Impairment of renal magnesium transportation in patients with hyperuricemic chronic tubulointerstitial nephritis while using nonsteroidal anti-inflammatory drugs
Abstract. It is generally accepted that the number of patients with gout and chronic hyperuricemic tubulointerstitial nephritis (CHTIN) is steadily increasing; these conditions are often developing sequentially with underlying persistent hyperuricemia. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an indispensable class of drugs for gout, but they have a negative effect at renal function, which, in particular, does not exclude the risk of developing renal magnesium transportation disorders and magnesium-deficient conditions.Voronina N.V., Bulkina V.Yu., Lemeshchenko O.V., Zhmerenetsky K.V.
The aim: to determine the effect of selective NSAIDs (nimesulide, celecoxib, etoricorxib) at renal magnesium transportation in patients with CHTIN.
Materials and methods. The study included 132 patients having HCTIN with serum uric acid level > 360 mmol/l, glomerular filtration rate (GFR) ≥ 60 ml/min./1.73 m2 and chronic gouty arthritis of tophaceous form, who were under dispensary observation by nephrologists and rheumatologists and required NSAIDs due to joint pain syndrome. Using adaptive randomization method, the participants were divided into 3 groups comparable by age, gender, body mass index, nature of joint damage and renal function. Group 1 (n = 48) received nimesulide (course dose 6000 mg/month), group 2 (n = 44) – celecoxib (6000 mg/month), group 3 (n = 40) – etoricoxib (2700 mg/month). Renal magnesium transportation was assessed basing on the estimation of magnesium concentration in blood serum and daily urine with calculation of its clearance and compared with estimated GFR (according to СКD-EPI formula) before the prescription of NSAIDs and on the 30th day of their administration. Routine clinical, laboratory, and ultrasound examination of kidneys allowed us to exclude other somatic pathology.
Results. A 30-day course of treatment with selective cyclooxygenase 2 inhibitors (nimesulide, celecoxib, and etoricoxib) for the treatment of gouty arthritis in HCTIN patients with GFR above 60 ml/min/1.73 m2 significantly reduced estimated GFR, increased urinary magnesium excretion, its renal clearance, and moderately reduced serum magnesium levels. No significant differences were found between studied NSAIDs in their effects on changes in serum magnesium concentration, renal transportation, and eGFR (p >0.05).
Conclusion. The development of magnesium deficiency in the blood, even with short-term administration of NSAIDs, requires compensation for hypomagnesemia and appropriate monitoring.
Keywords
hyperuricemic chronic tubulointerstitial nephritis
nephrotoxicity of nonsteroidal anti-inflammatory drugs
nimesulide
celecoxib
etoricoxib
renal magnesium transportation
References
1. Балкаров И.М., Лебедева М.В., Фомин В.В. Уратная нефропатия. В кн.: Нефрология: национальное руководство. Под ред. Н.А. Мухина. М.: ГЭОТАР-Медиа. 2009; с. 374–384. (Balkarov IM, Lebedeva MV, Fomin VV. Uric nephropathy. In the book: Nephrology: National guidelines. Ed. by Mukhin NA. Moscow: GEOTAR-Media. 2009; pp. 374–384 (In Russ.)).
ISBN: 978-5-9704-1174-2.
2. Johnson RJ, Sanchez Lozada LG, Lanaspa MA, Piani F, Borghi C. Uric acid and chronic kidney disease: Still more to do. Kidney Int Rep. 2022;8(2):229–39.
PMID: 36815099. PMCID: PMC9939362. https://doi.org/10.1016/j.ekir. 2022.11.016
3. Рамеев В.В., Елисеев М.С., Моисеев С.В. Концепция аутовоспаления в генезе подагры и гиперурикемии. Клиническая фармакология и терапия. 2019;28(2):28–33. (Rameev VV, Eliseev MS, Moiseev SV. Autoinflammation in the pathogenesis of gout and hyperuricemia. Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy. 2019;28(2):28–33 (In Russ.)). EDN: GJQJTZ.
4. Xiao J, Zhang XL, Fu C, Han R, Chen W, Lu Y, Ye Z. Soluble uric acid increases NALP3 inflammasome and interleukin-1 expression in human primary renal proximal tubule epithelial cells through the Toll-like receptor 4-mediated pathway. Int J Mol Med. 2015;35(5):1347–54.
PMID: 25813103. https://doi.org/10.3892/ijmm.2015.2148
5. Гаранина Е.Е., Мартынова Е.В., Иванов К.Я., Ризванов А.А., Хайбуллина С.Ф. Инфламмасомы: роль в патогенезе заболеваний и терапевтический потенциал. Ученые записки Казанского университета. Серия: Естественные науки. 2020;162(1):80–111. (Garanina EE, Martynova EV, Ivanov KYa., Rizvanov AA, Khaiboullina SF et al. Inflammasomes: Their role in the pathogenesis of diseases and their therapeutic potential. Uchenye zapiski kazanskogo universiteta. Seriya: Estestvennye nauki = Proceedings of Kazan University. Natural Sciences Series. 2020;162(1):80–111 (In Russ)).
EDN: CFDRQF. https://doi.org/10.26907/2542-064X.2020.1.80-111
6. Кобалава Ж.Д., Конради А.О., Недогода С.В., Шляхто Е.В., Арутюнов Г.П., Баранова Е.И. с соавт. Артериальная гипертензия у взрослых. Клинические рекомендации 2020. Российский кардиологический журнал. 2020;25(3):149–218. (Kobalava ZhD, Konradi AO, Nedogoda, Shlyakhto EV, Arutyunov GP, Baranova EI et al. Arterial hypertension in adults. Clinical guidelines 2020. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2020;25(3):149–218 (In Russ.)).
EDN: TCRBRB. https://doi.org/10.15829/1560-4071-2020-3-3786
7. Драпкина О.М., Концевая А.В., Калинина А.М., Авдеев С.Н., Агальцов М.В., Александрова Л.М. с соавт. Профилактика хронических неинфекционных заболеваний в Российской Федерации. Национальное руководство 2022. Кардиоваскулярная терапия и профилактика. 2022;21(4):5–232. (Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alexandrova LM et al. 2022. Prevention of chronic non-communicable diseases in the Russian Federation. National guidelines. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2022;21(4):5–232 (In Russ)).
EDN: DNBVAT. https://doi.org/10.15829/1728-8800-2022-3235
8. Кобалава Ж.Д., Котовская Ю.В., Толкачева В.В., Мильто А.С. Мочевая кислота – ключевой компонент «кардио-ренометаболического континуума». Кардиоваскулярная терапия и профилактика. 2008;7(4):95–100. (Kobalava ZhD, Kotovskaya YuV, Tolkacheva VV, Milto AS. Uric acid is a key component of the “cardiorenal metabolic continuum”. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2008;7(4):95–100. (In Russ.)).
9. Молчанова О.В., Бритов А.Н., Платонова Е.В. Значение повышенного уровня мочевой кислоты в развитии и профилактике хронических неинфекционных заболеваний. Профилактическая медицина. 2020;23(2):102–108. (Molchanova OV, Britov AN, Platonova EV. The significance of elevated uric acid levels in the development and prevention of chronic non-communicable diseases. Profilakticheskaya meditsina = Preventive Medicine. 2020;23(2):102–108 (In Russ)).
EDN: KJEIBS. https://doi.org/10.17116/profmed202023021102
10. Воронина Н.В. Нефропатия с оксалатно-кальциевой кристаллурией у взрослых: итоги многолетних проспективных исследований. Дальневосточный медицинский журнал. 2018;(1):18–22. (Voronina NV. Nephropathy with oxalate-calcium crystalluria in adults: Results of long-term prospective studies. Dal’nevostochnyy meditsinskiy zhurnal = Far Eastern Medical Journal. 2018;(1):18–22 (In Russ.)). EDN: XMLFQL.
11. Баранова А.В. Прогностическое значение полиморфизма генов вазоактивных систем и концентрация магния при тубулоинтерстициальных поражениях почек у детей школьного возраста. Автореферат диссертации на соискание ученой степени кандидата медицинских наук. Иваново. 2013; 18 с. Доступ: https://medical-diss.com/docreader/357272/a#?page=1 (дата обращения – 07.04.2025). (Baranova AV. The prognostic significance of polymorphism of vasoactive system genes and magnesium concentration in tubulointerstitial lesions of the kidneys in school-aged children. Abstract of the dissertation for the degree of PhD (Medicine). Ivanovo. 2013; 18 pp. URL: https://medical-diss.com/docreader/357272/a#?page=1 (date of access – 07.04.2025) (In Russ.)).
12. Остроумова О.Д., Кочетков А.И., Клепикова М.В. Лекарственно-индуцированный дефицит электролитов. Часть 2. Лекарственно-индуцированная гипомагниемия. РМЖ. 2020;28(12):36–48. (Ostroumova OD, Kochetkov AI, Klepikova MV. Drug-induced electrolyte deficiency. Part 2. Drug-induced hypomagnesemia. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2020;28(12):36–48 (In Russ.)). EDN: FMIZRI.
13. Шилов Е.М., Батюшин М.М. Хронический тубулоинтерстициальный нефрит. В кн.: Нефрология. Клинические рекомендации. Под ред. Е.М. Шилова, А.В. Смирнова, Н.Л. Козловской. М.: ГЭОТАР-Медиа. 2020; с. 490–501. (Shilov EM, Batyushin MM. Chronic tubulointerstitial nephritis. In the book: Nephrology: Clinical guidelines. Ed. by Shilov EM, Smirnov AV, Kozlovskaya N.L. Moscow: GEOTAR-Media. 2020; pp. 490–501 (In Russ.)).
ISBN: 978-5-9704-5570-8.
14. Довгань Е.В. Клиническая фармакология нестероидных противовоспалительных препаратов: курс – на безопасность. РМЖ. 2017;25(13):979–985. (Dovgan EV. Clinical pharmacology of nonsteroidal anti-inflammatory drugs: A focus on safety. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2017;25(13):979–985 (In Russ.)). EDN: ZIHBDF.
15. Zhang X, Donnan PT, Bell S, Guthrie B. Non-steroidal antiinflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: Systematic review and meta-analysis. BMC Nephrol. 2017;18(1):256.
PMID: 28764659. PMCID: PMC5540416. https://doi.org/10.1186/s12882-017-0673-8
16. Чичасова Н.В. Проблема оценки эффективности и безопасности нестероидных противовоспалительных препаратов. Современная ревматология. 2016;10(2):83–88. (Chichasova NV. The problem of assessing the effectiveness and safety of nonsteroidal anti-inflammatory drugs. Sovremennaya revmatologiya = Modern Rheumatology. 2016;10(2):83–88 (In Russ.)). EDN: WXPKLD.
17. Воронина Н.В., Гельмутдинов Д.Д., Лемещенко О.В. Влияние нестероидных противовоспалительных препаратов (диклофенака, целекоксиба, нимесулида, диацереина) на ренальный транспорт мочевой кислоты у больных оксалатной нефропатией с сопутствующим гонартритом. Ульяновский медико-биологический журнал. 2023;(1):27–42. (Voronina NV, Gelmuktidinov DD, Lemeshchenko OV. The influence of non-steroidal anti-inflammatory drugs (diclofenac, celecoxib, nimesulide, diacerein) on renal uric acid transport in patients with oxalate nephropathy accompanied by gonarthrosis. Ul’yanovskiy mediko-biologicheskiy zhurnal = Ulyanovsk Medical and Biological Journal. 2023;(1):27–42 (In Russ.)).
EDN: KUGILN. https://doi.org/10.34014/2227-1848-2023-1-27-42.
18. Cannon C, Curtis S, FitzGerald G, Krum H, Kaur A, Bolognese JA et al.; MEDAL Steering Committee. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: A randomised comparison. Lancet. 2006;368(9549):1771–81.
PMID: 17113426. https://doi.org/10.1016/S0140-6736(06)69666-9.
19. Nissen SE, Yeomans ND, Solomon DH, Luscher TF, Libby P, Husni ME et al. Cardiovascular safety of celecoxib, naproxen, or ibuprofen for arthritis. N Engl J Med. 2016;375(26):2519–29.
PMID: 27959716. https://doi.org/10.1056/NEJMoa1611593
20. Sivera F, Andres M, Carmona L, Kydd AS, Moi J, Seth R et al. Multinational evidence based recommendations for the diagnosis and management of gout: Integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative. Ann Rheum Dis. 2014;73(2):328–35.
PMID: 23868909. PMCID: PMC3913257. https://doi.org/10.1136/annrheumdis-2013-203325
About the Authors
Natalya V. Voronina, MD, Dr. Sci. (Medicine), professor, head of the Department of internal medicine, geriatrics, and instrumental diagnostics, Far Eastern State Medical University of the Ministry of Healthcare of Russia. Address: 680000, Khabarovsk, 35 Muravyova-Amurskogo St.E-mail: mdvoronina@yandex.ru
ORCID: http://orcid.org/0000-0002-3284-8108
Veronika Yu. Bulkina, MD, deputy chief of the medical affairs, Military Clinical Hospital 301 of the Ministry of Defence of the Russian Federation. Address: 680028, 1 Khabarovsk, Serysheva St.
E-mail: rona.76@mail.ru
ORCID: http://orcid.org/0000-0005-0253-3075
Olga V. Lemeshchenko, MD, PhD (Medicine), associate professor of the Department of public health and healthcare organization, dean of the Faculty of residency with the career and employment center, Far Eastern State Medical University of the Ministry of Healthcare of Russia. Address: 680000, Khabarovsk, 35 Muravyova-Amurskogo St.
E-mail: lem_aa@mail.ru
ORCID: http://orcid.org/0000-0002-1051-0958
Konstantin V. Zhmerenetsky, MD, Dr. Sci. (Medicine), associate professor, corresponding member of RAS, rector of the Far Eastern State Medical University of the Ministry of Healthcare of Russia, chief external expert – therapist of the Ministry of Healthcare of Khabarovsk Krai. Address: 680000, Khabarovsk, 35 Muravyova-Amurskogo St.
E-mail: rec@mail.fesmu.ru
ORCID: http://orcid.org/0000-0002-6790-3146
Similar Articles
