ATN

**Definition:** Acute tubular necrosis is death of renal tubular epithelial cells, leading to acute kidney injury (AKI) of intrinsic (renal) etiology. It is the most common cause of intrinsic AKI and of AKI in hospitalized patients.

**Etiologies:** - *Ischemic:* prolonged prerenal azotemia (hypotension, shock, sepsis, hemorrhage, major surgery, hypovolemia, cardiac failure). The most susceptible sites are the proximal tubule and the thick ascending limb of the loop of Henle (medullary), because of high metabolic demand and relatively low oxygen supply. - *Nephrotoxic:* aminoglycosides (gentamicin), IV contrast, cisplatin, amphotericin B, vancomycin, heavy metals (lead, mercury), ethylene glycol (oxalate crystals), myoglobin (rhabdomyolysis), hemoglobin (hemolysis), and tumor lysis syndrome (uric acid). Nephrotoxic ATN mainly affects the proximal tubule.

**Pathophysiology:** Tubular cell injury leads to loss of the brush border, loss of polarity, and sloughing of cells into the lumen. The sloughed cells and debris form casts that obstruct the tubule and raise intratubular pressure. Backleak of filtrate across the damaged epithelium and afferent arteriolar vasoconstriction (via tubuloglomerular feedback) further reduce GFR.

**Clinical course (3 phases):** 1. *Initiation:* the insult occurs and the injury begins. 2. *Maintenance:* oliguria (may be non-oliguric), rising BUN/Cr, hyperkalemia, metabolic acidosis, volume overload, hyperphosphatemia, and hypocalcemia. It lasts about 1–2 weeks. 3. *Recovery:* tubular cells regenerate. Polyuria occurs from impaired concentrating ability and post-ATN osmotic diuresis, and it risks hypovolemia, hypokalemia, and hypomagnesemia. The basement membrane is intact, so recovery is possible.

**Diagnosis:** - Urinalysis: **muddy brown granular casts** and tubular epithelial cell casts (pathognomonic). - Urine Na >40 mEq/L. - **FeNa >2%** (FeUrea >35% if the patient is on diuretics). - Urine osmolality <350 mOsm/kg (isosthenuria, the kidney can't concentrate). - BUN:Cr ratio <15 (compared with >20 in prerenal azotemia). - Contrast-induced ATN usually causes a creatinine rise 24–48 h after exposure. It may have a low FeNa early, and it peaks at 3–5 days.

**Comparison with prerenal azotemia:** In prerenal disease the tubules are intact and avidly retain sodium and water. This gives FeNa <1%, urine osmolality >500, urine Na <20, BUN:Cr >20, and hyaline casts. It reverses quickly with fluids, whereas ATN does not.

**Management:** Remove the offending agent and treat the underlying cause. Restore euvolemia and avoid further nephrotoxins. Manage the complications: hyperkalemia, acidosis, and volume overload. Dialysis is indicated for refractory hyperkalemia, acidosis, volume overload, or uremic symptoms (**AEIOU**: Acidosis, Electrolytes, Intoxications, Overload, Uremia). Prevent contrast nephropathy with isotonic saline hydration, and use N-acetylcysteine only as an adjunct of limited proven benefit. Give IV fluids early in rhabdomyolysis.

**High-yield associations:** - Rhabdomyolysis gives a positive urine dipstick for blood without RBCs, and elevated CK. - Ethylene glycol causes calcium oxalate crystals (envelope-shaped) and an anion gap acidosis. - Histology shows tubular cell necrosis, loss of the brush border, and cast formation. The ischemic form has patchy necrosis along the nephron and a ruptured basement membrane (tubulorrhexis). The nephrotoxic form has uniform proximal tubule necrosis with an intact basement membrane. - Complications include hyperkalemia (ECG changes), uremic pericarditis, and metabolic acidosis.