Characterizing the Association Between Blood Urea Nitrogen Levels within the Normal Range and Thyroid Function Among US Adults: NHANES 2007–2012 Findings

Abstract

Blood urea nitrogen (BUN) is a key metric when evaluating the renal function of a given patient. Individuals with chronic kidney disease also often present with abnormal thyroid functionality. The specific association between BUN and thyroid function, however, is not well understood. This study was thus developed to explore how BUN levels within the normal range are related to thyroid activity among adults in the USA. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged for these analyses. Linear regression and smoothed curve fitting approaches were employed to examine the association between BUN levels and measures of thyroid function, with appropriate weighted and subgroup analyses. The 2007–2012 NHANEs cycles included 6231 eligible adults with BUN levels from 2.5–8.0 mmol/l. Under adjusted models, a higher BUN level was associated with reductions in FT3 (β=–0.01; p=0.047), TT3 (β=–1.08; p=0.003), and TT4 (β=–0.10; p=0.003) levels. In subgroup analyses, BUN levels were respectively found to be negatively correlated with FT3 and TT4 levels in subjects who were inactive and active. These findings are consistent with reduced FT3, TT4, and TT4 levels being correlated with higher BUN levels within the normal range among American adults. In non-physically active subjects, FT3 levels were more closely related to increasing BUN levels, whereas TT4 levels were more closely related to BUN levels among physically active subjects. However, additional research will be vital to clarify the mechanisms that underlie these results.

Keywords

thyroid function - blood urea nitrogen - NHANES - kidney function

Publication History

Received: 17 November 2023

Accepted after revision: 14 December 2024

Article published online:
10 February 2025

• References

• 1 Dossetor JB. Creatininemia versus uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann Intern Med 1966; 65: 1287-1299
• 2 Beier K, Eppanapally S, Bazick HS. et al. Elevation of blood urea nitrogen is predictive of long-term mortality in critically ill patients independent of “normal” creatinine. Crit Care Med 2011; 39: 305-313
• 3 Peng R, Liu K, Li W. et al. Blood urea nitrogen, blood urea nitrogen to creatinine ratio and incident stroke: The Dongfeng-Tongji cohort. Atherosclerosis 2021; 333: 1-8
• 4 Fenton RA. Essential role of vasopressin-regulated urea transport processes in the mammalian kidney. Pflugers Arch Eur J Physiol 2009; 458: 169-177
• 5 Lindenfeld J, Schrier RW. Blood urea nitrogen a marker for adverse effects of loop diuretics?. J Am Coll Cardiol 2011; 58: 383-385
• 6 Du J, Niu J, Ma L. et al. Association between blood urea nitrogen levels and length of stay in patients with pneumonic chronic obstructive pulmonary disease exacerbation: a secondary analysis based on a multicentre, retrospective cohort study. Int J Chronic Obstr Pulmon Dis 2022; 17: 2847-2856
• 7 You S, Zheng D, Zhong C. et al. Prognostic significance of blood urea nitrogen in acute ischemic stroke. Circul J 2018; 82: 572-578
• 8 Xie Y, Bowe B, Li T. et al. Blood urea nitrogen and risk of insulin use among people with diabetes. Diabetes Vasc Dis Res 2018; 15: 409-416
• 9 Smith GL, Lichtman JH, Bracken MB. et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 2006; 47: 1987-1996
• 10 Jujo K, Minami Y, Haruki S. et al. Persistent high blood urea nitrogen level is associated with increased risk of cardiovascular events in patients with acute heart failure. ESC Heart Fail 2017; 4: 545-553
• 11 Smilde TD, Damman K, van der Harst P. et al. Differential associations between renal function and “modifiable” risk factors in patients with chronic heart failure. Clin Res Cardiol 2009; 98: 121-129
• 12 Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev 2001; 81: 1097-1142
• 13 Mariani LH, Berns JS. The renal manifestations of thyroid disease. J Am Soc Nephrol 2012; 23: 22-26
• 14 Kumar J, Gordillo R, Kaskel FJ. et al. Increased prevalence of renal and urinary tract anomalies in children with congenital hypothyroidism. J Pediatr 2009; 154: 263-266
• 15 Zimmerman RS, Ryan J, Edwards BS. et al. Cardiorenal endocrine dynamics during volume expansion in hypothyroid dogs. Am J Physiol 1988; 255: R61-R66
• 16 Khatiwada S, Rajendra KC, Gautam S. et al. Thyroid dysfunction and dyslipidemia in chronic kidney disease patients. BMC Endocr Disord 2015; 15: 65
• 17 Naguib R, Elkemary E. Thyroid dysfunction and renal function: a crucial relationship to recognize. Cureus 2023; 15: e35242
• 18 Park S, Kim WG, Jeon MJ. et al. Serum thyroid-stimulating hormone levels and smoking status: Data from the Korean national health and nutrition examination survey VI. Clin Endocrinol 2018; 88: 969-976
• 19 Thavaraputta S, Dennis JA, Laoveeravat P. et al. Hypothyroidism and its association with sleep apnea among adults in the United States: NHANES 2007-2008. J Clin Endocrinol Metab 2019; 104: 4990-4997
• 20 Levey AS, Stevens LA, Schmid CH. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612
• 21 Yang W, Huang S, Xiao H. et al. Association of frailty and serum neurofilament light chain levels: the mediating role of estimated glomerular filtration rate. Front Aging Neurosci 2024; 16: 1475505
• 22 Mirel LB, Mohadjer LK, Dohrmann SM. et al. National health and nutrition examination survey: estimation procedures, 2007-2010. Vital Health Statistics Series 2, Data Eval Meth Res 2013; 159: 1-17
• 23 Chen TC, Parker JD, Clark J. et al. National health and nutrition examination survey: estimation procedures, 2011–2014. Vital Health Statistics Series 2, Data Eval Meth Res 2018; 177: 1-26
• 24 Iglesias P, Díez JJ. Thyroid dysfunction and kidney disease. Eur J Endocrinol 2009; 160: 503-515
• 25 Kimmel M, Braun N, Alscher MD. Influence of thyroid function on different kidney function tests. Kidney Blood Press Res 2012; 35: 9-17
• 26 Panicker V, Wilson SG, Spector TD. et al. Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort. Clin Endocrinol 2008; 68: 652-659
• 27 Chaker L, Korevaar TI, Medici M. et al. Thyroid function characteristics and determinants: the Rotterdam study. Thyroid 2016; 26: 1195-1204
• 28 Helmreich DL, Parfitt DB, Lu XY. et al. Relation between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-adrenal (HPA) axis during repeated stress. Neuroendocrinology 2005; 81: 183-192
• 29 Montanelli L, Benvenga S, Hegedüs L. et al. Drugs and other substances interfering with thyroid function. 2018
• 30 Zimmermann MB. Iodine deficiency. Endocr Rev 2009; 30: 103-111
• 31 Lo JC, Chertow GM, Go AS. et al. Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int 2005; 67: 1047-1052
• 32 Rhee CM, Kalantar-Zadeh K, Streja E. et al. The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease. Nephrol Dialysis Transplant 2015; 30: 282-287
• 33 Iglesias P, Bajo MA, Selgas R. et al. Thyroid dysfunction and kidney disease: an update. Rev Endocr Metab Disord 2017; 18: 131-144
• 34 Dousdampanis P, Trigka K, Vagenakis GA. et al. The thyroid and the kidney: a complex interplay in health and disease. Int J Artif Organs 2014; 37: 1-12
• 35 Kumari B, Kumar P, Keshari JR. et al. Serum BUN and creatinine estimation in patients of overt hypothyroidism: a case control study. Int J Res Med Sci 2017; 5: 3990-3993
• 36 Li H, Miao X. Prediction of thyroid hormone level on risk of type 2 diabetes nephropathy. Clinl Focus 2023; 38: 137-142
• 37 Xue X, Ren W, Yan F. et al. Urine PH Level of Patients with Hyperuricemia and its influencing factors. J Qingdao Uni (Med Sci) 2020; 56: 576-579
• 38 Liu Q, Wang Y, Chen Z. et al. Age- and sex-specific reference intervals for blood urea nitrogen in Chinese general population. Sci Rep 2021; 11: 10058
• 39 Jensen E, Blaabjerg O, Petersen PH. et al. Sampling time is important but may be overlooked in establishment and use of thyroid-stimulating hormone reference intervals. Clin Chem 2007; 53: 355-356