Acute Tubular Necrosis

Acute tubular necrosis (ATN) is acute kidney injury from ischaemic or toxic damage to tubular epithelial cells, and is the commonest cause of intrinsic AKI in hospitalised patients (about 45% of in-hospital AKI).

• Ischaemic ATN follows prolonged prerenal insult: sepsis, haemorrhage, cardiogenic shock, major surgery, hepatorenal states.
• Nephrotoxic ATN: aminoglycosides, vancomycin with piperacillin-tazobactam, amphotericin B, cisplatin, iodinated contrast, NSAIDs, calcineurin inhibitors, tenofovir.
• Pigment nephropathy: rhabdomyolysis (myoglobin), haemolysis (haemoglobin).
• Crystal and cast: tumour lysis, methotrexate, aciclovir, myeloma light chains.
• Pathophysiology: proximal tubule brush border loss, cell sloughing with cast obstruction, back-leak of filtrate, and persistent medullary hypoxia.
• Phases: initiation, maintenance (typically 1 to 2 weeks, oliguria or non-oliguria), then recovery with polyuria.
• Mortality 20 to 50% in ICU, and survivors have a raised risk of chronic kidney disease.

• Oliguria (under 400 mL/day) or non-oliguric rise in creatinine, volume overload, hyperkalaemia, metabolic acidosis, uraemic symptoms.
• Context of hypotension, sepsis, nephrotoxin or contrast exposure, or muscle injury.
• Postural hypotension and dryness favour prerenal disease instead; the response to fluids separates the two.
• Recovery phase brings polyuria with sodium, potassium, magnesium and phosphate wasting.

• Urine microscopy: muddy brown granular and epithelial cell casts (UMS score), versus bland sediment in prerenal azotaemia.
• Urine sodium over 40 mmol/L, FENa over 2% (FEurea over 35% if on diuretics), urine osmolality about 300 mOsm/kg, urine to plasma creatinine ratio under 20.
• Urinary NGAL and kidney injury biomarkers separate ATN from prerenal disease.
• Renal ultrasound to exclude obstruction. Creatine kinase, uric acid, free light chains, drug levels (vancomycin, aminoglycosides).
• Furosemide stress test (1 mg/kg IV; urine under 200 mL in 2 hours predicts progression).
• Biopsy only for atypical course (no recovery after 3 to 4 weeks).

• Remove the cause: stop nephrotoxins, treat sepsis, restore perfusion.
• Fluids: balanced crystalloid (Ringer lactate) to euvolaemia, then avoid overload. Target mean arterial pressure 65 mmHg or higher with norepinephrine 0.05 to 0.5 micrograms/kg/min.
• Diuretics only for overload: furosemide 40 to 120 mg IV or infusion 5 to 20 mg/h. They do not alter outcomes.
• Treat hyperkalaemia: calcium gluconate 10% 10 to 20 mL, insulin 10 units with 25 g glucose, salbutamol 10 to 20 mg nebulised, sodium zirconium cyclosilicate 10 g.
• Adjust drug doses to GFR, avoid NSAIDs, contrast and further nephrotoxins.
• Rhabdomyolysis: crystalloid to urine output 200 to 300 mL/h.
• Renal replacement therapy for refractory hyperkalaemia, acidosis (pH under 7.1), pulmonary oedema, uraemic pericarditis or encephalopathy. Early initiation without these indications gives no benefit. Use continuous therapy for haemodynamic instability.
• Nutrition 20 to 30 kcal/kg/day with protein 1.0 to 1.5 g/kg/day.
• Follow up creatinine, blood pressure and proteinuria at 3 months to detect CKD.