Impact of urate-lowering therapy on the course of chronic kidney disease in patients with asymptomatic hyperuricemia: a meta-analysis of randomized controlled trials

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The presented study has been carried out to identify the effect of urate-lowering therapy with xanthine oxidase inhibitors on glomerular filtration rate and serum uric acid in patients with asymptomatic hyperuricemia and chronic kidney disease. A systematic review of randomized controlled trials has been conducted; its results based on meta-analysis has been evaluated.

A systematic search and selection of publications in Embase, PubMed, Cochrane Library, and eLibrary databases has been performed. The studied drugs were xanthine oxidase inhibitors: allopurinol and febuxostat. The study considered the following parameters such as efficacy endpoints, namely, glomerular filtration rate and serum uric acid after 3–15 months of follow-up. Clinical and methodological heterogeneity of the included randomized controlled trials has been assessed as well as publication bias and risk of systematic error. Synthesis has been performed using bivariate meta-analysis assessing residual statistical heterogeneity.

7 selected randomized controlled trials (1203 patients) have been included in the meta-analysis. This analysis revealed that medication urate-lowering therapy (allopurinol or febuxostat) was associated with higher glomerular filtration rate (+3.0 ml/min/1.73 m2; 95% confidence interval +0.4 to +5.6; p = 0.022) compared with the controls (placebo/no urate-lowering therapy) at 3–15 months of follow-up. Along with this, medication urate-lowering therapy (allopurinol or febuxostat) has been found to result in lower serum uric acid (−3.3 mg/dl; 95% confidence interval −3.8 to −2.8; р < 0.001) compared to the controls (placebo / no urate-lowering therapy) at 3–15 months of follow-up.

The results of the meta-analysis have demonstrated a positive role of allopurinol and febuxostat in increasing glomerular filtration rate and decreasing serum uric acid in patients with chronic kidney disease and asymptomatic hyperuricemia. The presented data suggest that therapeutic measures aimed at the elimination of asymptomatic hyperuricemia, including the use of xanthine oxidase inhibitors, may be important in slowing the progression of chronic kidney failure and may be additional factors of nephroprotection.

Full Text

Restricted Access

About the authors

Vadim I. Mazurov

North-Western State Medical University named after I.I. Mechnikov; Clinical Rheumatology Hospital No. 25

Email: maz.nwgmu@yandex.ru
ORCID iD: 0000-0002-0797-2051
SPIN-code: 6823-5482
Scopus Author ID: 16936315400

MD, Dr. Sci. (Med.), Professor, Academician of the RAS, Honored Scientist of the Russian Federation

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015; Saint Petersburg

Sergey A. Sayganov

North-Western State Medical University named after I.I. Mechnikov

Email: ssayganov@gmail.com
ORCID iD: 0000-0001-8325-1937
SPIN-code: 2174-6400
Scopus Author ID: 36140532200

MD, Dr. Sci. (Med.), Professor

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015

Anatoly I. Martynov

A.I. Yevdokimov Moscow State University of Medicine and Dentistry

Email: idjema@gmail.com
ORCID iD: 0000-0002-0783-488X
SPIN-code: 5271-3173
Scopus Author ID: 7102769644

MD, Dr. Sci. (Med.), Professor, Academician of the RAS

Russian Federation, Moscow

Roman A. Bashkinov

North-Western State Medical University named after I.I. Mechnikov; Clinical Rheumatology Hospital No. 25

Author for correspondence.
Email: bashkinov-roman@mail.ru
ORCID iD: 0000-0001-9344-1304
SPIN-code: 5169-5066
Scopus Author ID: 57221994610

MD, postgraduate student

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015; Saint Petersburg

Inna Z. Gaydukova

North-Western State Medical University named after I.I. Mechnikov; Clinical Rheumatology Hospital No. 25

Email: ubp1976@list.ru
ORCID iD: 0000-0003-3500-7256
SPIN-code: 3083-7996
Scopus Author ID: 55237525900

MD, Dr. Sci. (Med.), Professor

Russian Federation, 41 Kirochnaya St., Saint Petersburg, 191015; Saint Petersburg

Kirill V. Sapozhnikov

Russian Presidential Academy of National Economy and Public Administration

Email: marinheira@rambler.ru
ORCID iD: 0000-0002-2476-7666
SPIN-code: 2707-0339
Scopus Author ID: 57200810332

MD, Cand. Sci. (Med.)

Russian Federation, Москва

Daria G. Tolkacheva

Russian Presidential Academy of National Economy and Public Administration

Email: tolkacheva.d@gmail.com
ORCID iD: 0000-0002-6314-4218
Scopus Author ID: 57221817074

Independent expert on research projects of Project Office of the North-West Institute of Management - branch office FSBEI HE «Russian Presidential Academy of National Economy and Public Administration»

Russian Federation, Moscow

Natalia A. Sableva

Russian Presidential Academy of National Economy and Public Administration

Email: sablevana@gmail.com
ORCID iD: 0000-0002-5809-9221
Scopus Author ID: 57712944300

Independent expert on research projects of Project Office of the North-West Institute of Management - branch office FSBEI HE «Russian Presidential Academy of National Economy and Public Administration»

Russian Federation, Moscow

Alexandra Yu. Tsinzerling

Clinical Rheumatology Hospital No. 25

Email: aleksa.fonturenko@mail.ru
ORCID iD: 0000-0003-4860-0518
SPIN-code: 5613-9035

Senior laboratory assistant of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, rheumatologist 

Russian Federation, Saint Petersburg

References

  1. Shalnova SA, Deev AD, Artamonova GV, et al. Hyperuricemia and its correlates in the Russian population (results of ESSE-RF epidemiological study). Rational Pharmacotherapy in Cardiology. 2014;10(2):153–159. (In Russ.) doi: 10.20996/1819-6446-2014-10-2-153-159
  2. Chen-Xu M, Yokose C, Rai SK, et al. 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(6):991–999. doi: 10.1002/art.40807
  3. Trifirò G, Morabito P, Cavagna L, et al. Epidemiology of gout and hyperuricaemia in Italy during the years 2005-2009: a nationwide population-based study. Ann Rheum Dis. 2013;72(5):694–700. doi: 10.1136/annrheumdis-2011-201254
  4. Mazurov VI, Bashkinov RA, Gaidukova IZ, Fonturenko AYu. The effect of asymptomatic hyperuricemia on comorbidities and the possibility of its correction. RMJ. 2021;7:24–30. (In Russ.)
  5. Yip K, Cohen RE, Pillinger MH. Asymptomatic hyperuricemia: is it really asymptomatic? Curr Opin Rheumatol. 2020;32(1):71–79. doi: 10.1097/BOR.0000000000000679
  6. Zhang S, Wang Y, Cheng J, et al. Hyperuricemia and cardiovascular disease. Curr Pharm Des. 2019;25(6):700–709. doi: 10.2174/1381612825666190408122557
  7. Borghi C, Agabiti-Rosei E, Johnson RJ, et al. Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 2020;80:1–11. doi: 10.1016/j.ejim.2020.07.006
  8. Wang H, Zhang H, Sun L, Guo W. Roles of hyperuricemia in metabolic syndrome and cardiac-kidney-vascular system diseases. Am J Transl Res. 2018;10(9):2749–2763.
  9. Borghi C, Tykarski A, Widecka K, et al. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk. Cardiol J. 2018;25(5):545–563. doi: 10.5603/CJ.2018.0116
  10. Borghi C, Domienik-Karłowicz J, Tykarski A, et al. Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk: 2021 update. Cardiol J. 2021;28(1):1–14. doi: 10.5603/CJ.a2021.0001
  11. Chazova IE, Zhernakova YuV, Kislyak OA, et al. Consensus on patients with hyperuricemia and high cardiovascular risk treatment: 2022. Systemic Hypertension. 2022;19(1):5–22. (In Russ.) doi: 10.38109/2075-082X-2022-1-5-22
  12. Sánchez-Lozada LG. The Pathophysiology of Uric Acid on Renal Diseases. Contrib Nephrol. 2018;192:17–24. doi: 10.1159/000484274
  13. Kuwabara M, Niwa K, Hisatome I, et al. Asymptomatic hyperuricemia without comorbidities predicts cardiometabolic diseases: Five-Year Japanese Cohort Study. Hypertension. 2017;69(6):1036–1044. doi: 10.1161/HYPERTENSIONAHA.116.08998
  14. Koo BS, Jeong HJ, Son CN, et al. J-shaped relationship between chronic kidney disease and serum uric acid levels: a cross-sectional study on the Korean population. J Rheum Dis. 2021;28(4):225–233. doi: 10.4078/jrd.2021.28.4.225
  15. Tsai CW, Lin SY, Kuo CC, Huang CC. Serum uric acid and progression of kidney disease: a longitudinal analysis and mini-review. PLoS One. 2017;12(1):e0170393. doi: 10.1371/journal.pone.0170393
  16. Li L, Yang C, Zhao Y, et al. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: A systematic review and meta-analysis based on observational cohort studies. BMC Nephrol. 2014;15:122. doi: 10.1186/1471-2369-15-122
  17. Zhu P, Liu Y, Han L, et al. Serum uric acid is associated with incident chronic kidney disease in middle-aged populations: a meta-analysis of 15 cohort studies. PLoS One. 2014;9(6):e100801. doi: 10.1371/journal.pone.0100801
  18. Li YL, Wang L, Li J, et al. The correlation between uric acid and the incidence and prognosis of kidney diseases: a systematic review and meta-analysis of cohort studies. Zhonghua Nei Ke Za Zhi. 2011;50(7):555–561. (In Chinese)
  19. Sharma G, Dubey A, Nolkha N, Singh JA. Hyperuricemia, urate-lowering therapy, and kidney outcomes: a systematic review and meta-analysis. Ther Adv Musculoskelet Dis. 2021;13:1759720X211016661. doi: 10.1177/1759720X211016661
  20. Xia X, Luo Q, Li B, et al. Serum uric acid and mortality in chronic kidney disease: A systematic review and meta-analysis. Metabolism. 2016;65(9):1326–1341. doi: 10.1016/j.metabol.2016.05.009
  21. Luo Q, Xia X, Li B, et al. Serum uric acid and cardiovascular mortality in chronic kidney disease: a meta-analysis. BMC Nephrol. 2019;20(1):18. doi: 10.1186/s12882-018-1143-7
  22. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709–733. doi: 10.1016/S0140-6736(20)30045-3
  23. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives – a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72(3):247–259. doi: 10.1038/sj.ki.5002343
  24. Clinical recommendations. Chronic kidney disease (CKD). Nephrology (Saint-Petersburg). 2021;25(5):10–82. (In Russ.)
  25. Chewcharat A, Chen Y, Thongprayoon C, et al. Febuxostat as a renoprotective agent for treatment of hyperuricaemia: a meta-analysis of randomised controlled trials. Intern Med J. 2021;51(5):752–762. doi: 10.1111/imj.14814
  26. Sampson AL, Singer RF, Walters GD. Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease. Cochrane Database Syst Rev. 2017;10(10):CD009460. doi: 10.1002/14651858.CD009460.pub2
  27. Liu X, Liu K, Sun Q, et al. Efficacy and safety of febuxostat for treating hyperuricemia in patients with chronic kidney disease and in renal transplant recipients: A systematic review and meta-analysis. Exp Ther Med. 2018;16(3):1859–1865. doi: 10.3892/etm.2018.6367
  28. Liu X, Zhai T, Ma R, et al. Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis. Ren Fail. 2018;40(1):289–297. doi: 10.1080/0886022X.2018.1456463
  29. Wang H, Wei Y, Kong X, Xu D. Effects of urate-lowering therapy in hyperuricemia on slowing the progression of renal function: a meta-analysis. J Ren Nutr. 2013;23(5):389–396. doi: 10.1053/j.jrn.2012.08.005
  30. Zhang YF, He F, Ding HH, et al. Effect of uric-acid-lowering therapy on progression of chronic kidney disease: a meta-analysis. J Huazhong Univ Sci Technolog Med Sci. 2014;34(4):476–481. doi: 10.1007/s11596-014-1302-4
  31. Bayram D, Tuğrul Sezer M, İnal S, et al. The effects of allopurinol on metabolic acidosis and endothelial functions in chronic kidney disease patients. Clin Exp Nephrol. 2015;19(3):443–449. doi: 10.1007/s10157-014-1012-z
  32. Goicoechea M, de Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5(8):1388–1393. doi: 10.2215/CJN.01580210
  33. Mukri MNA, Kong WY, Mustafar R, et al. Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial. EXCLI J. 2018;17:563–575. doi: 10.17179/excli2018-1256
  34. Sircar D, Chatterjee S, Waikhom R, et al. 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. 2015;66(6):945–950. doi: 10.1053/j.ajkd.2015.05.017
  35. Shi Y, Chen W, Jalal D, et al. Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial. Kidney Blood Press Res. 2012;35(3):153–160. doi: 10.1159/000331453
  36. Badve SV, Pascoe EM, Tiku A, et al. Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med. 2020;382(26):2504–2513. doi: 10.1056/NEJMoa1915833
  37. Kimura K, Hosoya T, Uchida S, et al. Febuxostat therapy for patients with stage 3 CKD and asymptomatic hyperuricemia: a randomized trial. Am J Kidney Dis. 2018;72(6):798–810. doi: 10.1053/j.ajkd.2018.06.028
  38. Bose B, Badve SV, Hiremath SS, et al. Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2014;29(2):406–413. doi: 10.1093/ndt/gft378
  39. Zhang L, An K, Mou X, et al. Effect of urate-lowering therapy on the progression of kidney function in patients with asymptomatic hyperuricemia: a systematic review and meta-analysis. Front Pharmacol. 2022;12:795082. doi: 10.3389/fphar.2021.795082
  40. Doria A, Galecki AT, Spino C, et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med. 2020;382(26):2493–2503. doi: 10.1056/NEJMoa1916624
  41. Higgins JPT, Thomas J, (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 [Internet]. Cochrane. 2022. Available from: https://training.cochrane.org/handbook/archive/v6.3. Accessed: 07.07.2023.
  42. Nashar K, Fried LF. Hyperuricemia and the progression of chronic kidney disease: is uric acid a marker or an independent risk factor? Adv Chronic Kidney Dis. 2012;19(6):386–391. doi: 10.1053/j.ackd.2012.05.004
  43. Piani F, Johnson RJ. Does gouty nephropathy exist, and is it more common than we think? Kidney Int. 2021;99(1):31–33. doi: 10.1016/j.kint.2020.10.015
  44. Bardin T, Nguyen QD, Tran KM, et al. A cross-sectional study of 502 patients found a diffuse hyperechoic kidney medulla pattern in patients with severe gout. Kidney Int. 2021;99(1):218–226. doi: 10.1016/j.kint.2020.08.024
  45. Kim YJ, Oh SH, Ahn JS, et al. The crucial role of xanthine oxidase in CKD progression associated with hypercholesterolemia. Int J Mol Sci. 2020;21(20):7444. doi: 10.3390/ijms21207444
  46. Sato Y, Feig DI, Stack AG, et al. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol. 2019;15(12):767–775. doi: 10.1038/s41581-019-0174-z
  47. Zeng XX, Tang Y, Hu K, et al. 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). 2018;97(13):e0161. doi: 10.1097/MD.0000000000010161
  48. Lin TC, Hung LY, Chen YC, et al. Effects of febuxostat on renal function in patients with chronic kidney disease: A systematic review and meta-analysis. Medicine (Baltimore). 2019;98(29):e16311. doi: 10.1097/MD.0000000000016311
  49. Zheng Y, Sun J. Febuxostat improves uric acid levels and renal function in patients with chronic kidney disease and hyperuricemia: a meta-analysis. Appl Bionics Biomech. 2022;2022:9704862. doi: 10.1155/2022/9704862
  50. Tien YY, Shih MC, Tien CP, et al. To treat or not to treat? Effect of urate-lowering therapy on renal function, blood pressure and safety in patients with asymptomatic hyperuricemia: a systematic review and network meta-analysis. J Am Board Fam Med. 2022;35(1):140–151. doi: 10.3122/jabfm.2022.01.210273
  51. Sapankaew T, Thadanipon K, Ruenroengbun N, et al. Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials. BMC Nephrol. 2022;23(1):223. doi: 10.1186/s12882-022-02850-3
  52. Kanji T, Gandhi M, Clase CM, Yang R. Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2015;16:58. doi: 10.1186/s12882-015-0047-z
  53. Chazova IE, Zhernakova JuV, Kisliak OA, et al. Consensus on patients with hyperuricemia and high cardiovascular risk treatment. Systemic Hypertension. 2019;16(4):8–21. (In Russ). doi: 10.26442/2075082X.2019.4.190686
  54. Drapkina OM, Mazurov VI, Martynov AI, et al. “Focus on hyperuricemia”. The resolution of the Expert Council. Cardiovascular Therapy and Prevention. 2023;22(4):3564. (In Russ.) doi: 10.15829/1728-8800-2023-3564

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Appendix 1. Systematic search strategies used to perform meta-analyses
Download (39KB)
Indexing metadata
3. Appendix 2. Rates of glomerular filtration rate according to the included studies
Download (61KB)
Indexing metadata
4. Appendix 3. Serum uric acid values from included studies
Download (57KB)
Indexing metadata
5. Appendix 4. Estimation of the risk of systematic error in the analysis of all randomized patient groups (“intent-to-treat”)
Download (43KB)
Indexing metadata
6. Figure. Results of the systematic search and selection of publications to perform the meta-analysis (PRISMA flow diagram)

Download (532KB)
Indexing metadata

Copyright (c) 2024 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 71733 от 08.12.2017.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies