What are the signs and symptoms of Acute Tubular Necrosis (ATN)?

Signs and Symptoms of Acute Tubular Necrosis (ATN)

ATN typically presents with decreased urine output (oliguria), elevated serum creatinine, and characteristic urinary findings including tubular epithelial cells and granular casts, often occurring in the context of recent nephrotoxic exposure, hypotension, sepsis, or major surgery. 1

Clinical Presentation

Urinary Changes

• Oliguria (urine output <400 mL/day) is the most common presenting sign and is universally associated with increased mortality across all ATN subtypes 2
• Decreased urine output may be the first detectable sign in at-risk patients 3
• However, ATN can present with non-oliguric renal failure where urine output remains normal or even elevated 4

Laboratory Findings

Serum Markers:

• Progressive increase in serum creatinine, typically ≥0.3 mg/dL within 48 hours or ≥50% increase within 7 days 5
• Elevated blood urea nitrogen (BUN) 6
• Hyperkalemia, metabolic acidosis, and electrolyte disturbances develop as kidney function deteriorates 7

Urinary Markers:

• Fractional excretion of sodium (FENa) >1% distinguishes ATN from prerenal causes (FENa <1%) 1
• Urinary sodium concentration >20 mEq/L (compared to <10 mEq/L in prerenal AKI) 1
• Fractional excretion of urea (FEUrea) >50% suggests ATN, while <35% suggests prerenal causes 1
• Proteinuria typically <500 mg/day without significant albuminuria, helping exclude glomerular diseases 1

Urinalysis Findings:

• Tubular epithelial cells in urine sediment 1
• Granular casts (muddy brown casts) 1
• Renal tubular epithelial cell casts 1
• Absence of significant hematuria (<50 RBCs per high-power field) helps distinguish from glomerulonephritis 1
• Absence of microhematuria differentiates ATN from acute glomerulonephritis 1

Clinical Context and Risk Factors

Common Precipitating Events:

• Recent exposure to nephrotoxic medications (NSAIDs, aminoglycosides, contrast agents) 1, 7
• Hypotension or hemodynamic instability 1
• Sepsis 1
• Major surgery, particularly cardiac or vascular procedures 1
• Recent hypovolemia during concurrent illness (respiratory, urinary, or gastrointestinal infections) 5

Associated Complications

Systemic Manifestations:

• Multiple organ failure occurs more frequently in ischemic and mixed ATN (46-55%) compared to nephrotoxic ATN (7%) 2
• Gastrointestinal bleeding is more prevalent in ischemic and mixed ATN 2
• Hypervolemia and fluid overload unresponsive to diuretics 7, 2
• Uremic symptoms including encephalopathy and pericarditis in severe cases 7

Physical Examination Findings

• Volume status assessment is critical—look for signs of hypovolemia (orthostatic hypotension, decreased skin turgor) or hypervolemia (edema, pulmonary congestion) 5
• Blood pressure abnormalities including hypotension or hypertension 5
• Edema may be present as a nonkidney manifestation 5

Diagnostic Pitfalls

Key Differentiating Features:

• Unlike hepatorenal syndrome, ATN shows FENa >1%, urinary sodium >20 mEq/L, and abnormal urinary sediment with tubular cells and casts 5, 1
• Unlike prerenal azotemia, ATN does not respond to volume expansion and maintains elevated FENa 1
• Unlike glomerulonephritis, ATN shows absence of dysmorphic RBCs, RBC casts, and significant proteinuria 1

Emerging Biomarkers

• Urinary NGAL (neutrophil gelatinase-associated lipocalin) with cutoff values of 220-244 μg/g creatinine can differentiate ATN from prerenal azotemia or hepatorenal syndrome 5
• Kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) may provide earlier and more specific diagnosis of tubular injury 1
• These biomarkers are particularly useful when measured 2 days following fluid challenge 5

Clinical Course

ATN progresses through distinct phases 6:

• Renal failure phase: Oliguria, rising creatinine, electrolyte abnormalities
• Diuretic phase: Polyuria as tubular function begins recovering
• Recovery phase: Gradual normalization of kidney function over weeks to months

Critical caveat: Even with functional recovery, cellular repair is often abnormal ("maladaptive repair"), leading to accelerated renal aging and increased susceptibility to chronic kidney disease 4