5 to 1.9x baseline creatinine
Stage 2 - 2.0 to 2.9x baseline creatinine
Stage 3 - 3.0x or more baseline creatinine

Question 29

What are some of the risk factors for AKI development?

Answer 29

Having had a previous AKI
Chronic kidney disease
Diabetes - both the condition and medication used to manage it
Age - over 65s natural decline in renal function, in addition to being prone to dehydration and presence of co-morbidities (and medications)
Chronic cardiac failure or HF - can influence and worsen renal perfusion, damaging to the renal vasculature compromising blood flow
Peripheral vascular disease - narrowing of blood vessels due to arteriosclerosis or atherosclerosis
Liver cirrhosis - reducing renal perfusion

Question 30

Which type of AKI is most common?

Answer 30

The sudden but reversible decline in renal function is usually a pre-renal AKI due to the patient being in the hypovolemic state.

This can be caused by infection, sepsis, dehydration and present with hypotension.

Question 31

What is the ‘triple whammy’ of medication relating to AKIs?

Answer 31

This refers to the concurrent use of ACEI or ARBs, NSAIDS and Diuretics. When any of these medicines are prescribed together the patient’s risk of acute kidney injury (AKI) is increased, and when all three are prescribed at once the risk is greatest.

Question 32

What is the appropriate management for a patient taking 2/3 or all 3 of the triple whammy medications?

Answer 32

In patient’s already taking ACEI/ARBs and a diuretics, discourage OTC use and see if there is an alternative available such as Paracetamol.
If NSAIDs do have to be used ensuring they are used at the lowest dose for the shortest duration. Try to avoid using them for long-term conditions.
Identifying patients that are high risk and avoiding nephrotoxic in these groups, for example NSAIDs in the elderly, co-prescribe PPI if needed.

If 2/3 or 3/3 are being taken:
Monitor and review frequently especially medications known to exacerbate, end date associated with NSAID use
Monitoring renal function in those raking high risk drugs with high risk co-morbidities
Educating patient’s on the sick day rules to mange high risk medications
Avoid inadvertently taking additional NSAIDs - educate on brand names and types
Establishing a high fluid intake

Question 33

What are the sick day rules?

Answer 33

During times of illness and infection, the following medicines should be stopped due to increased risk of dehydration and AKI and restarted 24-48 hours after feeling better.
The following medications include:
SGLT-2 inhibitors (euglycemic ketoacidosis)
ACE inhibitors (reduced efferent vasoconstriction)
Diuretics (volume depletion)

Metformin (lactic acidosis)
ARBs (efferent vasoconstriction)
NSAIDs (reduced afferent vasodilation)

Remember SAD MAN

Question 34

What are the first signs and symptoms of AKIs?

Answer 34

Patient usually presents firsts with signs of hypovolemia (volume depletion) this can include:
Thirst
Fluid loss
Oliguria (urine output less than 0.5 mL/kg/hour)
Reduced skin elasticity
Presenting clinically dry - dry mucosa
Tachycardic
Hypotensive
Reduced jugular venous pressure

Question 35

If an AKI is left untreated how may the patient present?

Answer 35

Patient will transition from presenting with volume depletion to volume overload, as due to the suddenly depleted GFR, over time there becomes a delayed backlog within the periphery, causing oedema.
Patient may present with swelling of the ankles (peripheral oedema)
and/or pulmonary oedema with crackles and orthopnea (breathless laying down).

Question 36

What is Step 1 of the management of AKI?

Answer 36

Identification of the cause which can be conducted through plasma and urine tests in addition to taking a thorough patient and medication history.

Question 37

Which medications need to be held/dose adjusted in AKI?

Answer 37

Medications should be held if they are known to exacerbate AKI:

This includes NSAIDS, ACEI/ARBs and diuretics, which would further reduce renal perfusion. Any medication that is known to directly or indirectly reduce renal perfusion.

Medications that are highly renally excreted should be dose reduced such as Metformin or DOACs.

These should be reinitiated post-AKI

Question 38

What is Step 2 of the management of AKI?

Answer 38

Restoring and maintaining renal function:
As pre-renal AKI are most common, patient is hypovolemic, this usually involves aggressive early fluid resuscitation to restore perfusion.
Depending on the cause this could be 0.9% NaCl or a blood transfusion if haemorrhaged

Fluid balance should be monitored during this process

Question 39

What intervention can also be used in treating AKI patients?

Answer 39

1/3 of patients are started on dialysis to maintain the renal function whilst the underlying cause is treated.

Question 40

When is dialysis most likely to be used in AKI patients?

Answer 40

For late stage CKD patients or in acute emergencies.

Acute emergencies include those with:
A rapidly rising creatinine/urea, severe hyperkalaemia or metabolic acidosis.

Question 41

What is the appropriate management for fluid overloaded patients?

Answer 41

This is when there is no issue with renal perfusion or perfusion has been restored.

First line:
Loop diuretics - IV Furosemide
1-2 grams over 24 hours with a maximum of 4mg/mL due to associated ototoxicity

In ITU- Dopamine may be used
Low dose 2 microgram/kg/min induces renal vasodilation by DA1, increasing perfusion and urine output

At higher doses however over 5mcg/kg/min this causes vasoconstriction

Monitor for dehydration closely

Question 42

What other treatments may be seen alongside fluid management?

Answer 42

Antibiotics - if there is underlying infection, dose should be closely titrated to renal function at all times and as it improves

Electrolyte correction - hyperkalaemia due to potential to cause muscle weakness and cardiac arrhythmias (ventricular fibrillation) associated with a level of over 6.5 mmol/L

Question 43

At what level should interventions be made for patient’s presenting with hyperkalaemia?

Answer 43

In AKI patients - a potassium level of 6 mmol/L
However in non-AKI patients - a potassium level of 6.5 mmol/L should always require intervention, may treat when lower

If over 6.0 mmol/L conduct ECG, if over 6.5 mmol/L treat immediately regardless of ECG

Question 44

What is the appropriate management for hyperkalaemia?

Answer 44

First:
IV 30mL Calcium gluconate10% (antagonises potassium at the cardiomyocyte membrane):
Administer over 10 minutes or 30 minutes if on Digoxin.
Repeat ECG, consider further dose after 5-10mins if ECG changes present

Following:
Rapid acting insulin (to stimulate the sodium-potassium transporter and drive potassium into cells):
Take pre blood glucose level
Give 10 units of Actrapid in 50mL of 50% glucose over 15-30mins
If pre blood glucose less than 7.0 mmol/L give 10% glucose at 50mL/hr for 5 hours, monitor closely and titrate rate of infusion

Consider:
Nebulised salbutamol (increases the potassium uptake into cells, reducing serum potassium):
10-20 grams nebulised