Blood Urea Nitrogen (BUN) is a waste product produced by protein metabolism that is filtered out of the blood by the kidneys. High levels of BUN may indicate kidney disease or damage.
Arginine is another key amino acid in the urea cycle. Disruption of arginine metabolism in the urea cycle, such as in arginase deficiency, can result in high BUN levels.
M. A. M. M. Mori, S. L. Lin, H. S. Lam, C. M. Schooling. L-arginine supplementation accelerates renal fibrosis and increases mortality in MRL/lpr mice. Kidney International (2003). https://pubmed.ncbi.nlm.nih.gov/12631354/
Citrulline is an amino acid produced in the urea cycle that removes excess nitrogen. Impairment of the urea cycle can lead to elevated BUN levels. Citrulline levels may reflect urea cycle function and its effect on BUN.
J.M. Breuillard, L. Cynober, C. Moinard, P. Crenn, E. Curis, J.C. Chaumeil, L. Cynober, S. Sfar. Manipulation of citrulline availability in humans. American Journal of Physiology - Gastrointestinal and Liver Physiology (2007). https://journals.physiology.org/doi/10.1152/ajpgi.00289.2007
A. Hashemi, M.H. Hashemi, M. Khoshbaten, M. Sadeghi, S.M. Ghaedi. The Effect of L-Citrulline Supplementation on Outcomes of Cardiovascular Diseases: A Systematic Review and Meta-Analysis. Nutrients (2023). https://www.mdpi.com/2072-6643/15/5/1234
E. Aguayo, A. Martínez-Sánchez, B. Fernández-Lobato, F. Alacid. L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health. Applied Sciences (2021). https://doi.org/10.3390/app11073293
Creatinine and BUN are both waste products filtered out of the blood by the kidneys. As kidney function declines, creatinine and BUN levels rise in tandem, making them key markers of kidney health and function.
Sujino, Y., Nakano, S., Tanno, J., Shiraishi, Y., Goda, A., Mizuno, A., Nagatomo, Y., Kohno, T., Muramatsu, T., Nishimura, S., Kohsaka, S., and Yoshikawa, T.. Clinical implications of the blood urea nitrogen/creatinine ratio in heart failure and their association with haemoconcentration. ESC Heart Failure (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989280/
Elevated homocysteine is associated with chronic kidney disease. Kidney dysfunction can impair homocysteine clearance while also raising BUN levels. The two markers may be correlated in kidney disease.
Qianhong Yang, Youwei Lu, Yanhua Deng, Jiayi Xu, Xi Zhang. Homocysteine level is positively and independently associated with serum creatinine and blood urea nitrogen (BUN) levels in old male patients with hypertension. NCBI (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581807/
Yongchao Zhang, Xiaoli Zhang, Jing Wang, Xiangyu Zhang, Yingying Zhang, Jian Wang. Relationship between plasma homocysteine and chronic kidney disease in US patients with type 2 diabetes mellitus: a cross-sectional study. BMC Nephrology (2022). https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-022-03045-6
Hui-Yun Lin, Chih-Ying Chang, Hui-Wen Chang, Chun-Chieh Yeh, Chien-Hsiung Weng. Association between Homocysteine and Vitamin D Levels in Chronic Kidney Disease. MDPI (2023). https://www.mdpi.com/2072-6643/16/8/1155
Hsin-Yi Chang, Chien-Hsiung Weng. Association between plasma total homocysteine level within normal range and chronic kidney disease in the elderly. NCBI (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559759/
Ornithine is an amino acid produced from arginine in the urea cycle. Like citrulline and arginine, changes in ornithine may signify urea cycle issues contributing to increased BUN.
Xiaoyun Li, Xin Liu, Yingying Zhang, Jian Zhang, Xiaohui Gu, Yingying Zhang, Yingying Zhang, Yingying Zhang, Yingying Zhang, Yingying Zhang. Plasma Levels of Amino Acids Related to Urea Cycle and Risk of Type 2 Diabetes Mellitus in Chinese. PLOS ONE (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387924/
SDMA is a methylated form of arginine that is elevated in chronic kidney disease. It likely reflects overall kidney function similar to BUN.
Donald J. McCrann III, Rachel Murphy, Julie Cross, Marilyn Strong-Townsend, Corie Drake, Rebekah M. Mack, A. Eric Schultze. Evaluation of Renal Biomarkers, Including Symmetric Dimethylarginine, following Gentamicin-Induced Proximal Tubular Injury in the Rat. Kidney360 (2021). https://pubmed.ncbi.nlm.nih.gov/35622875/
Mark G. Lanz, Jody P. McLean, John R. Rush, and Linda C. Vogelnest. Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Cats with Chronic Kidney Disease. Journal of Veterinary Internal Medicine (2016). https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.13942
Alessandra Fascetti, Lisa K. Donnelly, and Greg Grauer. Assessment of Serum Symmetric Dimethylarginine and Creatinine Concentrations in Cats with Urethral Obstruction. Journal of Veterinary Emergency and Critical Care (2021). https://journals.sagepub.com/doi/full/10.1177/1098612X211060677
Michael J. Coyne, Donald J. McCrann III, Rachel Murphy, Julie Cross, Marilyn Strong-Townsend, Corie Drake, Rebekah M. Mack, A. Eric Schultze. Evaluation of Renal Injury and Function Biomarkers, Including Symmetric Dimethylarginine (SDMA), in the Rat Passive Heymann Nephritis (PHN) Model. PLoS ONE (2022). https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0269085
Juliana C. Silva, Maria G. Guilherme, Ana P. Santos, and Ana L. S. Santos. Symmetric Dimethylarginine Correlates with the Urea, Creatinine, Potassium, and Bicarbonate Levels in Cats with Urethral Obstruction. Frontiers in Veterinary Science (2024). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10990919/