Biomarkers of Kidney Function: BUN to Creatinine Ratio

Optimal Takeaways

BUN and creatinine are produced from dietary protein, tissue breakdown (BUN), and muscle metabolism (creatinine). Both must be excreted by the kidney. A decreasing ratio is associated with renal failure, protein deficiency, severe muscle breakdown, and reduced BUN production due to liver failure. An increasing ratio suggests acute temporary kidney injury, excess protein intake, tissue breakdown, GI bleeding, and dehydration. An elevated ratio is also associated with increased risk of mortality from myocardial infarction and COVID-19.

Standard Range: 6.00 – 22.00 Ratio (0.02 – 0.09 Ratio)  

The ODX Range: 10.00 – 16.00 Ratio (0.04 – 0.06 Ratio)

Low BUN:Creatinine ratio may indicate kidney injury, decreased function, and renal failure especially if below 10 (Raymond 2021). A low ratio is also associated with inadequate protein intake, excess excretion of urea (e.g., sickle cell anemia), increased creatinine production (e.g., rhabdomyolysis), and decreased urea synthesis (e.g., advanced liver disease (Hosten 1990).

A low ratio may be associated with acute interstitial nephritis (Salvador 2023). oxidative stress, inflammation, and endothelial dysfunction (Shen 2022).

High BUN:Creatinine ratio may indicate transient kidney dysfunction, especially above 20 (Raymond 2021). Temporary non-renal causes of an increased ratio include excess protein intake, GI bleeding, catabolic states such as fever or burns), dehydration, shock, congestive heart failure, or urinary tract obstruction (Hosten 1990).

An elevated ratio is also associated with increased risk of coronary artery disease in type 2 diabetics (Liu 2022), mortality from myocardial infarction and acute heart failure (Qian 2019), poorer outcomes in those with congestive heart failure (Tolomeo 2023).and increased severity and mortality from COVID-19 (Ok 2021).

A BUN:Creatinine ratio above 15 was also associated with acute ischemic stroke due to venous thromboembolism caused by dehydration (Kim 2017), as well as poor outcomes in acute ischemic stroke (Schrock 2012).­

Overview

As end products of nitrogen metabolism, BUN and creatinine reflect protein, muscle, and renal status. The ratio of BUN to creatinine provides information about what type of dysfunction may be present. If the ratio increases above 20, dysfunction is likely a “pre-renal” cause outside the kidney and may resolve. However, if the ratio decreases below 10, then intrinsic acute kidney damage may be present, possibly from severe infection, ischemia, trauma, surgical accident, or cardiogenic shock, and will remain low with renal failure (Raymond 2021). A BUN:Creatinine ratio of 15.5 is considered normal (Pagana 2021).

A large study evaluated the BUN:Creatinine ratio in 42,038 subjects from the general population. A U-shaped association was observed between the ratio and all-cause mortality which was greatest with a ratio below 11.43 or a ratio of 18.57 or above. The lowest all-cause mortality was observed with a ratio of 11.43 – 14.64. Those with a higher ratio tended to be older, female, drink more, and have hypertension, CVD, and diabetes. However, interestingly, cancer-related mortality was lowest in those with a higher ratio of 18.57 or above (Shen 2022).

An increased ratio is also indicative of disease severity in COVID-19. The coronavirus that causes COVID-19 enters kidney cells in an ACE2-dependent manner causing renal vasoconstriction and activation of RAAS that reduces BUN excretion while allowing creatinine excretion. Investigation of 139 COVID-19 patients suggests that the BUN:Creatinine ratio may be an independent predictor of severity and survival. A value above 33.5 was associated with increased risk of severe disease while a ratio above 51.7 was associated with mortality (Ok 2021).

Assessing BUN:Creatinine ratio may help identify the source of gastrointestinal bleeding. Retrospective review of 621 acute GI bleed cases found that a cut-off of 35 or above was highly likely to be associated with an upper versus a lower bleed (Zia 2019).

References

Hosten, Adrian O. “BUN and Creatinine.” Clinical Methods: The History, Physical, and Laboratory Examinations, edited by H Kenneth Walker et. al., 3rd ed., Butterworths, 1990.

Kim, Hoon et al. “Elevated Blood Urea Nitrogen/Creatinine Ratio Is Associated with Venous Thromboembolism in Patients with Acute Ischemic Stroke.” Journal of Korean Neurosurgical Society vol. 60,6 (2017): 620-626. doi:10.3340/jkns.2016.1010.009

Liu, Feng et al. “Elevated blood urea nitrogen-to-creatinine ratio increased the risk of Coronary Artery Disease in patients living with type 2 diabetes mellitus.” BMC endocrine disorders vol. 22,1 50. 28 Feb. 2022, doi:10.1186/s12902-022-00954-3

Ok, Fesih et al. “Predictive values of blood urea nitrogen/creatinine ratio and other routine blood parameters on disease severity and survival of COVID-19 patients.” Journal of medical virology vol. 93,2 (2021): 786-793. doi:10.1002/jmv.26300  

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Qian, Hao et al. “Predictive value of blood urea nitrogen/creatinine ratio in the long-term prognosis of patients with acute myocardial infarction complicated with acute heart failure.” Medicine vol. 98,11 (2019): e14845. doi:10.1097/MD.0000000000014845

Raymond, Janice L., et al. Krause and Mahan's Food & the Nutrition Care Process. Elsevier, 2021.

Salvador, López Giacoman et al. “A low BUN/creatinine ratio predicts histologically confirmed acute interstitial nephritis.” BMC nephrology vol. 24,1 75. 27 Mar. 2023, doi:10.1186/s12882-023-03118-0

Shen, Song et al. “The blood urea nitrogen/creatinine (BUN/cre) ratio was U-shaped associated with all-cause mortality in general population.” Renal failure vol. 44,1 (2022): 184-190. doi:10.1080/0886022X.2022.2030359

Schrock, Jon W et al. “Elevated blood urea nitrogen/creatinine ratio is associated with poor outcome in patients with ischemic stroke.” Clinical neurology and neurosurgery vol. 114,7 (2012): 881-4. doi:10.1016/j.clineuro.2012.01.031

Tolomeo, Paolo et al. “Independent prognostic importance of blood urea nitrogen to creatinine ratio in heart failure.” European journal of heart failure, 10.1002/ejhf.3114. 20 Dec. 2023, doi:10.1002/ejhf.3114

Zia Ziabari, Seyyed Mahdi et al. “Blood Urea Nitrogen to Creatinine ratio in Differentiation of Upper and Lower Gastrointestinal Bleedings; a Diagnostic Accuracy Study.” Archives of academic emergency medicine vol. 7,1 e30. 2 Jun. 2019