What causes elevated blood urea nitrogen (BUN) and creatinine levels?

Causes of Elevated Blood Urea Nitrogen (BUN) and Creatinine

Elevated BUN and creatinine levels are primarily caused by impaired kidney function, but can also result from pre-renal, intrinsic renal, and post-renal conditions, with dehydration and heart failure being common reversible causes.

Pre-Renal Causes (Decreased Kidney Perfusion)

• Dehydration/Volume Depletion

  • Inadequate fluid intake
  • Excessive fluid loss (vomiting, diarrhea, excessive sweating)
  • Diuretic overuse
  • Burns
  • Hemorrhage

• Decreased Cardiac Output

  • Heart failure (BUN rises disproportionately to creatinine) 1
  • Cardiogenic shock
  • Myocardial infarction

• Vascular Causes

  • Renal artery stenosis 1
  • Hypotension
  • Septic shock 2

Intrinsic Renal Causes (Direct Kidney Damage)

• Acute Kidney Injury

  • Nephrotoxic medications (ACE inhibitors, NSAIDs, aminoglycosides, contrast media) 3
  • Rhabdomyolysis
  • Glomerulonephritis
  • Acute tubular necrosis

• Chronic Kidney Disease

  • Diabetic nephropathy 1
  • Hypertensive nephrosclerosis
  • Polycystic kidney disease
  • Chronic glomerulonephritis

Post-Renal Causes (Urinary Tract Obstruction)

• Upper Urinary Tract Obstruction

  • Kidney stones
  • Tumors
  • Retroperitoneal fibrosis

• Lower Urinary Tract Obstruction

  • Prostatic hyperplasia
  • Urethral stricture
  • Neurogenic bladder

Other Contributing Factors

• High Protein Diet/Increased Protein Catabolism 2

  • Gastrointestinal bleeding
  • High-protein nutritional supplements
  • Creatine supplements (can falsely elevate creatinine) 4
  • Tissue breakdown (burns, trauma, sepsis)

• Medications

  • ACE inhibitors/ARBs (can cause functional changes in GFR) 5, 3
  • Certain antibiotics
  • Diuretics (especially with volume depletion) 5

Clinical Patterns and Diagnostic Clues

BUN:Creatinine Ratio

• Normal ratio: 10-15:1 2, 6
• Elevated ratio (>20:1) suggests:
  • Pre-renal azotemia (dehydration, heart failure) 2
  • Gastrointestinal bleeding
  • High protein intake
  • Catabolic states (sepsis, burns)
• Normal or low ratio (<10:1) suggests:
  • Intrinsic renal disease
  • Low protein intake
  • Liver disease (decreased urea production)
  • Rhabdomyolysis (disproportionate creatinine elevation)

Assessment of Reversibility

When evaluating elevated BUN and creatinine, assess for potentially reversible causes 1:

• Evaluate volume status and cardiac function
• Review medication history (especially ACE inhibitors, ARBs, diuretics)
• Assess for urinary tract obstruction
• Check for signs of infection or sepsis

Management Considerations

1. For pre-renal causes:

   • Optimize volume status
   • Improve cardiac output in heart failure
   • Consider temporarily reducing or holding ACE inhibitors/ARBs if significant elevation (>30% from baseline) 5

2. For medication-induced elevations:

   • Continue monitoring if increases are <30% of baseline 5
   • Consider dose reduction or temporary suspension if increases are >30% 5

3. For intrinsic renal disease:

   • Refer to nephrologist if eGFR <30 mL/min/1.73m² 1, 5
   • Monitor for electrolyte abnormalities, especially hyperkalemia 3

4. For post-renal causes:

   • Address the obstruction (catheterization, surgical intervention)

Important Clinical Pitfalls

• False elevations in creatinine can occur with certain medications or supplements (e.g., creatine) 4
• Disproportionate BUN elevation is common in elderly ICU patients and often multifactorial 2
• Small increases in BUN and creatinine with ACE inhibitors/ARBs are often functional and may not indicate kidney damage 1, 3
• Elevated BUN/creatinine ratio in stroke patients is associated with poor outcomes 7
• Dehydration can worsen outcomes in various conditions and should be addressed promptly 7

Remember that trends in BUN and creatinine are often more informative than single measurements, and interpretation should always consider the clinical context.