1 Acute Kidney Injury: Causes and Pathophysiology

What causes acute kidney injury

Acute kidney injury (AKI) is a rapid decline in kidney function. Its causes are commonly grouped by mechanism: reduced blood flow to the kidneys, damage within the kidneys, or obstructed urine flow. More than one mechanism may contribute in the same patient.

Reduced kidney perfusion

In prerenal AKI, the kidneys initially have no structural injury. Filtration falls because blood flow or effective circulating volume is insufficient, and the kidneys respond by retaining sodium and water to support circulating volume. If reduced perfusion is severe or prolonged, it can progress to intrinsic tubular injury.

Common causes include:

• Volume loss: vomiting, diarrhea, bleeding, burns, or excessive diuresis.

• Reduced cardiac output: heart failure, myocardial infarction, or shock.

• Systemic vasodilation: sepsis or severe liver disease.

• Medication effects: NSAIDs can limit compensatory blood flow into the glomerulus. ACE inhibitors and ARBs can reduce pressure within the glomerulus, especially in susceptible patients.

Damage within the kidney

Intrinsic AKI results from injury to kidney tubules, interstitium, glomeruli, or blood vessels. The injury can impair filtration directly, disrupt tubular function, or do both.

Acute tubular injury is a common form and may follow prolonged ischemia or exposure to nephrotoxins. Examples include aminoglycoside antibiotics, some other medications, and muscle pigment released during rhabdomyolysis. Other causes include medication-related interstitial inflammation, glomerulonephritis, and vascular disorders.

Risk rises when kidney reserve is reduced or a patient faces multiple stresses. For example, severe illness or sepsis combined with dehydration and potentially nephrotoxic drugs can increase risk.

Obstructed urine flow

Postrenal AKI occurs when urine outflow is blocked. The obstruction raises pressure upstream in the urinary tract; pressure transmitted back toward the kidney opposes filtration and lowers the glomerular filtration rate. Prolonged obstruction can cause lasting kidney damage, whereas timely relief may allow recovery.

Causes include an enlarged prostate, urinary stones, tumors, blood clots, urethral strictures, or a blocked catheter. Obstruction usually must affect both kidneys—or the only functioning kidney—to cause a substantial decline in overall kidney function.

Risk factors and clinical reasoning

Risk increases with conditions that reduce kidney reserve or make impaired perfusion, tissue injury, or obstruction more likely. These include pre-existing kidney disease, older age, severe infection, major surgery or trauma, dehydration or bleeding, heart failure, and exposure to nephrotoxic medications. An enlarged prostate or other urinary-tract disease raises the likelihood of obstruction.

Connect a patient's history to the likely mechanism:

• Fluid loss or shock suggests reduced perfusion.

• A nephrotoxin or inflammatory kidney disease suggests intrinsic injury.

• Difficulty urinating or known urinary-tract disease suggests obstruction.

These categories guide evaluation, but they can overlap. For example, heart failure can reduce effective kidney perfusion, while an NSAID can interfere with compensatory regulation of kidney blood flow; together, these factors may contribute to a prerenal problem.

Applying the mechanisms

The mechanisms can be compared by where the problem begins and how filtration is affected:

• Prerenal: inadequate kidney perfusion lowers filtration; severe or prolonged hypoperfusion can cause tissue injury.

• Intrinsic: damage within kidney tissue affects filtration, tubular function, or both.

• Postrenal: blocked urine outflow raises upstream pressure and reduces filtration.

For example, severe diarrhea points to reduced circulating volume and a prerenal mechanism. Prolonged low perfusion can deprive tubules of oxygen and cause structural injury, turning a functional perfusion problem into intrinsic injury. A prolonged nephrotoxic medication exposure is consistent with intrinsic injury. With an enlarged prostate and urinary retention, backed-up urine raises pressure upstream and opposes filtration. An obstruction in only one ureter may not cause a major decline in overall kidney function because the unobstructed kidney may maintain overall filtration.