Comparison of anamnestic and laboratory parameters in patients with different phenotypes of hyperuricemia (data from a pilot study)

Asymptomatic hyperuricemia (AHU) and gout are pathological conditions characterized by elevated uric acid (UA) levels in the blood. Gout is characterized by acute arthritis attacks due to UA crystallization in the joints. Other differences between AHU and gout require further study.

Study objective. To identify key differences between AHU phenotypes.

Materials and methods. 220 patients with HU (UA >360 μmol/L) over 18 years of age were examined and divided into the following phenotypes: AHU; AHU with monosodium urate crystals (verified by ultrasound or synovial fluid analysis) (AHU+crystals); intermittent gout (G); tophaceous gout (G+tophi). Comparative characteristics of the groups included an assessment of the frequency of comorbidities, metabolic disorders, and the main laboratory parameters.

Results. According to phenotyping results, the group of patients with AHU included 40 people (18.2%), AHU+crystals – 26 (11.8%), G – 111 (50.5%), G+tophi – 43 (19.5). The average age in the groups was comparable (p=0.5). An increase in the frequency of hypertension and nephrolithiasis was revealed in the series AHU without crystals – AHU+crystals – G – G+tophi (p=0.0006 and p=0.00006, respectively). Similar patterns were found for the mean serum levels of UA (p=0.00001), creatinine (p=0.0003), and GGT (p=0.0003), the mean values of which increased sequentially from AHU to G+tophi. The maximum mean levels of CRP were in patients with G and G+tophi (5.3 [2.3; 12.5] mg/L), which was significantly higher than in AHU patients (p=0.04). GFR was lower in the G+tophi group compared to AHU (74.7±20.0 ml/min/1.73m² vs 86.8±17.9 ml/min/1.73m² , respectively, p=0.02).

Conclusions. The incidence of hypertension, nephrolithiasis, serum GGT and creatinine levels increases as HU progresses from AGU to G+tophi, which may reflect the intensity of chronic microcrystalline inflammation.

1. Perez-Ruiz F., Dalbeth N., Bardin T. A review of uric acid, crystal deposition disease, and gout. Adv Ther. 2015; 32 (1): 31–41. https://doi.org/10.1007/s12325-014-0175-z

2. Dalbeth N., Stamp L. Hyperuricaemia and gout: time for a new staging system?. Ann Rheum Dis. 2014; 73 (9): 1598–1600. https://doi.org/10.1136/annrheumdis-2014-205304

3. Eliseev M.S, Eliseeva M.E. Modern Aspects of Pathogenesis and Correction of Hyperuricemia and Associated Conditions. Effektivnaya farmakoterapiya. 2019; 15 (8): 32–40. (In Russ.). https://doi.org/10.33978/2307-3586-2019-15-8-32-40

4. Freedman D.S., Williamson D.F., Gunter E.W., Byers T. Relation of serum uric acid to mortality and ischemic heart disease. The NHANES I Epidemiologic Follow-up Study. Am J Epidemiol. 1995; 141 (7): 637–644. https://doi.org/10.1093/oxfordjournals.aje.a117479

5. Li Y., Luo J., Liu X. et al. Association between change in serum uric acid and rapid decline in kidney function in China. Sci Rep. 2024; 14 (1): 25140. Published 2024 Oct 24. https://doi.org/10.1038/s41598-024-76398-7

6. Liu S., Sun H., Yang S. et al. Clustering of gout-related comorbidities and their relationship with gout flares: a data-driven cluster analysis of eight comorbidities. J Endocrinol Invest. 2024; 47 (5): 1119–1128. https://doi.org/10.1007/s40618-023-02224-y

7. Peral-Garrido M.L., Gómez-Sabater S., Caño R. et al. Systemic inflammation in asymptomatic hyperuricaemia with sonographic crystal deposits, including a comparison with normouricaemia and gout. Rheumatology (Oxford). 2025; 64 (4): 1807–1816. https://doi.org/10.1093/rheumatology/keae533

8. Kuo C.F., See L.C., Luo S.F. et al. Gout: an independent risk factor for all-cause and cardiovascular mortality. Rheumatology (Oxford). 2010; 49 (1): 141–146. https://doi.org/10.1093/rheumatology/kep364

9. Krishnan E. Interaction of inflammation, hyperuricemia, and the prevalence of hypertension among adults free of metabolic syndrome: NHANES2009–2010. J Am Heart Assoc. 2014; 3 (2): e000157. Published 2014 Mar 13. https://doi.org/10.1161/JAHA.113.000157

10. Maloberti A., Mengozzi A., Russo E. et al. The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation. High Blood Press Cardiovasc Prev. 2023; 30 (5): 411–425. https://doi.org/10.1007/s40292-023-00602-4

11. Ali N., Mahmood S., Islam F. et al. Relationship between serum uric acid and hypertension: a cross-sectional study in Bangladeshi adults. Sci Rep. 2019; 9 (1): 9061. Published 2019 Jun 21. https://doi.org/10.1038/s41598-019-45680-4

12. Bjornstad P., Laffel L., Lynch J. et al. Elevated Serum Uric Acid Is Associated With Greater Risk for Hypertension and Diabetic Kidney Diseases in Obese Adolescents With Type 2 Diabetes: An Observational Analysis From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study. Diabetes Care. 2019; 42 (6): 1120–1128. https://doi.org/10.2337/dc18-2147

13. Held J., Schwabl C., Haschka D. et al. Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques. Rheumatology (Oxford). 2025; 64 (3): 1443–1447. https://doi.org/10.1093/rheumatology/keae240

14. Markelova E.I., Eliseev M.S., Popkova T.V. et al. Prevalence and risk factors influencing the development of arterial hypertension in patients with a gout. Rheumatology Science and Practice. 2020; 58 (6): 701–707 (In Russ.). https://doi.org/10.47360/1995-4484-2020-701-707

15. Sapsford M., Gamble G.D., Aati O. et al. Relationship of bone erosion with the urate and soft tissue components of the tophus in gout: a dual energy computed tomography study. Rheumatology (Oxford). 2017; 56 (1): 129–133. https://doi.org/10.1093/rheumatology/kew383

16. Kramer H.J., Choi H.K., Atkinson K. et al. The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study. Kidney Int. 2003; 64 (3): 1022–1026. https://doi.org/10.1046/j.1523–1755.2003.t01-2-00171.x

17. Roughley M.J., Belcher J., Mallen C.D., Roddy E. Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies. Arthritis Res Ther. 2015; 17 (1): 90. Published 2015 Apr 1. https://doi.org/10.1186/s13075-015-0610-9

18. Kim S., Chang Y., Yun K. E. et al. Development of Nephrolithiasis in Asymptomatic Hyperuricemia: A Cohort Study. Am J Kidney Dis. 2017; 70 (2): 173–181. https://doi.org/10.1053/j.ajkd.2017.01.053

19. Ramos G.K., Goldfarb D.S. Update on Uric Acid and the Kidney. Curr Rheumatol Rep. 2022; 24 (5): 132–138. https://doi.org/10.1007/s11926-022-01069-3

20. KC M., Leslie S.W. Uric Acid Nephrolithiasis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; October 15, 2023.

21. Bardin T., Letavernier E., Correas J.-M. The Gouty Kidney: A Reappraisal. Gout, Urate, and Crystal Deposition Disease. 2023; 1 (1): 25–36. https://doi.org/10.3390/gucdd1010004

22. Sellmayr M., Hernandez Petzsche M.R., Ma Q. et al. Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease. J Am Soc Nephrol. 2020; 31 (12): 2773–2792. https://doi.org/10.1681/ASN.2020040523

23. Ruggiero C., Cherubini A., Ble A. et al. Uric acid and inflammatory markers. Eur Heart J. 2006; 27 (10): 1174–1181. https://doi.org/10.1093/eurheartj/ehi879

24. Liu W., Song H., Man S. et al. Simple metabolic markers associated with tophaceous gout. Clin Rheumatol. 2021; 40 (12): 5047–5053. https://doi.org/10.1007/s10067-021-05861-x

25. Eliseev M.S., Zheliabina O.V., Panina E.V. Factors affecting the frequency of arthritis attacks in patients with gout not receiving urate-lowering therapy (results of a pilot retrospective study). Rheumatology Science and Practice. 2024; 62 (3): 280–285 (In Russ.). https://doi.org/10.47360/1995-4484-2024-280-285