Acute Kidney Injury (AKI)

Introduction

Acute kidney injury (AKI) is a rapid and reversible loss of renal function occurring over a timespan of days to weeks. It is a common condition that affects approximately 20% of hospital patients. AKI is usually accompanied with a reduction in urine production.

In the presence of kidney disease of unknown duration, chronic kidney disease (CKD) should also be considered in the differential diagnosis, especially in the presence of features consistent with chronic disease, such as:

• Anaemia
• Small kidneys on imaging
• Hypocalcaemia and hyperphosphataemia

Diagnosis

Diagnostic criteria include the presence of any of the following:

a) Creatinine rise of 26µM or more within 48 hours

b) Creatinine level 1.5x or higher compared to baseline

c) Oliguria (output <0.5ml/kg/hr for 6 hours or longer)

Staging

Causes

Pre-renal

Refers to AKI developing as result of reduced renal perfusion. Accounts for approximately 60% of cases. Causes include:

• Dehydration
• Sepsis
• Blood loss
• Heart failure
• Vascular occlusion
• Hepatorenal syndrome

Renal

AKI developing because of intrinsic kidney damage. Accounts for approximately 35% of cases. Causes include:

• Acute tubular necrosis
• Glomerulonephritis
• Interstitial disease:
  • Drugs e.g. NSAIDs, ACEi
  • Lymphoma
  • Tumour lysis syndrome
  • Infection
• Vascular disease:
  • Vasculitis
  • Haemolytic uraemic syndrome/Thrombotic thrombocytopaenic purpura

Post-renal

AKI caused by diseases downstream of the kidney, which are mostly of an obstructive nature. Accounts for 5% of cases and causes include:

• Luminal disease:
  • Stones
  • clots
• Mural disease:
  • Cancer
  • Benign prostatic hypertrophy
• Extrinsic compression:
  • Malignancy
  • Retroperitoneal fibrosis

Risk factors

The risk of AKI is increased by the following long-term factors:

• Age above 75 years
• Chronic kidney disease (CKD)
• Diabetes mellitus
• Heart failure
• Chronic liver disease

Pathophysiology

In pre-renal disease, a reduction in renal perfusion and glomerular filtration leads to acute tubular necrosis, leading to inflammation, focal breaks in basement membrane and interstitial oedema. Similarly, renal disease leads to inflammation and similar pathological changes to pre-renal disease.

In contrast, post-renal produce damage as a result of back pressure on the kidneys. This reverses Starling forces because of the increased luminal pressure, impeding filtration.

Clinical features

AKIs can be asymptomatic and only incidentally picked up on blood tests. General symptoms and signs include:

• Oliguria/anuria
• Uraemic symptoms:
  • Nausea / vomiting
  • Anorexia
• Confusion
• Fluid retention:
  • Peripheral oedema
  • Pulmonary oedema (producing dyspnoea)

Clinical features pointing towards specific causes

• Hypotension, tachycardia: hypovolaemia
• Haematuria and proteinuria: Glomerulonephritis
• Bladder enlargement: Postrenal cause
• Muscle pain: Rhabdomyolysis
• Dyspnoea with haemoptysis: Goodpasture’s syndrome
• Retinal changes: Malignant hypertension, diabetes mellitus

Investigations

Urine tests

Urine dipstick:

• Glomerulonephritis: haematuria, proteinuria
• Urinary infection: leucocytes, nitrites

Urine analysis:

• Urinary sodium and urinary sodium are useful in differentiating pre-renal from renal causes. As intrinsic kidney function is intact in pre-renal disease, the kidneys reabsorb fluid and electrolytes appropriately. In contrast, renal disease results in inadequate reabsorption of solutes and impaired urine concentration ability. Therefore, urine analysis shows:
  • Pre-renal disease: ↑Urine osmolality, ↓Urine sodium
  • Renal disease: ↓Urine osmolality, ↑ Urine sodium

Urine microscopy:

• Dysmorphic red blood cells/casts: Glomerulonephritis
• Leucocytes: Infection
• Crystals: Drug-induced, uric acid nephropathy

Blood tests

Bloods tests check for kidney function and complications of kidney disease.

• Urea and electrolytes: check kidney function and electrolytes
• Full blood count: check for anaemia, which may suggest more long-standing kidney disease. Also check for signs f haemolysis (e.g. haemolytic uraemic syndrome, thrombotic thrombocytopaenic purpura)
• Liver function tests: nephrotic syndrome produces hypoalbuminaemia
• C-reactive protein
• Bone profile (includes calcium levels): hypocalcaemia is seen with long-standing kidney disease

Depending on clinical history, also consider:

• Creatinine kinase if suspecting rhabdomyolysis
• Blood film and immunology screen (including complement levels and immunoglobulins) if suspecting renal disease

Imaging

Consider renal ultrasound scan to assist in the diagnosis of obstructive causes.

Additionally, a chest x-ray be arranged if suspecting an infective source from the chest or pulmonary oedema.

Management

Treatment of AKIs should be directed at treating the underlying cause and managing associated complications, including:

1. Hyperkalaemia
2. Fluid overload (commonly as a result of excessive infusions)

General management advice

1) Assess fluid status through:

• Change in urine output
• Skin turgor
• Blood pressure and heart rate recordings
• Lung sounds – check for pulmonary oedema
• Peripheral oedema
• Maintain euvolaemia – record and review fluid charts
• Treat underling cause

3) Review drug chart to consider withholding and/or reducing drug doses

4) Regular monitoring of kidney function

Treating underlying cause

This should be directed at the underlying cause. Pre-renal causes are commonly due to hypovolaemia, which requires fluid resuscitation; antibiotics should be added if infection is suspected. Renal causes should be referred to nephrology for specialist advice.

Most post-renal cases can be treated by urinary catheterisation to help relieve urinary flow obstruction. If this is unsuccessful, further imaging (e.g. CT of kidneys, ureters and bladder) should be arranged and patient referred for urological advice.

Managing complications of AKI

Hyperkalaemia

Hyperkalaemia is life-threatening if serum potassium is above 6.5 mM and/or symptomatic (e.g. palpitations). ECG signs include tented T waves, wide QRS complexes, long PR interval and, in severe cases, development of ‘sine’ wave appearance.

Acute treatment for hyperkalaemia includes:

1. IV 10 mL 10% calcium gluconate or calcium gluconate: these act as cardioprotective agents that stabilise cardiac membrane potential. Note that they should be injected slowly over 5-10 minutes
2. IV insulin and glucose: drive potassium into intracellular compartments
3. Nebulised salbutamol: drive potassium into intracellular compartments

The above measures do not themselves excrete potassium but provide stabilise the patient until definitive potassium clearance occurs, be it by kidney function recovery or starting haemofiltration. If hypovolaemic, resuscitate with IV fluids (which additionally dilutes potassium), whereas hypervolaemic patients can receive loop diuretics to stimulate potassium excretion.

Pulmonary oedema

Pulmonary oedema commonly occurs in AKI as a result of excessive IV fluid resuscitation, especially in sepsis; patients are predisposed towards oedema through increased capillary permeability. Management of pulmonary oedema includes:

1. Oxygen supplementation with aim SpO2 of 94-98%
2. Diamorphine, which produces venous dilution
3. Furosemide
4. If above is unsuccessful, add IV glyceryl trinitrate infiltrate if blood pressure is >90/60 mmHg
5. If there is no response, consider admission to intensive care for urgent haemofiltration

 Uraemia

Consider haemofiltration in symptomatic cases e.g. pericarditis, seizures

Acidaemia

Treat acutely with sodium bicarbonate and consider haemofiltration in severe cases