Acute Kidney Injury

Question 1

What is acute kidney injury (AKI)?

Answer 1

This is an acute decline in renal function, leading to a rise in serum creatinine and/or a fall in urine output.
Kidney injury presents a disease spectrum from mild renal impairment to severe renal failure.

Question 2

What is AKI most commonly associated with?

Answer 2

Sepsis 
Cardiovascular collapse 
CHF 
Major surgery 
Nephrotoxins (antibiotics, IV contrast) 
Urinary outflow obstruction

Question 3

How does AKI present?

Answer 3

Flank pain 
Decreased urine output 
HTN or hypotension 
Oedema
Lethargy 
Uraemia 
It is however often asymptomatic

Question 4

What is essential for the diagnosis of AKI?

Answer 4

An acute increase in serum creatinine is essential for diagnosis. 
Fluid overload
Hyperkalaemia 
Hyperphosphataemia 
Metabolic acidosis 
Elevated  urea nitrogen

Question 5

What is the mainstay of AKI treatment?

Answer 5

Supportive care: 
Management of the underlying illness 
Correction of acid/base electrolyte and volume complications 
Removal or minimisation of nephrotoxins 
Relief of any associated obstruction

Question 6

Aetiology of AKI

Answer 6

Aetiology of AKI is generally classified into pre-renal, intrinsic and post-renal causes

Question 7

Pre-renal causes of AKI

Answer 7

Causes of reduced renal perfusion: 
Hypovolaemia 
Haemorrhage 
Sepsis 
The third spacing of fluid (such as in severe pancreatitis)
Overdiuresis 
Heart failure 
Hepatorenal syndrome 
Renovascular disease esp. with the recent addition of an ACE inhibitor to a patient with bilateral renal artery stenosis.

Question 8

Intrinsic causes of AKI

Answer 8

ATN, rapidly progressive glomerulonephritis and interstitial nephritis are the most common aetiologies. 
Vascular diseases: 
Haemolytic uraemic syndrome 
Thrombotic thrombocytopenic purpura
Scleroderma renal crisis
Atheromatous embolisation 
Thrombosis 
10% of intrinsic AKI causes are NSAIDs, ACEi, ARBs, gentamicin, vasculitis, myeloma, rhabdomyolysis and interstitial nephritis.

Question 9

Post-renal causes of AKI

Answer 9

Mechanical obstruction of the urinary outflow tract. 
Retroperitoneal fibrosis 
Lymphoma 
Tumour 
Prostate hyperplasia 
Strictures 
Renal calculi 
Ascending urinary infection (including pyelonephritis) 
Urinary retention

Question 10

Pathophysiology of AKI

Answer 10

Pre-renal azotaemia results from impaired renal perfusion and the changes seen are appropriate physiological responses.
The renal response is a lower perfusion pressure to enhance sodium and water re-absorption.
Baroreceptors in the carotid artery and aortic arch respond to lower BP with sympathetic stimulation.
This maintains glomerular filtration within a relatively narrow range.

Question 11

History in pre-renal failure

Answer 11

Excessive fluid loss from haemorrhage.
GI tract-vomiting, diarrhoea.
Sweating.
Symptoms of hypovolaemia: thirst, dizziness, tachycardia, oliguria or anuria.
Hx of sepsis, burns, GI surgery or pancreatitis.

Question 12

History in post-renal failure

Answer 12

More common in older men with prostatic obstruction.
Hx of urgency, frequency or hesitancy.
Hx of malignancy, prostatism, nephrolithiasis or previous surgery may coincide with the diagnosis of obstruction.
Obstruction caused by renal calculi or papillary necrosis typically presents with flank pain and haematuria.

Question 13

Hx in intrinsic renal disease

Answer 13

ATN subsequent to severe infection, nephrotoxic drug exposure, or major surgery.
Hx of rash, haematuria or oedema with HTN suggesting nephritic syndrome and acute glomerulonephritis or renal vasculitis.
Hx of myeloproliferative disorder such as multiple myeloma may predispose to AKI.
Hx of all current medicines should be taken to establish any exposure to potential nephrotoxins.
Pigment-induced AKI due to rhabdomyolysis should be suspected in patients presenting with muscle tenderness, seizures, drug abuse or alcohol abuse, excessive exercise or limb ischaemia (e.g. from crush injury)

Question 14

Physical examination findings in a patient with AKI

Answer 14

Hypotension, HTN, pulmonary oedema or peripheral oedema may be present.
There may be asterixis or altered mental status when uraemia is present.
Patients with fluid loss, sepsis or pancreatitis may have hypotension.
Patients with the glomerular disease typically present with HTN and oedema, proteinuria and microscopic haematuria (nephritic syndrome)
The presence of rash, petechiae or ecchymoses may suggest an underlying systemic condition such as vasculitis, thrombotic microangiopathy or glomerulonephritis.
An underlying abnormal bruit may support renovascular disease.
Patients with ATN may present after haemorrhage, sepsis, drug overdose, surgery, cardiac arrest or other conditions associated with hypotension and prolonged renal ischaemia.

Question 15

Investigations of AKI

Answer 15

Basic metabolic profile (including urea and creatinine) 
Venous blood gases
FBC 
Urinalysis and culture dipstick 
Urine chemistries 
Renal ultrasound
CXR-pulmonary oedema or cardiomegaly
ECG- arrhythmias is hyperkalaemia is present

Question 16

Differentials of AKI

Answer 16

CKD
Increased muscle mass
Drug side effect

Question 17

Risk factors of AKI

Answer 17

Advanced age > 65 
Underlying renal disease (acute or chronic) 
Malignant HTN 
DM 
Myeloproliferative disorders such as multiple myeloma 
Connective tissue disease.
Sodium-retaining states (CCF, cirrhosis, nephrotic syndrome)
Exposure to nephrotoxins (aminoglycosides, cancer therapies, NSAIDs, ACEi, ARBs and diuretics
Radiocontrast 
Trauma 
Haemorrhage 
Sepsis 
Pancreatitis 
Drug overdose 
Surgery 
Cardiac arrest 
Excessive fluid loss 
Recent vascular intervention 
Nephrolithiasis 
Oliguria

Question 18

Stages of AKI

Answer 18

There are 3 stages.
Stage 1:
Increase >26 umol/L within 48 hours or increase >1.5-1.9 * reference SCr
<0.5 ml/kg/hr for >6 consecutive hours.
Stage 2:
Increase >2-2.9* reference SCr
<0.5 ml/kg/hr for >12 consecutive hours.
Stage 3:
Increase >3* reference SCr
<0.3 ml/kg/hr for >24 consecutive hours or anuria for 12 hours.

Question 19

General management of AKI

Answer 19

Treat the underlying illness.
Intervention in the electrolyte and acid/base abnormalities and optimisation of volume status either by fluid replacement or fluid removal in patients with volume overload.
Sodium and volume restriction is generally required along with limiting potassium and phosphorus intake.
Patients with AKI shouldn’t be given potentially nephrotoxic drugs unless there is no alternative.

Question 20

Management of pre-renal failure

Answer 20

Managed with techniques to improve the haemodynamic status of the patient.
Hypovolaemia correction with crystalloid or colloid (but not HES)
Vasopressors are recommended if hypotension is severe.
Management is often difficult if renal hypoperfusion results from impaired cardiac function due to poor left ventricular systolic function.
RRT may be needed if severe acid/base electrolyte or uraemic complications are present while underlying cardiac or volume issues are treated.

Question 21

Management of intrinsic failure

Answer 21

Varies according to aetiology.
Volume overload require sodium restriction.
Volume expansion is required when co-existing pre-renal azotaemia exists.
Acute glomerulonephritis and vasculitis may also require corticosteroids, cytotoxic agents or other immune-modifying drugs.
No specific treatment for ATN aside from maintaining volume status and controlling electrolyte levels

Question 22

Management of obstructive renal failure

Answer 22

Bladder catheter placement

RRT may be required if indicated

Question 23

Indications of RRT

Answer 23

Refractory severe hyperkalaemia 
Acidosis 
Volume overload 
Uraemia
-Continuous RRT is required in haemodynamically unstable patients or those in whom aggressive ultrafiltration within the conventional 4-6 hour treatment of haemodialysis would not be tolerated.

Question 24

What are the key points in a history and examination to cover with reference to a patient with an acute kidney injury?

Answer 24

AKI risk factors

People aged 65 years or over.
A history of acute kidney injury.
Chronic kidney disease (estimated glomerular filtration rate [eGFR] less than 60mL/min/1.73m2).
Symptoms or history of urological obstruction or conditions which may lead to obstruction.
Chronic conditions such as heart failure, liver disease, and diabetes mellitus.
Neurological or cognitive impairment or disability (which may limit fluid intake because of reliance on a carer).
Sepsis.
Hypovolaemia.
Oliguria (urine output less than 0.5mL/kg/hour).
Nephrotoxic drug use within the last week (especially if hypovolaemic) — for example nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and diuretics.
Exposure to iodinated contrast agents within the past week

Question 25

Tests done in AKI

Answer 25

• CXR – look for pulmonary oedema or pneumonia
• Urine dipstick – look for dipstick blood and protein
• Urine culture (MSSU) – look for urine infection
• Renal tract USS – look for obstructed kidneys (hydronephrosis), kidney size
• Stool culture – pathogens causing diarrhea

Question 26

What is ATN?

Answer 26

This condition is usually the result of a combination of factors which have caused renal ischaemia and toxicity, e.g. hypotension and dehydration or sepsis with associated nephrotoxic drugs.

Question 27

What is the histology of the kidneys in ATN?

Answer 27

The histology of ATN does not usually show frankly necrotic cells, but sloughing of the renal tubular epithelium causing dilation and obstruction of tubules and some mild leukocyte infiltration.

Question 28

Treatment of ATN

Answer 28

Treatment is supportive, there are no specific drug treatments, and withdrawal of nephrotoxic agents or treatment of associated sepsis.

Question 29

Prognosis of ATN

Answer 29

Usually there is recovery after 2 – 3 weeks (maximum 6 weeks). There is a high mortality associated with ATN (approx 50%), but this is usually because of the associated illnesses (e.g. septic shock), age etc. Once recovered only a very small proportion of people are left with chronic kidney disease. The severity of this illness is the reason such effort is made to recognise risk factors and prevent this disease.

Question 30

Phases of ATN

Answer 30

There are 3 phases of ATN:

Oligouric phase: The kidneys produce less than 500 mls of urine per day. Patients in this phase are vulnerable to fluid overload and electrolyte imbalance especially potassium. Creatinine levels usually rise quite rapidly during this phase.

Maintenance phase: The patient is no longer oligouric and this increased urinary output helps maintain fluid and electrolyte balance. Creatinine level are usually stable or rise very slowly.

Polyuric recovery phase: In this phase the kidneys produce large quantities of dilute urine, so large in fact patients can become hypovolaemic and unwell. There are a number of causes for this phase postulated, but one explanation is that the distal tubules and collecting ducts recover last and in particular their aquaporin channels. These damaged aquaporin channels do not allow water to be reabsorbed and therefore high quantities of dilute urine are produced. Patients are also susceptible to electrolyte loss (e.g. hypokalemia) in this phase. Creatinine levels falls swiftly in this phase.

Question 31

Drugs to stop in a patient with AKI

Answer 31

Metformin
Diclofenac
ARBs
ACEI