Acute tubular necrosis

causes ∼ 85% of intrinsic AKIs

• 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.

• The convoluted segment of the proximal tubule is particularly susceptible to damage from toxins.

• 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

  • Thromboembolism

  • Thrombotic microangiopathy

  • Cholesterol embolism (atheroemboli)

• Toxic: Injury occurs directly due to nephrotoxic substances.

  • Contrast-induced nephropathy

  • Medication: aminoglycosides, cisplatin, amphotericin, lead, ethylene glycol

  • Pigment nephropathy: an acute kidney injury that occurs as a result of the toxic effects of heme-containing pigments (e.g., hemoglobin, myoglobin) on proximal renal tubular cells (toxin-induced acute tubular necrosis)

    • Myoglobinuria due to rhabdomyolysis (crush syndrome)

    • Hemoglobinuria associated with hemolysis

  • Acute uric acid nephropathy

• Other: sepsis, infections

necrotic proximal tubular cells fall into the tubular lumen → debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure (i.e., activation of RAAS; see “Pathophysiology” above)

• Blood findings: azotemia, hyperkalemia, and metabolic acidosis

• Urinary findings

  • ↑ Fractional excretion of sodium (FENa)

  • Myoglobinuria, hemoglobinuria

• Urinary sediment

  • Muddy brown granular casts

  • Epithelial cell casts

  • Free renal tubular epithelial cells (due to denudation of the tubular basement membrane)

• After 1–3 weeks, most patients with ATN will experience tubular re-epithelialization and spontaneous full recovery is common.

• Can be lethal if AKI is severe and not managed adequately (e.g., dialysis may be required in oliguric patients with volume overload or severe hyperkalemia)

Renal infarction

Photomicrograph of a renal biopsy sample (H&E stain)

The cells of the tubules and glomeruli show clumped and highly eosinophilic cytoplasm. The nuclei of these cells are either absent or palely staining. There is debris in some tubular lumens and thrombi are visible in the capillaries on the lower right. The main outlines of the tubules and glomeruli are still intact.

Urine casts in acute tubular necrosis

Photomicrograph of urine sediment (high magnification)

Renal tubular epithelial cell casts (a) and muddy brown casts (b) were identified in this urine sample.

Both findings indicate damage of the kidneys, likely due to acute tubular necrosis.