Acute tubular necrosis

  • Reversible or irreversible type of renal failure caused by ischaemic or toxic injury to the renal tubular epithelial cells
  • Results in cell death or detachment from basement membrane causing tubular dysfunction
Risk Factors
  • underlying renal disease
  • low renal perfusion
  • diabetes mellitus
  • hypotension
  • excessive fluid loss
  • major surgery
  • mechanical ventilation
  • exposure to nephrotoxins
  • exposure to radio-contrast media
  • muscle trauma
  • haemolysis
  • hyper-uricaemia
  • infection
  • advanced age
  • multiple myeloma
  • sepsis
  • pancreatitis
Differential diagnosis
  • Pre-renal azotaemia 
    • Oliguria is much more frequent.
    • Urea to creatinine ratio is >20:1. 
    • Urinalysis: osmolality is normal, sodium levels, ratio of urine to plasma creatinine. 
    • Ratio of urine to plasma creatinine levels are high and the urinary sodium concentration is low.
  • Intrinsic renal azotaemia  
    • Patients with glomerular disease typically present with proteinuria and microscopic haematuria.
    • Urinalysis shows proteinuria and microscopic haematuria.
  • Estimated to account for 76% cases of ARF in critical care units
  • 19.2 cases of ARF per 1000 hospitalisations in the US
  • UK incidence of ARF ranges from 172 per million population (pmp) per year to up to 630 pmp per year, depending on the study
  • Ischaemic
    • Systemic hypo-perfusion
    • Local hypo-perfusion
  • Exogenous toxins
    • Intra-renal vasoconstriction
    • Direct tubular toxicity
    • Tubular obstruction
    • Nephrotoxic potential of most agents is dramatically increased in the presence of borderline or overt ischaemia, sepsis, or other renal insults
  • Endogenous toxins
    • Increased haeme (from myoglobin release as in rhabdomyolysis, or increased haemoglobin release as in haemolysis)
    • Increased uric acid (e.g., gout)
    • Increased light chain proteins (e.g., myeloma of kidney)
Clinical features
  • Common:
    • oliguria or anuria
    • hypotension
    • tachycardia
  • Less common:
    • poor oral intake and anorexia
    • malaise
    • thirst
    • dizziness
    • orthopnoea/dyspnoea
    • oedema
  • Initiation phase
    • Injury is evolving but not yet established
    • As the dysfunction progresses, cell death and detachment from the basement membrane cause tubular necrosis
      • Reduces blood volume and renal perfusion
    • Acute decrease in GFR to low levels, with a sudden increase in serum creatinine and blood urea nitrogen concentrations
    • ATN is potentially preventable during this period
  • Maintenance phase
    • Renal injury is established
    • Endothelial cell necrosis and sloughing lead to tubular obstruction and increased tubular permeability
    • Sustained severe reduction in GFR at 5 to 10 mL/minute
    • Creatinine and urea continue to rise and oliguria (diminished urine volume) may be present
    • Results in azotaemia, fluid retention, electrolyte imbalance, and metabolic acidosis
    • This phase may last from several days to months
    • Oliguria and a prolonged maintenance phase are signs of poor renal prognosis
  • Recovery phase
    • Patients recover renal function through repair and regeneration of renal tissue
    • Growth factors are released that aid in repair by promoting the proliferation of renal tubular cells
    • Tubular function is restored, and is characterised by
      • increase in urine volume (if oliguria was present during the maintenance phase)
      • gradual decrease in urea and serum creatinine to their pre-insult levels
  • Basic metabolic profile (including urea and creatinine)
    • elevated serum creatinine, elevated urea, hyperkalaemia, or metabolic acidosis suggests acute tubular necrosis (ATN) 
  • Urea to creatinine ratio
    • 10:1 or higher supports ATN 
  • Urine sodium concentration 
    • elevated (>40 mmol/L (40 mEq/L)) 
  • Urine osmolality
    • less than 450 mOsmol/kg supports ATN 
  • Fractional excretion of sodium 
    • over 2% supports ATN 
  • Fractional excretion of chloride 
    • over 2% supports ATN 
  • Urinalysis for sediment
    • tubular epithelial cells, epithelial cell casts, or muddy brown casts supports ATN 
  • FBC 
    • anaemia, prolonged PTT 
  • platelet aggregation studies 
    • prolonged
  • urinary myoglobin 
    • elevated

a) conservative
  • Nephrotoxins should be ceased (preferable) or if this is not possible, dose should be decreased.
b) medical
  • There is no specific therapy for ATN apart from supportive care in maintaining volume status and controlling electrolyte and acid-base abnormalities
  • The underlying cause of volume contraction or blood loss needs to be treated along with restoring euvolaemia and haemodynamic stability. 
  • Crystalloid (normal saline or lactated Ringers) is sufficient in most cases for volume expansion. 
  • Volume expansion with normal saline has been demonstrated to be beneficial in the reducing risk of contrast-induced nephropathy.
    • Target doses of normal saline at 1 mL/kg/hour have been demonstrated to have benefit
  • Haemorrhage requires blood product replacement. 
  • For oliguric ATN, furosemide (a loop diuretic) if administered early in course of ischaemic injury can maintain urine output
  • In case of severe acidosis or volume overload refractory to diuretics or hyperkalaemia or uraemia:
    • Conventional haemodialysis in haemodynamically stable patients.
    • Other modes of renal replacement
      • Continuous renal replacement therapies (CRRT
        • Continuous venovenous haemofiltration (CVVH)
        • Continuous venovenous haemodialysis (CVVHD)
        • Continuous venovenous haemodiafiltration (CVVHDF)
c) surgical

  • Prognosis is good in otherwise healthy patients when the underlying insult is corrected
  • If there was pre-existing renal disease, or if acute tubular necrosis (ATN) has presented with prolonged anuria, the prognosis is poor
    • Patient may eventually require renal-replacement therapy (RRT)
  • Prognosis is better in a non-ICU (37% mortality) compared with an ICU (79% mortality) setting
  • Predictors of mortality:
    • male sex, advanced age, comorbid illness, malignancy, oliguria, sepsis, mechanical ventilation, multi-organ failure, high severity of illness