28.2: Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.

Etiology and Pathophysiology of Acute Kidney Injury

1. Prerenal causes

Etiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity without causing direct kidney damage.

Common causes include:

• Hypovolemia (e.g., due to bleeding, dehydration, or severe burns)
• Decreased cardiac output, such as in heart failure or following a myocardial infarction, reduces blood flow to the kidneys, impairing filtration.
• Systemic vasodilation (e.g., due to sepsis or liver failure)
• Renal artery stenosis

Pathophysiology:

• In prerenal acute kidney injury, the kidneys remain structurally intact, but there is a marked reduction in renal blood flow, leading to a low glomerular filtration rate (GFR).
• The kidneys attempt to compensate by activating autoregulatory mechanisms, such as prostaglandin-mediated dilation of the afferent arteriole and angiotensin II-mediated constriction of the efferent arteriole, to preserve GFR. To maintain fluid balance, the kidneys enhance sodium and water reabsorption.
• However, if perfusion is not restored promptly, prolonged low blood flow can lead to ischemic injury and may evolve into intrinsic acute kidney injury, often in the form of acute tubular necrosis (ATN).

2. Intrarenal (Intrinsic) causes

Etiology: Intrarenal acute kidney injury results from direct injury to the kidney’s internal structures, affecting the glomeruli, tubules, interstitium, or vasculature.

Key causes include:

• Acute tubular necrosis (ATN) due to ischemia or nephrotoxins (e.g. certain medications or contrast agents)
• Acute interstitial nephritis (AIN), often due to drug reactions or infections
• Glomerulonephritis (GN), caused by immune-mediated damage
• Vascular diseases, such as vasculitis or malignant hypertension

Pathophysiology: The pathophysiology of intrarenal acute kidney injury depends on the specific site of injury:

• In acute tubular necrosis (ATN), ischemia or nephrotoxins damage the renal tubular epithelial cells, leading to cell death and sloughing of cells into the tubular lumen. This results in obstruction, a decreased GFR due to filtrate back-leak, and reduced urine output.
• In acute interstitial nephritis (AIN), an immune response to medications or infections causes inflammation and edema in the renal interstitium, impairing tubular function.
• In glomerulonephritis (GN), immune complexes or other factors induce inflammation and damage the glomeruli, resulting in reduced filtration, proteinuria, and hematuria.

If treated promptly, ATN is often reversible, though severe or prolonged ATN can lead to permanent damage.

3. Postrenal causes

Etiology: Postrenal acute kidney injury occurs when an obstruction impedes urine flow, causing back pressure in the urinary system.

Common causes include:

• Ureteral obstructions (e.g., kidney stones, strictures, tumors)
• Bladder outlet obstructions (e.g., benign prostatic hyperplasia or prostate cancer)
• Urethral strictures or injury
• Pathophysiology: When urine flow is blocked, pressure builds in the urinary system, increasing hydrostatic pressure in the renal tubules, which reduces GFR.
• Early in the obstruction, the kidneys may compensate for mild blockages. However, prolonged obstruction leads to renal ischemia, hydronephrosis (swelling of the kidneys due to urine accumulation), and tubular atrophy.
• Without timely intervention, this damage may become irreversible, resulting in permanent loss of kidney function.