23rd June 2023

Classification of acute kidney injury (AKI)

AKI definitions

Acute kidney injury is the term used to describe a rapid deterioration in renal function, generally over a period of hours to days. It is a common feature amongst hospital inpatients and is associated with adverse outcomes such as increased length of stay and increased mortality. It is a clinical syndrome with a separate underlying cause – identifying and managing this precipitating disorder is key to management.

Staging of acute kidney injury

Recommendations from NICE and the UK Renal Association suggest the use of the KDIGO (Kidney Disease: Improving Global Outcomes) criteria:

Pre-renal AKI

A pre-renal AKI is caused by a reduction in renal blood flow. Causes include:

• Reduced actual circulating volume:
  • Haemorrhage
  • Dehydration
  • Excess gastrointestinal or urinary losses, e.g. osmotic diuresis secondary to hyperglycaemia
  • Third-space loss of fluid, e.g. pancreatitis
  • Burns
• Reduced apparent circulating volume – may not necessarily be overall volume depletion, but effective circulating volume and, therefore, renal perfusion reduced for another reason
  • Peripheral vasodilatation e.g. sepsis
  • Reduced cardiac output
• Intrarenal haemodynamic changes
  • Non-steroidal anti-inflammatory drugs (inhibition of prostaglandin synthesis, reducing afferent artery dilatation)
  • ACE inhibitors (oppose efferent artery vasoconstriction, reducing perfusion pressure)

Intrinsic renal AKI

This encompasses disease processes which affect the renal parenchyma. Causes can be stratified by the location affected:

• Vascular
  • Large vessel disease – renal artery occlusion (e.g. cholesterol embolus, thrombosis), renovascular disease or renal vein pathology (e.g. thrombus)
  • Small vessel disease and glomerulonephritis – glomerulonephritides (see Glomerular diseases section), thrombotic microangiopathies (e.g. haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura), scleroderma, pre-eclampsia, malignant hypertension
• Tubulointerstitium
  • Acute tubular necrosis (see below), rhabdomyolysis, tumour lysis syndrome, cast nephropathy (e.g. due to myeloma), acute interstitial nephritis (e.g. drug-induced or secondary to infections), contrast nephropathy

Acute tubular necrosis (ATN)

Prolonged pre-renal AKI can lead to acute tubular necrosis; it can also be caused by intrinsic disorders, e.g. rhabdomyolysis, drugs, and contrast. The pathogenesis is complex, however centres around vascular supply to the renal tubules. Reduced blood flow results in vasoconstriction, leading to cell hypoxia; areas particularly vulnerable to this include the proximal convoluted tubule and the ascending loop of Henle. Cells die, and the resulting debris enters the tubular lumen, where it can form casts that cause obstruction. Other factors involved include backleak of filtrate through damaged tubules and injury to the vascular endothelium. Tubular structure and function can recover after some time once the blood supply has normalised; patients will frequently experience a period of polyuria before the tubules are able to concentrate urine again.

Post-renal AKI

A post-renal AKI is caused by an obstruction in the anatomy of the renal tract, preventing the free flow of urine. Resulting increased pressure on the kidneys can directly affect function, which can persist if the obstruction is not relieved in a timely manner. An impact on renal function is more likely in cases of obstruction of a single kidney or a process causing bilateral obstruction.

Common causes include:

• Prostate hypertrophy
• Haematuria causing clot retention
• Abdominal/pelvic masses
• Ureteric stones
• Neurological causes of urinary retention