Association of uric acid in serum and urine with subclinical renal damage: Hanzhong Adolescent Hypertension Study

Autoři: Yang Wang aff001;  Chen Chen aff001;  Yu Yan aff001;  Yue Yuan aff001;  Ke-Ke Wang aff001;  Chao Chu aff001;  Jia-Wen Hu aff001;  Qiong Ma aff001;  Yue-Yuan Liao aff001;  Bo-Wen Fu aff001;  Ke Gao aff001;  Yue Sun aff001;  Yong-Bo Lv aff003;  Wen-Jing Zhu aff001;  Lei Yang aff001;  Jie Zhang aff004;  Rui-Hai Yang aff005;  Jun Yang aff005;  Jian-Jun Mu aff001
Působiště autorů: Department of Cardiovascular Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China aff001;  Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi’an, China aff002;  Department of Cardiology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China aff003;  Department of Cardiology, Xi’an Fourth People’s Hospital, Xi’an, China aff004;  Institute of Cardiovascular Sciences, Hanzhong People’s Hospital, Hanzhong, China aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224680


Background and objectives

The aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort.


1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline.


In cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255–5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline.


This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.

Klíčová slova:

Creatinine – Excretion – Glomerular filtration rate – Hypertension – Cholesterol – Urine – Uric acid


1. Schieppati A, Remuzzi G Chronic renal diseases as a public health problem: epidemiology, social, and economic implications. Kidney Int Suppl. 2005; (98): S7–7S10. 16108976

2. Weiner DE, Tighiouart H, Amin MG, Stark PC, MacLeod B, Griffith JL, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol. 2004; 15(5): 1307–15. doi: 10.1097/01.asn.0000123691.46138.e2 15100371

3. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012; 379(9818): 815–22. 22386035

4. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007; 298(17): 2038–47. 17986697

5. Prasad SOS, Qing YX Associations Between Hyperuricemia and Chronic Kidney Disease: A Review. Nephrourol Mon. 2015; 7(3): e27233. 26290849

6. Wang Y, Hu JW, Lv YB, Chu C, Wang KK, Zheng WL, et al. The Role of Uric Acid in Hypertension of Adolescents, Prehypertension and Salt Sensitivity of Blood Pressure. Med Sci Monit. 2017; 23790–5. doi: 10.12659/MSM.899563 28190873

7. Lippi G, Montagnana M, Franchini M, Favaloro EJ, Targher G The paradoxical relationship between serum uric acid and cardiovascular disease. Clin Chim Acta. 2008; 392(1–2): 1–7. 18348869

8. Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M, et al. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010; 25(6): 1865–9. 20064950

9. Feig DI, Kang DH, Johnson RJ Uric acid and cardiovascular risk. N Engl J Med. 2008; 359(17): 1811–21. 18946066

10. Scheven L, Joosten MM, de Jong PE, Bakker SJ, Gansevoort RT The association of albuminuria with tubular reabsorption of uric acid: results from a general population cohort. J Am Heart Assoc. 2014; 3(2): e000613. doi: 10.1161/JAHA.113.000613 24772520

11. Wang J, Yu Y, Li X, Li D, Xu C, Yuan J, et al. Serum uric acid levels and decreased estimated glomerular filtration rate in patients with type 2 diabetes: A cohort study and meta-analysis. Diabetes Metab Res Rev. 2018; 34(7): e3046. 30003679

12. Xu Y, Liu X, Sun X, Wang Y The impact of serum uric acid on the natural history of glomerular filtration rate: a retrospective study in the general population. PeerJ. 2016; 4 e1859. 27069799

13. Viazzi F, Leoncini G, Ratto E, Falqui V, Parodi A, Conti N, et al. Mild hyperuricemia and subclinical renal damage in untreated primary hypertension. Am J Hypertens. 2007; 20(12): 1276–82. 18047917

14. Mule G, Calcaterra I, Costanzo M, Geraci G, Guarino L, Foraci AC, et al. Relationship Between Short-Term Blood Pressure Variability and Subclinical Renal Damage in Essential Hypertensive Patients. J Clin Hypertens (Greenwich). 2015; 17(6): 473–80. 25808042

15. Hayashino Y, Okamura S, Tsujii S, Ishii H Association of serum uric acid levels with the risk of development or progression of albuminuria among Japanese patients with type 2 diabetes: a prospective cohort study [Diabetes Distress and Care Registry at Tenri (DDCRT 10)]. Acta Diabetol. 2016; 53(4): 599–607. 26935413

16. Forman JP, Scheven L, de Jong PE, Bakker SJ, Curhan GC, Gansevoort RT Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension. Circulation. 2012; 125(25): 3108–16. 22711274

17. Lytvyn Y, Perkins BA, Cherney DZI Uric acid as a biomarker and a therapeutic target in diabetes. Can J Diabetes. 2015; 39(3): 239–46. doi: 10.1016/j.jcjd.2014.10.013 25600084

18. Coe FL, Kavalach AG Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis. N Engl J Med. 1974; 291(25): 1344–50. 4610395

19. Coe FL Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria, or no metabolic disorder. Ann Intern Med. 1977; 87(4): 404–10. doi: 10.7326/0003-4819-87-4-404 907239

20. Nariman S, Mosayebi Z, Sagheb S, Rastad H, Hosseininodeh SS Urinary Uric Acid/Creatinine Ratio as a Marker of Mortality and Unfavorable Outcome in NICU-Admitted Neonates. Iran J Pediatr. 2016; 26(4): e5739. 27729961

21. Chen HJ, Yau KI, Tsai KS Urinary uric acid/creatinine ratio as an additional marker of perinatal asphyxia. J Formos Med Assoc. 2000; 99(10): 771–4. 11061072

22. Gane Bahubali D, Bhat Vishnu B, Ramachandra R, Adhisivam B, Rojo J, Prasad P, et al. Biochemical marker as predictor of outcome in perinatal asphyxia. Current Pediatric Research. 2013; 17(2).

23. Wang Y, Hu JW, Qu PF, Wang KK, Yan Y, Chu C, et al. Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults. Sci Rep. 2018; 8(1): 7749. 29773847

24. Zheng W, Mu J, Chu C, Hu J, Yan Y, Ma Q, et al. Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age. J Am Soc Nephrol. 2018; 29(12): 2835–46. 30420422

25. Wang Y, Lv YB, Chu C, Wang M, Xie BQ, Wang L, et al. Plasma Renalase is Not Associated with Blood Pressure and Brachial-Ankle Pulse Wave Velocity in Chinese Adults With Normal Renal Function. Kidney Blood Press Res. 2016; 41(6): 837–47. 27871085

26. Wang Y, Yuan Y, Gao WH, Yan Y, Wang KK, Qu PF, et al. Predictors for progressions of brachial-ankle pulse wave velocity and carotid intima-media thickness over a 12-year follow-up: Hanzhong Adolescent Hypertension Study. J Hypertens. 2019; 37(6): 1167–75. 31026243

27. Wang Y, Wang D, Chu C, Mu JJ, Wang M, Liu FQ, et al. Effect of Salt Intake and Potassium Supplementation on Urinary Renalase and Serum Dopamine Levels in Chinese Adults. Cardiology. 2015; 130(4): 242–8. 25824645

28. Wang Y, Chu C, Wang KK, Hu JW, Yan Y, Lv YB, et al. Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults: An Interventional Trial. Sci Rep. 2018; 8(1): 1434. 29362390

29. Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol. 2006; 17(10): 2937–44. 16988059

30. Maesaka JK, Fishbane S Regulation of renal urate excretion: a critical review. Am J Kidney Dis. 1998; 32(6): 917–33. doi: 10.1016/s0272-6386(98)70067-8 9856507

31. Lipkowitz MS Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012; 14(2): 179–88. 22359229

32. Leoncini G, Viazzi F, Conti N, Baratto E, Tomolillo C, Bezante GP, et al. Renal and cardiac abnormalities in primary hypertension. J Hypertens. 2009; 27(5): 1064–73. 19357534

33. Bobulescu IA, Moe OW Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis. 2012; 19(6): 358–71. 23089270

34. Verzola D, Ratto E, Villaggio B, Parodi EL, Pontremoli R, Garibotto G, et al. Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One. 2014; 9(12): e115210. 25514209

35. Milanesi S, Verzola D, Cappadona F, Bonino B, Murugavel A, Pontremoli R, et al. Uric acid and angiotensin II additively promote inflammation and oxidative stress in human proximal tubule cells by activation of toll-like receptor 4. J Cell Physiol. 2019; 234(7): 10868–76. 30536556

36. Akasaka H, Yoshida H, Takizawa H, Hanawa N, Tobisawa T, Tanaka M, et al. The impact of elevation of serum uric acid level on the natural history of glomerular filtration rate (GFR) and its sex difference. Nephrol Dial Transplant. 2014; 29(10): 1932–9. 24891435

37. De Cosmo S, Viazzi F, Pacilli A, Giorda C, Ceriello A, Gentile S, et al. Serum Uric Acid and Risk of CKD in Type 2 Diabetes. Clin J Am Soc Nephrol. 2015; 10(11): 1921–9. 26342044

38. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31(7): 1281–357. 23817082

39. Ozyilmaz A, de Jong PE, SJL B, Visser ST, Thio C, Gansevoort RT Screening for elevated albuminuria and subsequently hypertension identifies subjects in which treatment may be warranted to prevent renal function decline. Nephrol Dial Transplant. 2017; 32(suppl_2): ii200–200ii208. 28031343

40. Cerasola G, Cottone S, Mule G The progressive pathway of microalbuminuria: from early marker of renal damage to strong cardiovascular risk predictor. J Hypertens. 2010; 28(12): 2357–69. 20842046

41. Momeni A, Shahidi S, Seirafian S, Taheri S, Kheiri S Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients. Iran J Kidney Dis. 2010; 4(2): 128–32. 20404423

42. Li F, Guo H, Zou J, Chen W, Lu Y, Zhang X, et al. Urinary excretion of uric acid is negatively associated with albuminuria in patients with chronic kidney disease: a cross-sectional study. BMC Nephrol. 2018; 19(1): 95. 29699501

43. Zou H, Xiang M, Ye X, Xiong Y, Xie B, Shao J Reduction of urinary uric acid excretion in patients with proteinuria. J Chromatogr B Analyt Technol Biomed Life Sci. 2015; 100659–64. 26523664

44. Zelmanovitz T, Gross JL, Oliveira JR, Paggi A, Tatsch M, Azevedo MJ The receiver operating characteristics curve in the evaluation of a random urine specimen as a screening test for diabetic nephropathy. Diabetes Care. 1997; 20(4): 516–9. doi: 10.2337/diacare.20.4.516 9096972

45. Nathan DM, Rosenbaum C, Protasowicki VD Single-void urine samples can be used to estimate quantitative microalbuminuria. Diabetes Care. 1987; 10(4): 414–8. doi: 10.2337/diacare.10.4.414 3622198

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