Child Kidney Dis.  2024 Oct;28(3):106-111. 10.3339/ckd.24.016.

Association between serum uric acid and kidney disease with pediatric focus

• Cho MH

• KMID: 2560479
• DOI: http://doi.org/10.3339/ckd.24.016

Abstract

Hyperuricemia is a global medical issue. Kidney disease and hyperuricemia are clearly related. Whether uric acid is a disease bystander or a therapeutic target in chronic kidney disease (CKD) remains controversial. Uric acid is involved in various mechanisms that worsen kidney function, and many epidemiological and animal studies have shown an association between hyperuricemia and kidney deterioration. However, several confounding variables limit this interpretation of the relationship. Two recent large well-designed studies failed to show that allopurinol, a uric acid-lowering agent, slows the decline in glomerular filtration rate. Nevertheless, this conclusion remains premature. The role of uric acid-lowering agents in delaying disease progression in patients with early-stage CKD, such as pediatric patients, requires further study.

Keyword

Child; Hyperuricemia; Renal insufficiency, chronic; Uric acid

Reference

References

1. Ames BN, Cathcart R, Schwiers E, Hochstein P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci U S A. 1981; 78:6858–62.

2. Alvarez-Lario B, Macarron-Vicente J. Uric acid and evolution. Rheumatology (Oxford). 2010; 49:2010–5.

3. Roman YM. The role of uric acid in human health: insights from the Uricase gene. J Pers Med. 2023; 13:1409.

4. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007-2008. Arthritis Rheum. 2011; 63:3136–41.

5. Fishberg AM. The interpretation of increased blood uric acid in hypertension. Arch Intern Med. 1924; 34:503–7.

6. Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Contemporary prevalence of gout and hyperuricemia in the United States and decadal trends: the National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheumatol. 2019; 71:991–9.

7. Copur S, Demiray A, Kanbay M. Uric acid in metabolic syndrome: does uric acid have a definitive role? Eur J Intern Med. 2022; 103:4–12.

8. Bardin T, Richette P. Definition of hyperuricemia and gouty conditions. Curr Opin Rheumatol. 2014; 26:186–91.

9. Chen JH, Yeh WT, Chuang SY, Wu YY, Pan WH. Gender-specific risk factors for incident gout: a prospective cohort study. Clin Rheumatol. 2012; 31:239–45.

10. Cho MH, Kim YM, Yoon JH, Kim DH, Lim JS. Serum uric acid in Korean children and adolescents: reference percentiles and association with metabolic syndrome. Ann Pediatr Endocrinol Metab. 2020; 25:104–11.

11. Kumar J, Gupta A, Dev K, Kumar S, Kataria D, Gul A, et al. Prevalence and causes of hyperuricemia in children. Cureus. 2021; 13:e15307.

12. Kliegman R, St. Geme JW. III. Nelson textbook of pediatrics. 21st ed. Elsevier;2019.

13. Su HY, Yang C, Liang D, Liu HF. Research advances in the mechanisms of hyperuricemia-induced renal injury. Biomed Res Int. 2020; 2020:5817348.

14. Ahmad MI, Masood S, Furlanetto DM, Nicolaou S. Urate crystals; beyond joints. Front Med (Lausanne). 2021; 8:649505.

15. Yang L, Chang B, Guo Y, Wu X, Liu L. The role of oxidative stress-mediated apoptosis in the pathogenesis of uric acid nephropathy. Ren Fail. 2019; 41:616–22.

16. Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005; 67:237–47.

17. Domrongkitchaiporn S, Sritara P, Kitiyakara C, Stitchantrakul W, Krittaphol V, Lolekha P, et al. Risk factors for development of decreased kidney function in a southeast Asian population: a 12-year cohort study. J Am Soc Nephrol. 2005; 16:791–9.

18. Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008; 19:1204–11.

19. Ben-Dov IZ, Kark JD. Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study. Nephrol Dial Transplant. 2011; 26:2558–66.

20. Hsu CY, Iribarren C, McCulloch CE, Darbinian J, Go AS. Risk factors for end-stage renal disease: 25-year follow-up. Arch Intern Med. 2009; 169:342–50.

21. Rodenbach KE, Schneider MF, Furth SL, Moxey-Mims MM, Mitsnefes MM, Weaver DJ, et al. Hyperuricemia and progression of CKD in children and adolescents: the chronic kidney disease in children (CKiD) cohort study. Am J Kidney Dis. 2015; 66:984–92.

22. Schwartz GJ, Roem JL, Hooper SR, Furth SL, Weaver DJ Jr, Warady BA, et al. Longitudinal changes in uric acid concentration and their relationship with chronic kidney disease progression in children and adolescents. Pediatr Nephrol. 2023; 38:489–97.

23. Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002; 13:2888–97.

24. Kojima S, Matsui K, Hiramitsu S, Hisatome I, Waki M, Uchiyama K, et al. Febuxostat for cerebral and cardiorenovascular events prevention study. Eur Heart J. 2019; 40:1778–86.

25. Ghane Sharbaf F, Assadi F. Effect of allopurinol on the glomerular filtration rate of children with chronic kidney disease. Pediatr Nephrol. 2018; 33:1405–9.

26. Liu P, Chen Y, Wang B, Zhang F, Wang D, Wang Y. Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study. Clin Endocrinol (Oxf). 2015; 83:475–82.

27. Doria A, Galecki AT, Spino C, Pop-Busui R, Cherney DZ, Lingvay I, et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med. 2020; 382:2493–503.

28. Badve SV, Pascoe EM, Tiku A, Boudville N, Brown FG, Cass A, et al. Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med. 2020; 382:2504–13.

29. Leoncini G, Barnini C, Manco L, Nobili G, Dotta D, Penso M, et al. Uric acid lowering for slowing CKD progression after the CKD-FIX trial: a solved question or still a dilemma? Clin Kidney J. 2022; 15:1666–74.

30. Kimura K, Hosoya T, Uchida S, Inaba M, Makino H, Maruyama S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis. 2018; 72:798–810.

31. Kataoka H, Mochizuki T, Ohara M, Tsuruta Y, Iwasa N, Yoshida R, et al. Urate-lowering therapy for CKD patients with asymptomatic hyperuricemia without proteinuria elucidated by attribute-based research in the FEATHER Study. Sci Rep. 2022; 12:3784.

32. Lima WG, Martins-Santos ME, Chaves VE. Uric acid as a modulator of glucose and lipid metabolism. Biochimie. 2015; 116:17–23.

33. Nguyen S, Choi HK, Lustig RH, Hsu CY. Sugar-sweetened beverages, serum uric acid, and blood pressure in adolescents. J Pediatr. 2009; 154:807–13.

34. Malik VS, Schulze MB, Hu FB. Intake of sugar-sweetened beverages and weight gain: a systematic review. Am J Clin Nutr. 2006; 84:274–88.

35. Kazancioglu R. Risk factors for chronic kidney disease: an update. Kidney Int Suppl (2011). 2013; 3:368–71.

36. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024; 105(4S):S117–314.

37. FitzGerald JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM, et al. 2020 American College of Rheumatology Guideline for the management of gout. Arthritis Rheumatol. 2020; 72:879–95.

38. Hisatome I, Ichida K, Mineo I, Ohtahara A, Ogino K, Kuwabara M, et al. Japanese Society of Gout and Uric & Nucleic Acids 2019 guidelines for management of hyperuricemia and gout 3rd edition. Gout Uric Nucleic Acids. 2020; 44(Suppl):sp-1–40.

39. Lee JJ, Lee JS, Chung MK, Ahn JK, Choi HJ, Hong SJ, et al. Korean guidelines for the management of gout. Korean J Intern Med. 2023; 38:641–50.

40. Feig DI. The role of uric acid in the pathogenesis of hypertension in the young. J Clin Hypertens (Greenwich). 2012; 14:346–52.