Effect of urate-lowering therapy on the progression of chronic kidney disease in patients with osteoarthritis and asymptomatic hyperuricemia

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Hyperuricemia is an independent risk factor for a wide range of internal organs’ diseases.

The aim: to examine the correlations between asymptomatic hyperuricemia (ASH) and chronic kidney disease (CKD), as well as the effect of drug urate-lowering therapy (ULT) at glomerular filtration rate (GFR) in patients with osteoarthritis (OA).

Material and methods. A retrospective cohort study including data of 1026 OA patients – 530 with BGU and 496 with normal serum uric acid (UA) values was performed. To determine the dynamics of eGFR indicators, its correlation with UA levels in the blood serum and medicamentous ULT, a cohort of patients was selected during a follow-up visit to the research center. A threshold of <360 μmol/L was fixed as target levels (TL) of serum UA. All patients received non-drug therapy aimed at ASH eliminating. Drug ULT was prescribed for persistently elevated UA level in the blood serum despite non-drug treatment, as well as for the presence of cardiovascular risk factors. Xanthine oxidase inhibitors (xOIs) – allopurinol or febuxostat – were used for ASH correction.

Results. In the group of patients with OA having elevated UA levels in the blood serum, arterial hypertension, type 2 diabetes mellitus and obesity were detected significantly more often. Moreover, the presence of ASH was associated with higher levels of glucose, total cholesterol and creatinine in blood serum. Signs of CKD, urolithiasis and chronic pyelonephritis were also significantly more often found in OA patients with ASH. It was fixed, that adjusted odds ratio (OR) for a decrease of eGFR <60 ml/min/1,73 m2 in OA patients while increasing UA level in blood serum per 1 mg/dL should be 1,5 (95% CI: 1,4–1,7). In patients with OA in combination with ASH, who reached the sUA level in the blood serum, regardless of the treatment method, there was a significant increase in eGFR after 3–9, 6–12 and 9–15 months of therapy, while in patients with persistent ASH at the same time intervals, a decrease in eGFR was observed. Moreover, achieving the target value of serum UA led to a significant reduction in the probability of CKD progression after 6–12 months (OR 0,087; 95% CI: 0,011–0,701). In the group of OA patients with ASH who received xOIs, after 6–12 and 9–15 months, a significant increase in eGFR was recorded comparatively with patients receiving non-medicamentous treatment. Along with it, the use of drug ULT significantly reduced the probability of CKD progression after 6–12 (OR 0,252; 95% CI: 0,078–0,815) and 9–15 months (OR 0,216; 95% CI: 0,057–0,822).

Conclusion. According to the data from «Saint Petersburg city register of patients with gout and asymptomatic hyperuricemia», an increase in the level of sUA in the blood serum in patients with OA who do not have signs of gout is associated with a higher prevalence of kidney diseases and the severity of their clinical course. In patients with OA and ASH, getting a CV level of sUA in blood serum, including the same obtained by means of medicamentous ULT, can have a positive effect at eGFR and slow down CKD stage progression. The development of interdisciplinary algorithms for the diagnosis and management of patients with hyperuricemia at the stage of its asymptomatic clinical course is an important strategic task, the solution of which can lead to a reduction of the incidence and intensity of renal pathology progression.

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作者简介

Vadim Mazurov

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

编辑信件的主要联系方式.
Email: maz.nwgmu@yandex.ru
ORCID iD: 0000-0002-0797-2051

MD, professor, academician of RAS, principal scientific advisor, director of the Research Institute of Rheumatology and head of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, head of autoimmune center of Clinical Rheumatology Hospital No. 25, Honored Worker of Science of the Russian Federation

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

Sergey Sayganov

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia

Email: sergey.saiganov@szgmu.ru
ORCID iD: 0000-0001-8325-1937

MD, professor, rector and head of the Department of hospital therapy and cardiology named after M.S. Kushakovsky

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.

Roman Bashkinov

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

Email: bashkinov-roman@mail.ru
ORCID iD: 0000-0001-9344-1304

postgraduate student of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, rheumatologist at Clinical Rheumatology Hospital No. 25

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

Kirill Sapozhnikov

Project office of the North-Western Institute of Management – a branch of Russian Academy of National Economy and Public Administration under the President of the Russian Federation

Email: marinheira@rambler.ru
ORCID iD: 0000-0002-2476-7666

PhD in Medical Sciences, independent expert on research projects of Project office

俄罗斯联邦, 199178, Saint Petersburg, 57/43 Sredny Avenue V.O.

Inna Gaydukova

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

Email: ubp1976@list.ru
ORCID iD: 0000-0003-3500-7256

MD, professor, deputy director of the Research Institute of Rheumatology, professor of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, rheumatologist at Clinical Rheumatology Hospital No. 25

 

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

Daria Tolkacheva

Project office of the North-Western Institute of Management – a branch of Russian Academy of National Economy and Public Administration under the President of the Russian Federation

Email: tolkacheva.d@gmail.com
ORCID iD: 0000-0002-6314-4218

independent expert on research projects of Project office

 

俄罗斯联邦, 199178, Saint Petersburg, 57/43 Sredny Avenue V.O.

Natalia Sableva

Project office of the North-Western Institute of Management – a branch of Russian Academy of National Economy and Public Administration under the President of the Russian Federation

Email: sablevana@gmail.com
ORCID iD: 0000-0002-5809-9221

independent expert on research projects of Project office

俄罗斯联邦, 199178, Saint Petersburg, 57/43 Sredny Avenue V.O.

Oksana Inamova

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

Email: ovig74@mail.ru
ORCID iD: 0000-0001-9126-3639

PhD in Medical Sciences, deputy director of the Research Institute of Rheumatology, assistant at the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, chief physician of Clinical Rheumatology Hospital No. 25

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

Marianna Petrova

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

Email: podagra@bk.ru
ORCID iD: 0000-0001-5261-6614

PhD in Medical Sciences, associate professor of the Department of therapy, rheumatology,
examination of temporary disability and quality of medical care named after E.E. Eichwald, I.I. Mechnikov North-West
State Medical University of the Ministry of Healthcare of Russia, deputy chief physician of Clinical Rheumatology
Hospital No. 25

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

Alexandra Tsinserling

I.I. Mechnikov North-West State Medical University of the Ministry of Healthcare of Russia; Clinical Rheumatology Hospital No. 25

Email: aleksa.fonturenko@mail.ru
ORCID iD: 0000-0003-4860-0518

PhD in Medical Sciences, associate professor of the Department of therapy, rheumatology, examination of temporary disability and quality of medical care named after E.E. Eichwald, deputy chief physician of Clinical Rheumatology Hospital No. 25

俄罗斯联邦, 191014, Saint Petersburg, 41 Kirochnaya Str.; Saint Petersburg

参考

  1. Шальнова С.А., Деев А.Д., Артамонова Г.В. с соавт. Гиперурикемия и ее корреляты в российской популяции (результаты эпидемиологического исследования ЭССЕ-РФ). Рациональная фармакотерапия в кардиологии. 2014; 10(1): 153–159. [Shalnova S.A., Deev A.D., Artamonova G.V. et al. Hyperuricemia and its correlates in the Russian population (results of ESSE-RF epidemiological study). Ratsional’naya farmakoterapiya v kardiologii = Rational Pharmacotherapy in Cardiology. 2014; 10(1): 153–159. https://dx.doi.org/10.20996/1819-6446-2014-10-2-153-159 (In Russ.)]. EDN: SCOUHN.
  2. Chen-Xu M., Yokose C., Rai S.K. 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): 991–99. https://dx.doi.org/10.1002/art.40807.
  3. Мазуров В.И., Башкинов Р.А., Гайдукова И.З., Фонтуренко А.Ю. Влияние бессимптомной гиперурикемии на коморбидные заболевания и возможности ее коррекции. РМЖ. 2021; 29(7): 24–30. [Mazurov V.I., Bashkinov R.A., Gaidukova I.Z., Fonturenko A.Yu. The effect of asymptomatic hyperuricemia on comorbidities and the possibility of its correction. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2021; 29(7): 24–30 (In Russ.)]. EDN: EZWQOO.
  4. Yip K., Cohen R.E., Pillinger M.H. Asymptomatic hyperuricemia: Is it really asymptomatic?. Curr Opin Rheumatol. 2020; 32(1): 71–79. https://dx.doi.org/10.1097/BOR.0000000000000679.
  5. Zhang S., Wang Y., Cheng J. et al. Hyperuricemia and Cardiovascular Disease. Curr Pharm Des. 2019; 25(6): 700–9. https://dx.doi.org/10.2174/138161282566619040812255.
  6. Borghi C., Agabiti-Rosei E., Johnson R.J. et al. Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur J Intern Med. 2020; 80: 1–11. https://dx.doi.org/10.1016/j.ejim.2020.07.006.
  7. 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): 2749–63.
  8. 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): 545–63. https://dx.doi.org/10.5603/CJ.2018.0116.
  9. 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. https://dx.doi.org/10.5603/CJ.a2021.0001.
  10. Чазова И.Е., Жернакова Ю.В., Кисляк О.А. с соавт. Консенсус по ведению пациентов с гиперурикемией и высоким сердечно-сосудистым риском: 2022. Системные гипертензии. 2022; 19(1): 5–22. [Chazova I.E., Zhernakova Yu.V., Kislyak O.A. et al. Consensus on patients with hyperuricemia and high cardiovascular risk treatment: 2022. Sistemnyye gipertenzii = Systemic Hypertension. 2022; 19(1): 5–22 (In Russ.)]. https://dx.doi.org/10.38109/2075-082X-2022-1-5-22. EDN: HBLVVV.
  11. Allen K.D., Thoma L.M., Golightly Y.M. Epidemiology of osteoarthritis. Osteoarthritis Cartilage. 2022; 30(2): 184–95. https://dx.doi.org/10.1016/j.joca.2021.04.020.
  12. Hunter D.J., Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019; 393(10182): 1745–59. https://dx.doi.org/10.1016/S0140-6736(19)30417-9.
  13. Мазуров В.И., Гайдукова И.З., Башкинов Р.А. с соавт. Влияние бессимптомной гиперурикемии на течение коморбидной патологии у пациентов с остеоартритом и возможности ее коррекции. РМЖ. 2021; 29(6): 56–62. [Mazurov V.I., Gaidukova I.Z., Bashkinov R.A. et al. Asymptomatic hyperuricemia impact on the comorbid pathology course in patients with osteoarthritis and the possibility of its correction. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2021; 29(6): 56–62 (In Russ.)]. EDN: GDWNGZ.
  14. Мазуров В.И., Башкинов Р.А., Фонтуренко А.Ю. с соавт. Особенности течения ревматоидного артрита и остеоартрита у пациентов с бессимптомной гиперурикемией. Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. 2020; 12(3): 63–72. [Mazurov V.I., Bashkinov R.A., Fonturenko A.Yu. et al. Features of the course of rheumatoid arthritis and osteoarthritis in patients with asymptomatic hyperuricemia. Herald of North-Western State Medical University named after I.I. Mechnikov. 2020; 12(3): 63–72 (In Russ.)]. https://dx.doi.org/10.17816/mechnikov44234. EDN: XQZWVY.
  15. Neogi T., Krasnokutsky S., Pillinger M.H. Urate and osteoarthritis: Evidence for a reciprocal relationship. Joint Bone Spine. 2019; 86(5): 576–82. https://dx.doi.org/10.1016/j.jbspin.2018.11.002.
  16. Roddy E., Doherty M. Gout and osteoarthritis: A pathogenetic link?. Joint Bone Spine. 2012; 79(5): 425–27. https://dx.doi.org/10.1016/j.jbspin.2012.03.013.
  17. Ding X., Zeng C., Wei J. et al. The associations of serum uric acid level and hyperuricemia with knee osteoarthritis. Rheumatol Int. 2016; 36(4): 567–73. https://dx.doi.org/10.1007/s00296-015-3418-7.
  18. Xiao L., Lin S., Zhan F. The association between serum uric acid level and changes of MRI findings in knee osteoarthritis: A retrospective study (A STROBE-compliant article). Medicine (Baltimore). 2019; 98(21): e15819. https://dx.doi.org/10.1097/MD.0000000000015819.
  19. Sanchez-Lozada L.G. The pathophysiology of uric acid on renal diseases. Contrib Nephrol. 2018; 192: 17–24. https://dx.doi.org/10.1159/000484274.
  20. Tsai C.W., Lin S.Y., Kuo C.C., Huang C.C. Serum uric acid and progression of kidney disease: A longitudinal analysis and mini-review. PLoS One. 2017; 12(1): e0170393. https://dx.doi.org/10.1371/journal.pone.0170393.
  21. Смирнов А.В., Ватазин А.В., Добронравов В.А. с соавт. Клинические рекомендации. Хроническая болезнь почек (ХБП). Нефрология. 2021; 25(5): 10–82. [Smirnov A.V., Vatazin A.V., Dobronravov V.A. Clinical recommendations. Chronic kidney disease (CKD). Nefrologiya = Nephrology (Saint Petersburg). 2021; 25(5): 10–82 (In Russ.)]. https://dx.doi.org/10.36485/1561-6274-2021-25-5-10-84. EDN: GHHTEG.
  22. Nashar K., Fried L.F. 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): 386–91. https://dx.doi.org/10.1053/j.ackd.2012.05.004.
  23. Sharma G., Dubey A., Nolkha N., Singh J.A. Hyperuricemia, urate-lowering therapy, and kidney outcomes: A systematic review and meta-analysis. Ther Adv Musculoskelet Dis. 2021; 13: 1759720X211016661. https://dx.doi.org/10.1177/1759720X211016661.
  24. Bayram D., Tugrul Sezer M., Inal S. et al. The effects of allopurinol on metabolic acidosis and endothelial functions in chronic kidney disease patients. Clin Exp Nephrol. 2015; 19(3): 443–49. https://dx.doi.org/10.1007/s10157-014-1012-z.
  25. Goicoechea M., de Vinuesa S.G., Verdalles U. et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010; 5(8): 1388–93. https://dx.doi.org/10.2215/CJN.01580210.
  26. Mukri M.N.A., Kong W.Y., 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: 563–75. https://dx.doi.org/10.17179/excli2018-1256.
  27. Neogi T., Jansen T.L., Dalbeth N. et al. 2015 gout classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative [published correction appears in Arthritis Rheumatol. 2016; 68(2): 515. Vaquez-Mellado, Janitzia [corrected to Vazquez-Mellado, Janitzia]]. Arthritis Rheumatol. 2015; 67(10): 2557–68. https://dx.doi.org/10.1002/art.39254.
  28. Wallace S.L., Robinson H., Masi A.T. et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977; 20(3): 895–900. https://dx.doi.org/10.1002/art.1780200320.
  29. Levey A.S., Stevens L.A., Schmid C.H. et al. A new equation to estimate glomerular filtration rate [published correction appears in Ann Intern Med. 2011; 155(6): 408]. Ann Intern Med. 2009; 150(9): 604–12. https://dx.doi.org/10.7326/0003-4819-150-9-200905050-00006.
  30. Levey A.S., Stevens L.A. Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions. Am J Kidney Dis. 2010; 55(4): 622–27. https://dx.doi.org/10.1053/j.ajkd.2010.02.337.
  31. Драпкина О.М., Мазуров В.И., Мартынов А.И. с соавт. «В фокусе гиперурикемия». Резолюция Cовета экспертов. Кардиоваскулярная терапия и профилактика. 2023; 22(4): 77–84. [Drapkina O.M., Mazurov V.I., Martynov A.I. et al. «Focus on hyperuricemia». The resolution of the Expert Council. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2023; 22(4): 77–84 (In Russ.)]. https://doi.org/10.15829/1728-8800-2023-3564. EDN: KRCKAU.
  32. Kuwabara M., Niwa K., Hisatome I. et al. Asymptomatic hyperuricemia without comorbidities predicts cardiometabolic diseases: Five-year Japanese cohort study. Hypertension. 2017; 69(6): 1036–44. https://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08998.
  33. Grayson P.C., Kim S.Y., LaValley M., Choi H.K. Hyperuricemia and incident hypertension: A systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2011; 63(1): 102–10. https://dx.doi.org/10.1002/acr.20344.
  34. Wang J., Qin T., Chen J. et al. Hyperuricemia and risk of incident hypertension: A systematic review and meta-analysis of observational studies. PLoS One. 2014; 9(12): e114259. https://dx.doi.org/10.1371/journal.pone.0114259.
  35. Jia Z., Zhang X., Kang S., Wu Y. Serum uric acid levels and incidence of impaired fasting glucose and type 2 diabetes mellitus: A meta-analysis of cohort studies. Diabetes Res Clin Pract. 2013; 101(1): 88–96. https://dx.doi.org/10.1016/j.diabres.2013.03.026.
  36. Lv Q., Meng X.F., He F.F. et al. High serum uric acid and increased risk of type 2 diabetes: A systemic review and meta-analysis of prospective cohort studies. PLoS One. 2013; 8(2): e56864. https://dx.doi.org/10.1371/journal.pone.0056864.
  37. Kodama S., Saito K., Yachi Y. et al. Association between serum uric acid and development of type 2 diabetes. Diabetes Care. 2009; 32(9): 1737–42. https://dx.doi.org/10.2337/dc09-0288.
  38. Yuan H., Yu C., Li X. et al. Serum uric acid levels and risk of metabolic syndrome: A dose-response meta-analysis of prospective studies. J Clin Endocrinol Metab. 2015; 100(11): 4198–207. https://dx.doi.org/10.1210/jc.2015-2527.
  39. Grassi D., Desideri G., Di Giacomantonio A.V. et al. Hyperuricemia and cardiovascular risk. High Blood Press Cardiovasc Prev. 2014; 21(4): 235–42. https://dx.doi.org/10.1007/s40292-014-0046-3.
  40. Perez-Ruiz F., Becker M.A. Inflammation: A possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease. Curr Med Res Opin. 2015; 31 Suppl 2: 9–14. https://dx.doi.org/10.1185/03007995.2015.1087980.
  41. Кобалава Ж.Д., Конради А.О., Недогода С.В. с соавт. Артериальная гипертензия у взрослых. Клинические рекомендации 2020. Российский кардиологический журнал. 2020; 25(3): 149–218. [Kobalava Zh.D., Konradi A.O., Nedogoda S.V. et al. Arterial hypertension in adults. Clinical guidelines 2020. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020; 25(3): 149–218 (In Russ.)]. https://dx.doi.org/10.15829/1560-4071-2020-3-3786. EDN: TCRBRB.
  42. Williams B., Mancia G., Spiering W. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension [published correction appears in Eur Heart J. 2019; 40(5): 475]. Eur Heart J. 2018; 39(33): 3021–104. https://dx.doi.org/10.1093/eurheartj/ehy339.
  43. Чазова И.Е., Жернакова Ю.В., Кисляк О.А. с соавт. Консенсус по ведению пациентов с гиперурикемией и высоким сердечно-сосудистым риском. Системные гипертензии. 2019; 16(4): 8–21. [Chazova I.E., Zhernakova Ju.V., Kisliak O.A. et al. Consensus on patients with hyperuricemia and high cardiovascular risk treatment. Sistemnyye gipertenzii = Systemic Hypertension. 2019; 16(4): 8–21 (In Russ.)]. https://dx.doi.org/10.26442/2075082X.2019.4.190686. EDN: HSKPCZ.
  44. 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. https://dx.doi.org/10.1186/1471-2369-15-122.
  45. 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. https://dx.doi.org/10.1371/journal.pone.0100801.
  46. Li Y.L., 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): 555–61 (In Chinese)].
  47. 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): 1326–41. https://dx.doi.org/10.1016/j.metabol.2016.05.009.
  48. 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. https://dx.doi.org/10.1186/s12882-018-1143-7.
  49. Badve S.V., Pascoe E.M., Tiku A. et al. Effects of allopurinol on the progression of chronic kidney disease. N Engl J Med. 2020; 382(26): 2504–13. https://dx.doi.org/10.1056/NEJMoa1915833.
  50. 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. https://dx.doi.org/10.1053/j.ajkd.2018.06.028.

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