Definition - 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.
Epidemiology - 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
Aetiology - 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
Pathophysiology - 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
Investigations- 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
- Fractional excretion of chloride
- Urinalysis for sediment
- tubular epithelial cells, epithelial cell casts, or muddy brown casts supports ATN
- FBC
- platelet aggregation studies
- urinary myoglobin
Managementa) 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- 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
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