What are the causes of elevated Blood Urea Nitrogen (BUN) and Creatinine levels, indicating Impaired Renal Function?

Causes of Elevated BUN and Creatinine Levels

Elevated Blood Urea Nitrogen (BUN) and creatinine levels primarily indicate impaired renal function, which can result from pre-renal, intrinsic renal, or post-renal causes. The pattern of elevation and the BUN/creatinine ratio provide important diagnostic clues to the underlying etiology.

Pre-renal Causes (BUN/Creatinine Ratio >20:1)

• Decreased renal perfusion due to:

  • Dehydration or volume depletion 1, 2
  • Heart failure with reduced cardiac output 2, 3
  • Hypotension or shock (septic or hypovolemic) 4
  • Renal artery stenosis 5

• Increased protein catabolism from:

  • High protein intake or parenteral nutrition 4
  • Gastrointestinal bleeding (blood in gut acts as protein load) 4
  • Corticosteroid use 4
  • Hyperthyroidism (causing excessive protein breakdown) 6

Intrinsic Renal Causes (BUN/Creatinine Ratio 10-15:1)

• Acute kidney injury from:

  • Nephrotoxic medications (NSAIDs, ACE inhibitors, ARBs) 5
  • Contrast-induced nephropathy 7
  • Acute tubular necrosis 7

• Chronic kidney disease due to:

  • Hypertension-induced nephrosclerosis 7
  • Diabetic nephropathy 7
  • Glomerulonephritis 7
  • Multiple myeloma (causing cast nephropathy) 7

Post-renal Causes (Variable BUN/Creatinine Ratio)

• Urinary tract obstruction from:
  • Prostatic hyperplasia 8
  • Nephrolithiasis (kidney stones) 8
  • Malignancy (bladder, prostate, or cervical cancer) 8

Medication-Related Causes

• ACE inhibitors like lisinopril can cause:

  • Reversible increases in BUN and creatinine (up to 20%) 5
  • More significant elevations in patients with renal artery stenosis 5
  • Higher incidence of renal dysfunction in heart failure patients on concomitant diuretics 5

• Diuretics can cause:

  • Pre-renal azotemia due to volume depletion 5
  • Elevated BUN/creatinine ratio >20:1 2

Clinical Pearls and Pitfalls

• BUN levels are more influenced by extra-renal factors than creatinine, making the BUN/creatinine ratio a valuable diagnostic tool 8

• A disproportionately elevated BUN (BUN/creatinine ratio >20:1) most commonly indicates pre-renal azotemia rather than intrinsic kidney disease 4, 2

• In elderly patients, severely disproportionate BUN/creatinine ratios are more common due to lower muscle mass, and often indicate multiple contributing factors 4

• Baseline BUN is the renal parameter most strongly associated with mortality in hospitalized heart failure patients, more so than creatinine or eGFR 9, 3

• Always evaluate hydration status when encountering elevated BUN and creatinine, as simple rehydration may correct pre-renal causes 2

• Consider temporarily discontinuing medications that may worsen kidney function (NSAIDs, ACE inhibitors, ARBs) when elevated BUN and creatinine are detected 2, 5

• Multiple myeloma should be considered in patients with unexplained renal dysfunction, especially when accompanied by hypercalcemia, anemia, or bone pain 7