Acute Kidney Injury

Question 1

What is acute kidney injury (AKI)?

Answer 1

Abrupt deterioration in renal function over hours/days with evidence of rising serum urea and creatinine and low urine output.

Usually reversible over days or weeks

Question 2

Renal causes can be divided according to site into pre-renal, renal and post renal.

What is the underlying pathology in each of the categories above and examples of each?

Answer 2

I. Pre-renal causes => reduced kidney perfusion leads to falling GFR

i. Decreased vascular volume e.g. haemorrhage, diarrhoea & vomiting, burns, pancreatitis
ii. Decreased cardiac output e.g. cardiogenic shock, MI
iii. Systemic vasodilation e.g. sepsis, drugs
iv. Renal vasoconstriction e.g. NSAIDs. ACE-i, ARB, hepatorenal syndrome

II. Renal causes:

i. Injury to glomerulus e.g. glomerulonephritis, acute tubular necrosis (prolonged renal hypo perfusion causing intrinsic renal damage)
ii. Injury to the interstitium e.g. drug reaction, infection, infiltration (e.g. sarcoid)
iii. Vessels e.g. vasculitis, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura

III. Post-renal causes

i. Within renal tract e.g. stone, renal tract malignancy, stricture, clot
ii. Extrinsic compression e.g. pelvic malignancy, prostatic hypertrophy, retroperitoneal fibrosis

Question 3

What are the commonest causes of acute kidney injury?

Answer 3

Sepsis

Major surgery

Cardiogenic shock

Other hypovolaemia

Drugs

Hepatorenal syndrome

Obstruction

Question 4

How common is AKI?

Answer 4

AKI is common
=> 18% of hospital patients
=> 50% of ICU patients

Question 5

What are the risk factors for AKI?

Answer 5

Pre-existing CKD

Age

Male

Comorbidity i.e. diabetes, cardiovascular disease, malignancy, chronic liver disease, complex surgery

Question 6

How is the severity of AKI staged?

Answer 6

AKI is classified using the 3 stage KDIGO classification based on serum creatinine and urine output.

Stage 1:

Creatinine: 1.5-1.9 x baseline or >26.5umol/L (0.3mg/dL)

Urine: <0.5mL/kg/h for 6-12h

Stage 2:

Creatinine: 2.0-2.9 x baseline

Urine: <0.5mL/kg/h for >12h

Stage 3:

Creatinine: >3.0 x baseline or renal replacement therapy

Urine: <0.3mL/kg/h for >24h or anuria for >12h

Question 7

How does KDIGO classification for AKI define AKI?

Answer 7

Rise in creatinine >26umol/L within 48h

Rise in creatinine >1.5 x baseline (i.e. before the baseline) within 7 days

Urine output <0.5mL/kg/h for >6 consecutive hours

Question 8

What is the pathophysiology underlying pre-renal AKI?

Answer 8

Falling renal blood flow => falling GFR due to circulation changes or infrarenal vasomotor changes

Question 9

What are the causes of hypovolaemia (pre-renal AK)?

Answer 9

Dehydration

Reduced intake i.e. nil by mouth, confusion

Gut losses i.e. vomiting, nasogastric tube loses, diarrhoea

Renal losses i.e. diuretics, hyperglycaemia

Haemorrhage

Burns, sweating

Third space losses i.e. pancreatitis, peritonitis, bowel obstruction

Systemic vasodilation (septic shock, cirrhosis)

Cardiac failure or shock (MI, arrhythmias, cardiomyopathy, tamponade)

Question 10

NORMAL PHYSIOLOGY

Normal: Kidney maintains GFR close to normal despite variation in perfusion due to autoregulation (i.e. nitric oxide, prostaglandins and angiotensin)

Stimulus:

Reduced renal perfusion => reduced transglomerular pressure and GFR

Response:

Intrarenal activation of renin-angiotensin system

=>efferent arteriolar vasoconstriction

=> increases transglomerular pressure

=> restores GFR

Answer 10

INFO CARD

Question 11

Autoregulation fail => fall in GFR => AKI

Reduced blood flow => parenchymal injury

If renal perfusion corrected early = AKI resolved

Answer 11

INFO CARD

Question 12

Why does urine specific gravity or osmolality rise in AKI?

Answer 12

Because solutes are concentrated into smaller urine volume

Fall in urine volume is due to the kidney retaining fluid to try and improve renal blood flow

Urine sodium is also low because salt is retained to help retain fluid

Question 13

What is the management of pre-renal AKI?

Answer 13

Crystalloid fluid resuscitation

*Normal saline can lead to hyperchloraemic acidosis.

Question 14

Where can obstruction occur in post-renal AKI?

Answer 14

Obstruction anywhere between calyces to the external urethral orifice in the urinary tract

Commonly, its bladder outflow obstruction i.e. BPH or bilateral ureteric obstruction i.e. stones or tumours

*Any unexplained AKI => ultrasound to exclude obstruction because once relieved, renal function returns to normal

Question 15

What is the most common form of AKI?

Answer 15

Renal parenchymal AKI affecting 80-90% of AKI patients

Question 16

What is the most common cause of renal parenchymal AKI?

Answer 16

Acute tubular necrosis (ATN)

Any cause of pre-renal if prolonged to the point of autoregulation failure => ischaemic ATN

ATN can also result from direct tubular toxins

Question 17

What causes acute tubular necrosis?

Answer 17

Sustained under-perfusion and reduced renal blood flow of renal tubules => tubular cell death

Nephrotoxins => direct injury and cell death in renal tubules

Question 18

What is the pathology following acute tubular necrosis?

Answer 18

Reduced renal blood flow

=> reduced GFR as glomeruli contract through afferent arteriolar spasms

=> filtrate leaks backward toward the glomerulus

=> tubular obstruction

Question 19

How is pre-renal diagnosed?

Answer 19

Mostly a clinical diagnosis based on clinical examination and assessing the volume status

=> large palpable bladder suggests longstanding outflow obstruction

=> draining large urine volumes after inserting a urethral catheter

=> ultrasound of the kidneys and bladder

Question 20

What investigations are carried out in AKI?

Answer 20

Urinalysis: red blood cells indicative of glomerulonephritis

Blood tests: serum urea, creatinine, electrolytes, calcium, phosphate, albumin, alkaline phosphatase and urate concentration.

Coagulation, blood cultures and nephrotic drug blood level measurements.

Urinary & plasma biomarkers i.e. kidney injury molecule 1, insulin like growth factor binding protein 7, tissue inhibitor of metalloproteinases-2 rise within a few hours of AKI

Ultrasound is key: renal size (measured pole-pole length) and echogenicity (increased in scarring)
=> small scarred kidney suggests long term insult

Question 21

What are the complications of AKI?

Answer 21

Hyperkalaemia

Pulmonary oedema

Sepsis

Question 22

How do you manage hyperkalaemia as a result of AKI?

Answer 22

Hyperkalaemia can be life-threatening => cardiac dysrhythmias i.e. ventricular fibrillation

Treatment:
IV sodium bicarbonate reduces potassium by correcting acidosis
=> should not be used in volume overloaded patients as can trigger/exacerbate pulmonary oedema

Question 23

How do you manage pulmonary oedema as a result of AKI?

Answer 23

IV furosemide diuresis

Dialysis

Haemofiltration

Question 24

How do you manage sepsis as a result of AKI?

Answer 24

Blood cultures + septic screen + U&E

Urine output - monitor hourly + urea

Fluid resuscitation

Antibiotics IV - avoid nephrotoxic antibiotics

Lactacte - ABG

Oxygen - to correct hypoxia

Question 25

How should fluid and nutrition be managed in an AKI patient?

Answer 25

Fluid: Daily assessment x2

Bolus crystalloid fluid 250-500mL in 15 mins until volume replete
*if 2L given without response, seek help

Once patient is euvolaemic, daily fluid intake = urine output

Nutrition: salt and potassium restriction

Question 26

When may renal replacement therapy be indicated?

Answer 26

Main indication for blood purification and/or fluid removal are:

i. Symptomatic uraemia (including pericarditis or tamponade)
ii. Hyperkalaemia not controlled conservatively
iii. Pulmonary oedema not controlled by diuresis
iv. Severe acidosis
v. to remove nephrotoxic drugs i.e. gentamicin, lithium, severe aspirin overdose

Question 27

What types of renal replacement therapy may be used in AKI?

Answer 27

1. Haemodiafiltration (intermittent haemodialysis)
2. Continuous venovenous haemofiltration (CVVHF)
3. Peritoneal dialysis

Question 28

How does continuous venovenous haemofiltration (CVVHF) work to treat AKI?

Answer 28

CVVHF achieves blood flow using a blood pump to draw and return blood from the lumen of dual-lumen catheter placed in the jugular, subclavian or femoral vein.

Ultrafiltrate (i.e. plasma) is continuously removed from the patient (at rates of 1000mL/h), combined with simultaneous infusion of replacement solution

Question 29

Peritoneal dialysis is used in resource poor countries - it has low efficiency (removes fluid slowly).

Answer 29

INFO CARD

Question 30

What general measures are taken in AKI?

Answer 30

Infection control

Physiotherapy

Fluid balance (intake and urine output) => key to recovery ; consider urinary catheter + hourly urine output

Daily measurements of weight esp in patients receiving fluid (prevent fluid overload)

Daily measurements of lying and standing BP

Medication review - stop nephrotoxin meds => diuretics only in symptomatic fluid overload, otherwise not at all, esp not k+ sparing diuretics

Obs every 4 hours

Question 31

What are the ECG changes seen in AKI?

Answer 31

Hyperkalaemia:

Tall tented T waves

Increased PR interval

Small/absent p wave

Widened QRS complex

Question 32

Treat K+ >6.5mmol/L or any with ECG changes

Do ECG for all k+ >6.0mmol/L)

How do you treat hyperkalaemia ?

Answer 32

1. Give 10ml of 10% calcium chloride or 30ml of 10% calcium gluconate IV via big vein over 5-10 mins => cardioprotective but doesn’t reduce K+ levels
2. IV insulin in 25g glucose => insulin stimulates intracellular uptake of K+, lowering serum K+.
   Monitor hourly for hypoglycaemia
3. Salbutamol => intracellular K+ shift but high dose required and tachycardia can limit the use
4. Definitive treatment = K+ removal via renal replacement therapy