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