Research Blog

December 9, 2022

Renal Biomarkers: BUN 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.

Conventional Lab Range: 6.00 – 22.00 Ratio (0.02 – 0.09 Ratio)  

Optimal Dx’s Optimal 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 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 mortality from myocardial infarction and acute heart failure (Qian 2019), as well as increased severity and mortality from COVID-19 (Ok 2021).

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).

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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.

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.

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

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

 

Tag(s): Biomarkers

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