International Urology and Nephrology

, Volume 51, Issue 12, pp 2227–2233 | Cite as

Treatment of asymptomatic hyperuricemia complicated by renal damage: a controversial issue

  • Chun Hu
  • Xiaoyan WuEmail author
Nephrology - Review


The prevalence of asymptomatic HUA is increasing year after year. HUA is a risk factor for the occurrence and development of renal diseases. However, the role of urate-lowering therapy in asymptomatic HUA complicated by renal damage is still controversial. In some experiments, the treatment of asymptomatic HUA complicated by renal damage may delay the progression of kidney damage. In addition, there is increasing evidence, suggesting that elevated serum uric acid is an independent risk factor for kidney disease. However, in other studies, uric acid-lowering therapy did not improve renal function, and uric acid levels could not be used as an independent predictor for CKD development. Further experimental studies are needed to determine the starting threshold and target value of asymptomatic HUA complicated by renal damage. At the same time, confirmation of the benefits of urate-lowering therapy for kidneys requires studies with larger samples and high-quality RCTs.


Asymptomatic HUA Urate-lowering therapy Renal damage 



This work was supported by fundamental research funds for central universities (2042018kf0142).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


  1. 1.
    Saag KG, Choi H (2006) Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther 8(Suppl. 1):S2PubMedPubMedCentralGoogle Scholar
  2. 2.
    Richette P, Bardin T (2010) Gout. Lancet 375(9711):318–328PubMedGoogle Scholar
  3. 3.
    Lin KC, Lin HY, Chou P (2000) Community based epidemiological study on hyperuricemia and gout in Kin-Hu, Kinmen. J Rheumatol 27(4):1045PubMedGoogle Scholar
  4. 4.
    Johnson RJ et al (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension 41(6):1183–1190PubMedGoogle Scholar
  5. 5.
    Esparza Martín N, García Nieto V (2011) Hypouricemia and tubular transport of uric acid. Nefrologia 31(1):44–50. CrossRefPubMedGoogle Scholar
  6. 6.
    Einollahi B, Einollahi H, Rostami Z (2011) Elderlyrenal transplant recipients and renal dysfunction: a risk factor for hyperuricemia. Exp Clin Transpl 9(6):376-38Google Scholar
  7. 7.
    Johnson RJ et al (2005) Resurrection of uric acid as a causal risk factor in essential hypertension. Hypertension 45(1):28Google Scholar
  8. 8.
    Satirapoj B et al (2011) High levels of uric acid correlate with decline of glomerular filtration rate in chronic kidney disease. J Med Assoc Thai 93(suppl 6):S65–S70Google Scholar
  9. 9.
    Ben-Dov IZ, Kark JD (2011) 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 26(8):2558–2566PubMedPubMedCentralGoogle Scholar
  10. 10.
    De Miguel E et al (2012) Diagnosis of gout in patients with asymptomatic hyperuricaemia: a pilot ultrasound study. Ann Rheum Dis 71(1):157–158PubMedGoogle Scholar
  11. 11.
    Thiele RG, Schlesinger N (2010) Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved. Rheumatol Int 30:495–503PubMedGoogle Scholar
  12. 12.
    Viggiano D et al (2018) Urate-lowering agents in asymptomatic hyperuricemia: role of urine sediment analysis and musculoskeletal ultrasound. Kidney Blood Press Res 43(2):606–615PubMedGoogle Scholar
  13. 13.
    Badve SV et al (2011) Challenges of conducting a trial of uric-acid-lowering therapy in CKD. Nat Rev Nephrol 7(5):295–300PubMedGoogle Scholar
  14. 14.
    Lee JE et al (2006) Serum uric acid is associated with microalbuminuria in prehypertension. Hypertension 47(5):962–967PubMedGoogle Scholar
  15. 15.
    Tseng CH (2005) Correlation of uric acid and urinary albumin excretion rate in patients with type 2 diabetes mellitus in Taiwan. Kidney Int 68(2):796–801PubMedGoogle Scholar
  16. 16.
    Iseki K et al (2001) Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects. Hypertens Res 24(6):691–697PubMedGoogle Scholar
  17. 17.
    Ryoo JH et al (2013) The association between uric acid and chronic kidney disease in Korean men: a 4-year follow-up study. J Korean Med Sci 28(6):855–860PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kawashima M et al (2011) Association between asymptomatic hyperuricemia and new-onset chronic kidney disease in Japanese male workers: a long-term retrospective cohort study. BMC Nephrol 12:31PubMedPubMedCentralGoogle Scholar
  19. 19.
    Momoki K et al (2017) Hyperuricemia as a predictive marker for progression of nephrosclerosis: clinical assessment of prognostic factors in biopsy-proven arterial/arteriolar nephrosclerosis. J Atheroscler Thromb 24(6):630–642PubMedPubMedCentralGoogle Scholar
  20. 20.
    Wu J et al (2017) Asymptomatic hyperuricemia and coronary artery disease in elderly patients without comorbidities. Oncotarget 8(46):80688–80699PubMedPubMedCentralGoogle Scholar
  21. 21.
    Srivastava A et al (2018) Uric acid and the risks of kidney failure and death in individuals with CKD. Am J Kidney Dis 71(3):362–370PubMedGoogle Scholar
  22. 22.
    Nieradko-Iwanicka B (2018) What is the role of angiotensin receptor blockers in treatment of hyperuricemia coexisting with arterial hypertension? Reumatologia 56(2):106–110PubMedPubMedCentralGoogle Scholar
  23. 23.
    Zhao Y et al (2018) Effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid level: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 20(2):458–462PubMedGoogle Scholar
  24. 24.
    Petreski T et al (2019) Asymptomatic hyperuricemia and cardiovascular mortality in patients with chronic kidney disease who progress to hemodialysis. Int Urol Nephrol 51(6):1013–1018PubMedGoogle Scholar
  25. 25.
    Kim Y et al (2015) Effect of urate lowering therapy on renal disease progression in hyperuricemic patients with chronic kidney disease. J Rheumatol 42(11):2143–2148PubMedGoogle Scholar
  26. 26.
    Siu YP et al (2006) Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis 47(1):51–59Google Scholar
  27. 27.
    Liu P et al (2015) Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study. Clin Endocrinol (Oxf) 83:475–482Google Scholar
  28. 28.
    Sircar D et al (2015) Efficacy of febuxostat for slowing the GFR decline in patients with CKD and asymptomatic hyperuricemia: a 6-month, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis 66:945–950Google Scholar
  29. 29.
    Goicoechea M et al (2015) Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial. Am J Kidney Dis 65(4):543–549PubMedGoogle Scholar
  30. 30.
    Zeng XX et al (2018) Efficacy of febuxostat in hyperuricemic patients with mild-to-moderate chronic kidney disease: a meta-analysis of randomized clinical trials: a PRISMA-compliant article. Medicine (Baltimore) 97(13):e0161Google Scholar
  31. 31.
    Liu X et al (2019) The urate-lowering efficacy and safety of febuxostat versus allopurinol in Chinese patients with asymptomatic hyperuricemia and with chronic kidney disease stages 3-5. Clin Exp Nephrol 23(3):362–370Google Scholar
  32. 32.
    Sarvepalli PS et al (2018) Study of therapeutic efficacy of febuxostat in chronic kidney disease stage IIIA to stage VD. Saudi J Kidney Dis Transpl 29(5):1050–1056Google Scholar
  33. 33.
    Chini LSN, Assis LIS, Lugon JR (2017) Relationship between uric acid levels and risk of chronic kidney disease in a retrospective cohort of Brazilian workers. Braz J Med Biol Res 50(9):e6048PubMedPubMedCentralGoogle Scholar
  34. 34.
    Kim CS et al (2017) Relationship between serum uric acid and mortality among hemodialysis patients: retrospective analysis of Korean end-stage renal disease registry data. Kidney Res Clin Pract 36(4):368–376PubMedPubMedCentralGoogle Scholar
  35. 35.
    Kimura K et al (2018) Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis 72(6):798–810Google Scholar
  36. 36.
    Tanaka K et al (2015) Renoprotective effects of febuxostat in hyperuricemic patients with chronic kidney disease: a parallel-group, randomized, controlled trial. Clin Exp Nephrol 19:1044–1053PubMedGoogle Scholar
  37. 37.
    Kanbay M et al (2011) A randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function. Clin J Am Soc Nephrol 6:1887–1894PubMedPubMedCentralGoogle Scholar
  38. 38.
    Jalal D et al (2017) Vascular function and uric acid-lowering in stage 3 CKD. J Am Soc Nephrol 28(3):943–952PubMedGoogle Scholar
  39. 39.
    Beddhu S et al (2016) A randomized controlled trial of the effects of febuxostat therapy on adipokines and markers of kidney fibrosis in asymptomatic hyperuricemic patients with diabetic nephropathy. Can J Kidney Health Dis 3:2054358116675343PubMedPubMedCentralGoogle Scholar
  40. 40.
    Sanchez-Lozada LG et al (2005) Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 67(1):237–247PubMedGoogle Scholar
  41. 41.
    Kang DH et al (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13(12):2888–2897PubMedGoogle Scholar
  42. 42.
    Corrado A et al (2006) Pathogenesis, clinical findings and management of acute and chronic gout. Minerva Med 97(6):495–509PubMedGoogle Scholar
  43. 43.
    Khanna D et al (2012) 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res 64:1431–1446Google Scholar
  44. 44.
    Vargas-Santos AB, Neogi T (2017) Management of gout and hyperuricemia in CKD. Am J Kidney Dis 70(3):422–439PubMedPubMedCentralGoogle Scholar
  45. 45.
    Stamp L, Dalbeth N (2017) Urate-lowering therapy for asymptomatic hyperuricaemia: a need for caution. Semin Arthritis Rheum 46(4):457–464PubMedGoogle Scholar
  46. 46.
    Yamanaka H (2011) Japanese Society of Gout and Nucleic Acid Metabolism. Japanese guideline for the management of hyperuricemia and gout: second edition. Nucleosides Nucleotides Nucleic Acids 30(12):1018–1029PubMedGoogle Scholar
  47. 47.
    Hakoda M, Kasagi F (2018) Increasing trend of asymptomatic hyperuricemia under treatment with urate-lowering drugs in Japan. Mod Rheumatol 1–5Google Scholar
  48. 48.
    Bellomo G, Selvi A (2018) Uric acid: the lower the better? Contrib Nephrol 192:69–76PubMedGoogle Scholar
  49. 49.
    Ramirez MEG, Bargman JM (2017) Treatment of asymptomatic hyperuricemia in chronic kidney disease: a new target in an old enemy—a review. J Adv Res 8(5):551–554PubMedPubMedCentralGoogle Scholar
  50. 50.
    Eleftheriadis T et al (2017) Asymptomatic hyperuricemia and chronic kidney disease: narrative review of a treatment controversial. J Adv Res 8(5):555–560PubMedPubMedCentralGoogle Scholar
  51. 51.
    Bardin T, Richette P (2017) Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med 15(1):123PubMedPubMedCentralGoogle Scholar
  52. 52.
    Carnovale C, Venegoni M, Clementi E (2014) Allopurinol overuse in asymptomatic hyperuricemia: a teachable moment. JAMA Intern Med 174:1031–1032PubMedGoogle Scholar
  53. 53.
    Gutierrez-Macias A et al (2005) Fatal allopurinol hypersensitivity syndrome after treatment of asymptomatic hyperuricaemia. Br Med J 331:623–624Google Scholar
  54. 54.
    Chamorro A et al (2016) Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 15:869–881PubMedGoogle Scholar
  55. 55.
    Shen C et al (2013) Serum urate and the risk of Parkinson’s disease: results from a meta-analysis. Can J Neurol Sci 40:73–79PubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of NephrologyZhongnan Hospital of Wuhan UniversityWuhanChina

Personalised recommendations