Etiology

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Pathophysiology

Prerenal

• Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction) → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na⁺, H₂O → increased Urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H₂O and urea
• Creatinine is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.

Intrinsic

• Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes (e.g., Na⁺), water, and/or urea (depending on the location of injury along the tubular system) → increased Na⁺ and H₂O in the urine → decreased Urine osmolality

Postrenal

Four phases of AKI

1. Initiating event (kidney injury)
2. Oliguric or anuric phase (maintenance phase)
   • 1–3 weeks
3. Polyuric/diuretic phase
   • ∼ 2 weeks
   • Glomerular filtration returns to normal, which increases urine production (polyuria), while tubular reabsorption remains disturbed.
     • Generally, the glomeruli recover faster than the tubular system
   • Complications: loss of electrolytes and water (dehydration, hyponatremia, and hypokalemia)
4. Recovery phase

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Clinical features

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Subtypes and variants

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Acute tubular necrosis

• Epidemiology: causes ∼ 85% of intrinsic AKIs
• Location
  • The straight segment of the proximal tubule and the straight segment of the distal tubule (i.e., the thick ascending limb) are particularly susceptible to ischemic damage.
    • They are in medulla and they have high metabolic activity.
  • The convoluted segment of the proximal tubule is particularly susceptible to damage from toxins.
    • First encounters toxins
• Etiology
  • Ischemic: Injury occurs secondary to decreased renal blood flow.
    • Severe hypotension, especially in the context of shock: hypovolemic (e.g., hemorrhage, severe dehydration), septic, cardiogenic (e.g., heart failure), or neurogenic shock
    • Cholesterol embolism (atheroemboli)
  • Toxic: Injury occurs directly due to nephrotoxic substances.
    • Contrast-induced nephropathy
    • Medication: aminoglycosides, cisplatin, amphotericin, lead, ethylene glycol
    • Pigment nephropathy
      • Myoglobinuria due to rhabdomyolysis (crush syndrome)
      • Hemoglobinuria associated with hemolysis
• Diagnostic

Acute tubular necrosis vs Renal papillary necrosis

• ATN: Oliguria
  • Causes: ischemic or toxic
• RPN: Flank pain, hematuria
  • Causes: sickle cell disease, NSAIDs

Diagnostics

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Urine sediment

• Prerenal: hyaline casts due to concentrated urine in the setting of low renal perfusion
• Intrinsic: renal tubular epithelial cells or granular, muddy brown, or pigmented casts
• Postrenal: none

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Treatment

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