From the Guidelines
Elevated blood urea nitrogen (BUN) levels can result from several causes, primarily related to kidney dysfunction, dehydration, or increased protein metabolism, and it is essential to consider the BUN-to-creatinine ratio and assess for symptoms like fatigue, decreased urination, swelling, or confusion that might indicate underlying kidney problems. Kidney disease or failure is a common cause, as damaged kidneys cannot effectively filter urea from the blood 1. Dehydration concentrates blood components, including BUN, leading to higher readings. Excessive protein intake or increased protein catabolism, such as during gastrointestinal bleeding, muscle breakdown, or high-dose corticosteroid treatment, can also raise BUN levels. Certain medications like NSAIDs, antibiotics (gentamicin, vancomycin), and diuretics can impair kidney function or alter fluid balance, causing BUN elevation 1. Heart failure may reduce blood flow to the kidneys, impairing their filtering ability. Other causes include urinary tract obstruction, which prevents urea excretion, and severe burns or infections that increase protein breakdown.
Some key points to consider when evaluating elevated BUN include:
- Kidney function: Assess for signs of kidney disease or failure, such as decreased urination, swelling, or confusion 1
- Dehydration: Evaluate for signs of dehydration, such as dry mouth, dark urine, or decreased blood pressure 1
- Medications: Review medications that may impair kidney function or alter fluid balance, such as NSAIDs, antibiotics, or diuretics 1
- Protein intake: Assess for excessive protein intake or increased protein catabolism, such as during gastrointestinal bleeding or muscle breakdown 1
- Heart failure: Evaluate for signs of heart failure, such as shortness of breath, fatigue, or swelling 1
When managing elevated BUN, it is crucial to:
- Monitor blood chemistry frequently and serially until potassium and creatinine have plateaued 1
- Adjust concomitant medications, such as stopping nephrotoxic drugs or reducing diuretic dose 1
- Consider specialist advice if potassium or creatinine levels exceed acceptable limits 1
From the FDA Drug Label
Reversible elevations of BUN may occur and are associated with dehydration, which should be avoided, particularly in patients with renal insufficiency Minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 2% of patients with hypertension treated with lisinopril alone.
The reasons for elevated BUN include:
- Dehydration, which should be avoided, particularly in patients with renal insufficiency 2
- Renal insufficiency 2
- Concomitant diuretic therapy 3
- Renal artery stenosis 3
- Acute myocardial infarction 3
- Lisinopril therapy 3
From the Research
Elevated BUN: Reasons and Associations
- Elevated blood urea nitrogen (BUN) is associated with worse outcomes in heart failure patients, including higher all-cause mortality 4, 5, 6, 7
- A high BUN/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF) and is independently associated with higher post-discharge all-cause mortality 4
- The predictive value of a high BUN/creatinine ratio at discharge is haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution 4
- High BUN is an independent predictor of all-cause mortality in heart failure, and lower BUN is associated with better prognosis in patients with heart failure 5
- The BUN/creatinine ratio is associated with worse outcomes in chronic heart failure, independently of estimated glomerular filtration rate (eGFR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 6
- Elevated BUN is also associated with higher risk of all-cause death in patients hospitalized for acute decompensated heart failure, particularly when combined with low serum sodium 7
Heart Failure and BUN
- Heart failure patients with elevated BUN have a higher risk of all-cause mortality, regardless of whether they have reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) 5, 6
- The association between BUN and outcomes in heart failure is significant, even after adjustment for other prognostic variables, including eGFR and NT-proBNP 6
- Elevated BUN may reflect neurohumoral activation, altered renal blood flow, or other pathophysiologic mechanisms not incorporated in conventional prognostic variables 6
Clinical Implications
- Elevated BUN should be considered a prognostic indicator in heart failure patients, and its measurement may help identify patients at higher risk of adverse outcomes 4, 5, 6, 7
- The BUN/creatinine ratio may be a useful tool for risk stratification in heart failure patients, particularly in those with acute decompensated heart failure 4
- Further research is needed to fully understand the mechanisms underlying the association between elevated BUN and worse outcomes in heart failure, and to determine the optimal strategies for managing elevated BUN in these patients 4, 5, 6, 7