Acute Tubular Necrosis (ATN)
Most common cause of intrinsic AKI; tubular epithelial injury from ischemia or nephrotoxins.
Also known as: ATN, acute tubular necrosis, ischemic ATN, nephrotoxic ATN
Overview
Intrinsic AKI characterized by injury and necrosis of renal tubular epithelial cells, most often from ischemic insult (prolonged hypoperfusion) or direct nephrotoxic exposure. The most common cause of hospital-acquired AKI.
Epidemiology
Accounts for ~50% of hospital-acquired AKI and ~75% of AKI in critically ill patients. Mortality 40-60% in ICU patients requiring RRT.
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Risk factors
- Ischemic: sepsis, hemorrhage, prolonged hypotension, cardiac/aortic surgery
- Nephrotoxic medications: aminoglycosides (gentamicin, tobramycin, amikacin), vancomycin, amphotericin B, cisplatin, foscarnet
- Iodinated contrast (especially CKD, diabetes, dehydration)
- Endogenous toxins: myoglobin (rhabdomyolysis), hemoglobin (hemolysis), uric acid (tumor lysis), light chains (myeloma)
- Underlying CKD, advanced age, volume depletion
Pathophysiology
Ischemic or toxic injury depletes tubular ATP, disrupts apical brush borders, and causes epithelial cell death and desquamation. Sloughed cells obstruct the tubular lumen → backleak of filtrate, tubuloglomerular feedback, and reduced GFR. Three phases: initiation (hours-days), maintenance (days-weeks of established oliguric AKI), and recovery (polyuric phase as tubules regenerate).
Clinical presentation
Symptoms
- Often asymptomatic AKI discovered on labs in ICU or postoperative setting
- Oliguria or anuria common; nonoliguric ATN in 30-50% (better prognosis)
- Symptoms of underlying cause: sepsis, shock, recent surgery, exposure to nephrotoxin
- Uremic symptoms if severe: nausea, confusion, dyspnea
Signs / physical exam
- Volume status variable — euvolemic, overloaded, or depleted depending on cause and management
- Findings of underlying critical illness
- Skin findings in atheroemboli (livedo, blue toes)
- Bladder not distended; no obstruction
Classic findings
Muddy brown granular casts in urine sediment are pathognomonic for ATN.
Differential diagnosis
- Prerenal AKI — BUN:Cr >20:1, FENa <1%, bland sediment; responsive to volume — distinguish before fluid challenge
- Acute interstitial nephritis — Drug exposure (PPI, NSAID, beta-lactam), fever, rash, eosinophilia, WBC casts
- Glomerulonephritis — Dysmorphic RBCs, RBC casts, proteinuria, hypertension — biopsy-driven diagnosis
- Postrenal obstruction — Hydronephrosis on US, distended bladder, anuria; rapid reversal with drainage
- Renal atheroembolic disease — Days-weeks after vascular procedure; livedo reticularis, blue toes, eosinophilia, eosinophiluria
- Contrast-induced nephropathy — Cr rise within 24-72 h of IV contrast; typically resolves by day 7-10
Diagnostic workup
Diagnostic criteria
Clinical diagnosis: AKI meeting KDIGO criteria with characteristic sediment (muddy brown casts), FENa >2%, recent ischemic or nephrotoxic event, and exclusion of prerenal/postrenal/other intrinsic causes. Biopsy rarely needed.
Labs
- BMP — rise in creatinine and BUN, often with hyperkalemia, acidosis
- Urinalysis with microscopy — muddy brown granular casts, renal tubular epithelial cells, FENa >2%
- Urine sodium >40 mEq/L, urine osmolality <350 (isosthenuria — inability to concentrate)
- CK if rhabdomyolysis suspected; LDH and haptoglobin if hemolysis suspected
- SPEP/UPEP with free light chains if multiple myeloma suspected
Imaging
- Renal ultrasound to exclude obstruction; kidneys typically normal-sized and echotexture
- CT only if specific cause suspected (atheroembolic disease, masses)
Diagnostic algorithm
| Phase | Duration | Features | Management Priority |
|---|---|---|---|
| Initiation | Hours-days | Reversible injury; Cr rising | Identify cause; remove nephrotoxin; optimize perfusion |
| Maintenance | 1-3 weeks | Established AKI; oliguria; peak Cr | Supportive care; RRT if AEIOU criteria; avoid further insults |
| Recovery | Days-weeks | Polyuria; tubular regeneration | Replace losses; monitor K, Mg, PO4; gradual return of function |
Treatment
First-line
- Remove or treat underlying cause: stop offending nephrotoxin, treat sepsis, restore perfusion
- Optimize hemodynamics: target MAP ≥65 with isotonic crystalloid and vasopressors (norepinephrine first-line) as needed
- Adjust renally cleared medications (vancomycin, gabapentin, opioids, DOACs)
- Avoid further insults: NSAIDs, ACEi/ARB during acute phase, iodinated contrast, aminoglycosides
- Conservative management — no specific therapy reverses established ATN; focus is supportive while tubules regenerate
Second-line / adjunct
- Loop diuretic — furosemide, bumetanide — for volume overload only; does not change ATN course or improve mortality
- Renal replacement therapy for KDIGO indications (AEIOU): refractory acidosis, hyperkalemia, ingestion of dialyzable toxin, volume overload, uremic complications
- Modality choice: CRRT preferred in hemodynamically unstable ICU patients; intermittent HD in stable patients
- Nutrition support: avoid protein restriction (associated with worse outcomes)
- During recovery (polyuric phase): replace urinary losses; monitor for hypokalemia, hypomagnesemia, hypophosphatemia
Complications
- Volume overload, pulmonary edema
- Hyperkalemia with cardiac arrhythmia
- Metabolic acidosis (high anion gap from retained acids)
- Uremic complications: pericarditis, encephalopathy, bleeding
- Failure to recover, transition to CKD/ESRD (~25% of severe ATN)
- Death — especially in septic ATN (40-60% in ICU)
PANCE pearls
- Muddy brown granular casts + renal tubular epithelial cells = ATN sediment.
- Three phases: initiation (insult), maintenance (oliguria, peak Cr, 1-3 weeks), recovery (polyuria, watch electrolytes).
- Diuretics do not change outcome but help volume management. 'Furosemide stress test' (no response to 1-1.5 mg/kg) predicts severe AKI.
- Nonoliguric ATN has better prognosis than oliguric.
- No medication has been shown to reverse or shorten ATN. Dopamine, fenoldopam, mannitol, and 'renal-dose' dopamine are not recommended.
References
- KDIGO 2012 — KDIGO Clinical Practice Guideline for Acute Kidney Injury
- ADQI — Acute Disease Quality Initiative consensus statements on AKI biomarkers and management
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