What is ATN (Acute Tubular Necrosis)?

Acute Tubular Necrosis (ATN)

Acute Tubular Necrosis (ATN) is a form of intrinsic acute kidney injury characterized by damage to the tubular epithelial cells of the kidneys, resulting in impaired renal function and typically presenting with elevated serum creatinine, oliguria, and abnormal urinary biomarkers. 1

Definition and Pathophysiology

ATN represents a significant cause of acute kidney injury (AKI) in hospitalized patients, particularly in critical care settings. It is characterized by:

• Damage to the renal tubular epithelial cells due to ischemic or nephrotoxic insults
• Impaired renal function with reduced glomerular filtration rate
• Tubular dysfunction leading to altered handling of sodium, water, and other solutes

The pathophysiology involves:

• Tubular cell injury and death
• Tubular obstruction from cellular debris
• Back-leak of filtrate through damaged tubular epithelium
• Intrarenal vasoconstriction

Etiology

ATN can be classified into three main types based on cause:

1. Ischemic ATN (51% of cases):

   • Caused by reduced renal perfusion
   • Common in shock, severe hypotension, major surgery, trauma
   • Often associated with multiple organ failure (46% of cases) 2

2. Nephrotoxic ATN (11% of cases):

   • Caused by direct toxic injury to tubular cells
   • Common agents: antibiotics (aminoglycosides), contrast media, chemotherapeutic agents
   • Lower mortality rate (38%) compared to other forms 2

3. Mixed ATN (38% of cases):

   • Combined ischemic and nephrotoxic mechanisms
   • High rate of multiple organ failure (55%) 2

Clinical Presentation

ATN typically presents with:

• Elevated serum creatinine (increase ≥0.3 mg/dL within 48 hours or ≥50% within 7 days)
• Reduced urine output (oliguria <400 mL/day) in many but not all cases
• Urinary sediment showing renal tubular epithelial cells, granular casts, and muddy brown casts
• Signs of fluid overload in oliguric patients

Diagnosis

Diagnosis of ATN involves:

1. Clinical Assessment:

   • History of exposure to nephrotoxins or ischemic events
   • Evaluation of volume status
   • Assessment for signs of sepsis or multiorgan failure

2. Laboratory Tests:

   • Elevated serum creatinine and blood urea nitrogen
   • Urinalysis showing muddy brown casts, renal tubular epithelial cells
   • Fractional excretion of sodium (FENa) typically >1% (though may be lower with concurrent volume depletion)
   • Fractional excretion of urea (FEUrea) >28% suggests ATN rather than hepatorenal syndrome 1

3. Biomarkers:

   • Urinary neutrophil gelatinase-associated lipocalin (NGAL) >220-244 μg/g creatinine differentiates ATN from hepatorenal syndrome 1
   • Other biomarkers: kidney injury molecule-1 (KIM-1), interleukin-18, N-acetyl-β-D-glucosaminidase

4. Imaging:

   • Renal ultrasound to exclude obstruction and assess kidney size/echogenicity
   • Normal-sized or slightly enlarged kidneys in acute setting

Differential Diagnosis

Important conditions to differentiate from ATN include:

1. Pre-renal AKI:

   • Due to decreased renal perfusion
   • Rapidly reversible with volume repletion
   • FENa typically <1%, FEUrea <35%
   • Lower urinary NGAL levels

2. Hepatorenal Syndrome (HRS-AKI):

   • Functional renal failure in cirrhosis
   • Requires exclusion of other causes including ATN
   • Lower urinary NGAL (<220 μg/g creatinine) 1
   • FEUrea <28% 1

3. Post-renal AKI:

   • Due to urinary tract obstruction
   • Identified by imaging studies showing hydronephrosis

Management

Management of ATN focuses on supportive care and prevention of complications:

1. Eliminate Nephrotoxic Agents:

   • Discontinue all potentially nephrotoxic medications
   • Avoid contrast media when possible

2. Optimize Hemodynamics and Volume Status:

   • Ensure adequate renal perfusion
   • Cautious fluid management to avoid volume overload
   • In patients with cirrhosis, albumin administration (1 g/kg up to 100 g/day) may be beneficial 1

3. Manage Electrolyte and Acid-Base Disturbances:

   • Monitor and correct hyperkalemia, metabolic acidosis
   • Restrict potassium and phosphate intake as needed

4. Nutritional Support:

   • Provide adequate nutrition while avoiding excessive protein load
   • Enteral nutrition preferred over parenteral when possible 3

5. Prevent and Treat Complications:

   • Vigilant monitoring for infection, especially in critically ill patients
   • Avoid unnecessary catheters and invasive procedures 3

6. Renal Replacement Therapy (RRT):

   • Indications: severe hyperkalemia, acidosis, volume overload, uremic symptoms
   • Continuous RRT preferred in hemodynamically unstable patients 1
   • More intensive dialysis may improve outcomes in selected patients 3

Prognosis

The prognosis of ATN varies based on:

• Underlying cause (nephrotoxic ATN has better outcomes than ischemic or mixed)
• Presence of oliguria (independent risk factor for mortality) 2
• Comorbidities and presence of multiorgan failure
• Age and baseline renal function

Mortality rates:

• Overall hospital mortality: 37-62% 4, 2
• ICU patients: 63-79% 4, 2
• Nephrotoxic ATN: 38% mortality (significantly lower than other types) 2

Prevention

Preventive strategies include:

• Maintaining adequate renal perfusion during high-risk procedures
• Proper hydration before contrast administration
• Dose adjustment of nephrotoxic medications
• Monitoring drug levels for potentially nephrotoxic agents
• Early recognition and treatment of sepsis and shock

In patients with cirrhosis, specific preventive measures include avoiding nephrotoxic drugs, monitoring serum creatinine during diuretic therapy, and albumin infusion with therapeutic paracentesis 1.