Salivary Uric Acid as a Non-Invasive Biomarker in Hypertensive Patients: A Comparative Cross-Sectional Study

Background. Hypertension is a leading global cause of cardiovascular morbidity and mortality. Uric acid (UA) is implicated in oxidative stress, endothelial dysfunction, and hypertensive pathophysiology. Salivary UA offers a non-invasive, cost-effective alternative to serum analysis.

Aim: To compare salivary UA levels in hypertensive adults against normotensive controls and evaluate its diagnostic utility.

Material and Methods. This prospective case-control study enrolled 60 adult hypertensive patients and 60 age- and sex-matched normotensive controls. Non-stimulated whole saliva (NWS) and stimulated whole saliva (SWS) were collected following a standardised protocol. Salivary UA concentrations were measured spectrophotometrically using a commercial QuantiChrom™ Uric Acid Assay Kit. Serum UA, total antioxidant capacity (TAC), and salivary flow rates were also assessed. Pearson correlation coefficients and receiver operating characteristic (ROC) analysis were applied for statistical evaluation.

Results. SWS UA was significantly higher in the hypertensive group (18.62 ± 3.27 µg/mg protein) versus controls (6.14 ± 1.92 µg/mg protein; p < 0.001). NWS UA was similarly elevated. Salivary UA in SWS correlated positively with systolic blood pressure (r = 0.79, p < 0.001), diastolic blood pressure (r = 0.81, p < 0.001), and serum UA (r = 0.84, p < 0.001). ROC analysis showed SWS UA had an AUC of 0.97 with sensitivity of 92% and specificity of 93% in differentiating hypertensive from normotensive individuals. Stimulated salivary flow was significantly lower in the hypertensive group.

Conclusion. Salivary UA, particularly measured in stimulated saliva, is markedly elevated in hypertensive patients and demonstrates strong diagnostic performance. It represents a promising non-invasive biomarker for hypertension screening and monitoring, warranting validation in larger multicentre studies.

1. Poulter N.R., Prabhakaran D., Caulfield M. Hypertension. Lancet. 2015;386(9995):801–812. DOI: 10.1016/S0140-6736(14)61468-9

2. Glantzounis G.K., Tsimoyiannis E.C., Kappas A.M., Galaris D.A. Uric acid and oxidative stress. Curr. Pharm. Des. 2005;11(32):4145–4151. DOI: 10.2174/138161205774913255

3. Bainbridge S.A., Roberts J.M. Uric acid as a pathogenic factor in preeclampsia. Placenta. 2008;29(Suppl. A):S67–72. DOI: 10.1016/j.placenta.2007.11.001

4. Colmenares-Mejia C.C., Quintero-Lesmes D.C., Bautista-Niño P.K., et al. Uric acid and risk of pre-eclampsia: results from a large case-control study and meta-analysis of prospective studies. Sci. Rep. 2023;13(1):3018. DOI: 10.1038/s41598-023-29651-4

5. Liu J., Duan Y. Saliva: a potential media for disease diagnostics and monitoring. Oral. Oncol. 2012;48(7):569–577. DOI: 10.1016/j.oraloncology.2012.01.021

6. Jaiswal A., Madaan S., Acharya N., et al. Salivary uric acid: a noninvasive wonder for clinicians? Cureus. 2021;13(11):e19649. DOI: 10.7759/cureus.19649

7. Wang Q., Wen X., Kong J. Recent progress on uric acid detection: a review. Crit. Rev. Anal. Chem. 2020;50(4):359–375. DOI: 10.1080/10408347.2019.1637711

8. Vernerová A., Kujovská Krčmová L., Melichar B., Švec F. Non-invasive determination of uric acid in human saliva in the diagnosis of serious disorders. Clin. Chem. Lab. Med. 2020;59(5):797–812. DOI: 10.1515/cclm-2020-1533

9. Maciejczyk M., Taranta-Janusz K., Wasilewska A., et al. A case-control study of salivary redox homeostasis in hypertensive children. Can salivary uric acid be a marker of hypertension? J. Clin. Med. 2020;9(3):837. DOI: 10.3390/jcm9030837

10. Chmielewska B., Reading I., Bhide A., et al. Validation of salivary uric acid remote self-monitoring for early prediction of hypertensive disorders of pregnancy: study protocol for a prospective, observational, multicentre cohort study. BMJ Open. 2025;15:e094421. DOI: 10.1136/bmjopen-2024-094421

11. Mancia G., Kreutz R., Brunström M., et al. 2023 ESH Guidelines for the management of arterial hypertension. J. Hypertens. 2023;41(12):1874– 2071. DOI: 10.1097/hjh.0000000000003480

12. Kamodyová N., Tóthová L., Celec P. Salivary markers of oxidative stress and antioxidant status: influence of external factors. Dis. Markers. 2013;34(5):313–21. DOI: 10.3233/DMA-130975

13. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin. Biochem. 2004;37(4):277–285. DOI: 10.1016/j.clinbiochem.2003.11.015

14. Zukowski P., Maciejczyk M., Waszkiel D. Sources of free radicals and oxidative stress in the oral cavity. Arch. Oral. Biol. 2018;92:8–17. DOI: 10.1016/j.archoralbio.2018.04.018

15. Gersch C., Palii S.P., Imaram W., et al. Reactions of peroxynitrite with uric acid: formation of reactive intermediates, alkylated products and triuret, and in vivo production of triuret under conditions of oxidative stress. Nucleosides Nucleotides Nucleic. Acids. 2009;28(2):118–149. DOI: 10.1080/15257770902736400

16. Shibasaki K., Kimura M., Ikarashi R., et al. Uric acid concentration in saliva and its changes with the patients receiving treatment for hyperuricemia. Metabolomics. 2012;8(3):484–491. DOI: 10.1007/s11306-011-0334-z

17. Zhao J., Huang Y. Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy. Clin. Chim. Acta. 2015;450:115–120. DOI: 10.1016/j.cca.2015.08.005

18. Proctor G.B., Carpenter G.H. Regulation of salivary gland function by autonomic nerves. Auton. Neurosci. 2007;133(1):3–18. DOI: 10.1016/j.cca.2015.08.005

19. Stolbikova M.E., Gaydukova I.Z., Sapozhnikov G.A., et al. Salivary uric acid as a biomarker for noninvasive diagnosis of diseases associated with purine metabolism disorder and methods for its determination. Russian Medical Inquiry. 2025;9(3):167–174. (In Russ.). DOI: 10.32364/2587-6821-2025-9-3-4 EDN: UXQRAT