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
underlying renal disease
low renal perfusion
excessive fluid loss
exposure to nephrotoxins
exposure to radio-contrast media
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.
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
Direct tubular toxicity
Nephrotoxic potential of most agents is dramatically increased in the presence of borderline or overt ischaemia, sepsis, or other renal insults
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)
oliguria or anuria
poor oral intake and anorexia
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
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
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))
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
anaemia, prolonged PTT
platelet aggregation studies
Nephrotoxins should be ceased (preferable) or if this is not possible, dose should be decreased.
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)
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