Beyond the Joints: Exploring Electrolyte and Renal Complications in Rheumatoid Arthritis
Main Article Content
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily affecting the joints, but its systemic manifestations extend to electrolyte imbalances and renal dysfunction. This review explores the complex interplay between RA, electrolyte disturbances (particularly involving sodium, potassium, calcium, and magnesium), and renal complications. Electrolyte imbalances can exacerbate inflammation and immune dysregulation in RA, either directly or indirectly through renal impairment or pharmacological interventions. Chronic inflammation, hypovolemia, and nephrotoxic effects of medications such as NSAIDs and glucocorticoids contribute to renal dysfunction, including chronic kidney disease (CKD) and, in severe cases, end-stage renal disease (ESRD). While DMARDs and biologics offer therapeutic benefits, they also pose potential risks for renal health. Understanding these interactions is essential for optimizing RA management and minimizing systemic complications.
Article Details
How to Cite
ALKHUDAIR, Dalal.
Beyond the Joints: Exploring Electrolyte and Renal Complications in Rheumatoid Arthritis.
Medical Research Archives, [S.l.], v. 13, n. 6, june 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6657>. Date accessed: 15 july 2025.
doi: https://doi.org/10.18103/mra.v13i6.6657.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Salgado E, Bes-Rastrollo M, de Irala J, Carmona L, Gomez-Reino JJ. High sodium intake is associated with self-reported rheumatoid arthritis: a cross sectional and case control analysis within the SUN cohort. Medicine (Baltimore). 2015;94(37):e924.
3. Sundstrom B, Johansson I, Rantapaa-Dahlqvist S. Interaction between dietary sodium and smoking increases the risk for rheumatoid arthritis: results from a nested case-control study. Rheumatology (Oxford). 2015;54(3): 487–93. https://doi.org/10.1093/rheumatology/keu330.
4. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518–22. https://doi.org/10.103 8/nature11868.
5. Hucke S, Eschborn M, Liebmann M, Herold M, Freise N, Engbers A, Ehling P, Meuth SG, Roth J, Kuhlmann T, Wiendl H, Klotz L. Sodium chloride promotes pro-inflammatory macrophage polarization, thereby aggravating CNS autoimmunity. J Autoimmun. 2016;67:90–101. https://doi.org/10.1016/j. jaut.2015.11.001.
6. Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schroeder A, Neuhofer W, Hilgers K, Manzel A, Schwartz C, Kleinewietfeld M, Voelkl J, Schatz V, Linker RA, Lang F, Voehringer D, Wright MD, Hubner N, Dechend R, Jantsch J, Titze J, Müller DN. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. J Clin Invest. 2015;125(11):4223–38 https://doi.org/10.1172/JCI80919 .
7. Hernandez AL, Kitz A, Wu C, Lowther DE, Rodriguez DM, Vudattu N, Deng S, Herold KC, Kuchroo VK, Kleinewietfeld M, Hafler DA. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. J Clin Invest. 2015;125(11):4212–22. https://doi.org/10.1172/JCI81151 .
8. Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schroeder A, Neuhofer W, et al. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. J Clin Invest.2015; 125: 4223–4238. PMID: 26485286 https://doi.org/10.1172/JCI80919
9. 9.Rastmanesh R, Abargouei AS, Shadman Z, Ebrahimi AA, Weber CE. A pilot study of potassium supplementation in the treatment of hypokalemic patients with rheumatoid arthritis: a randomized, double-blinded, placebo-controlled trial. J Pain. 2008;9(8):722–31. https://doi.org/10.1016/j.jpain.2008. 03.006.
10. Minamino H, Katsushima M, Hashimoto M, et al. Urinary sodium-to-potassium ratio associates with hypertension and current disease activity in patients with rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther 2021;23:96.
11. Jäger E, Murthy S, Schmidt. Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis. Nat Commun. 2020;11(1):4243.
12. Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y. Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 2007;458(1):48–56.
13. Shahi A, Aslani S, Ataollahi M, Mahmoudi M. The role of magnesium in different inflammatory diseases. Inflammopharmacology. 2019;27(4):649–61.
14. Maier JA, Castiglioni S, Locatelli L, Zocchi M, Mazur A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol. 2021;115:37–44.
15. Tejero-Taldo MI, Kramer JH, Mak IuT, Komarov AM, Weglicki WB. The nerve-heart connection in the pro-oxidant response to Mg-deficiency. Heart Fail Rev. 2006;11(1):35–44.
16. Begon S, Pickering G, Eschalier A, Dubray C. Magnesium increases morphine analgesic effect in different experimental models of pain. Anesthesiology. 2002;96(3):627–32.
17. Arablou T, Aryaeian N, Djalali M, Shahram F, Rasouli L. Association between dietary intake of some antioxidant micronutrients with some inflammatory and antioxidant markers in active Rheumatoid Arthritis patients. Int J Vitam Nutr Res. 2019;89(5–6):238–45.
18. Hu C, Zhu F, Liu L, Zhang M, Chen G. Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study. BMJ Open. 2020;10(11): e039640.
19. Libby, P. Inflammation in atherosclerosis. Nature. (2002) 420:868–74. doi: 10.1038/ nature01323
20. Rosenfeld, ME. Inflammation and atherosclerosis: direct versus indirect mechanisms. Curr Opin Pharmacol. (2013) 13:154–60. doi: 10.1016/j.coph.2013.01. 003
21. Suh SH, Jung JH, Oh TR, Yang EM, Choi HS, Kim CS, Bae EH, Ma SK, Han K-D, and Kim SW (2023) Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study. Front. Med.. 10:1116489. doi: 10.3389/fmed.2023. 1116489
22. Castro, LL, Lanna, CCD, Rocha, MP, Ribeiro, ALP, and Telles, RW. Recognition and control of hypertension, diabetes, and dyslipidemia in patients with rheumatoid arthritis. Rheumatol Int. (2018) 38:1437–42. doi: 10.1007/s00296-018-4084-3
23. Sang Heon Suh, Jin Hyung Jung, Tae Ryom Oh, Eun Mi Yang, Hong Sang Choi, Chang Seong Kim, Eun Hui Bae, Seong Kwon Ma, Kyung-Do Han, Soo Wan Kim et al. Rheumatoid arthritis and the risk of end-stage renal disease: A nationwide, population-based study. Frontiers in Medicine. 02 February 2023. DOI 10.3389/fmed.2023.1116489
24. Henrich WL. Nephrotoxicity of non-steroidal anti-inflammatory agents. Am J Kidney Dis 1983;2:478–84.
25. Water balance in rheumatoid arthritis. Rheumatology 2005;44:956. Advance Access publication 29 March 2005. doi:10.1093/rheumatology/keh622.
26. Sterling G. West, MD. Rheumatology secrets. Chapter 81 NSAIDs. 3rd edition.
27. Sterling G. West, MD. Rheumatology secrets. Chapter 82 GCs. 3rd edition.
28. Brillon, D.J.; Zheng, B.; Campbell, R.G.; Matthews, D.E. Effect of cortisol on energy expenditure and amino acid metabolism in humans. Am. J. Physiol. 1995, 268, E501–E513.
29. Sterling G. West, MD. Rheumatology secrets. Chapter 83 MTX. 3rd edition.
30. Sterling G. West, MD. Rheumatology secrets. Chapter 84 cycl /cyc. 3rd edition.
31. Sumida, K, Molnar, MZ, Potukuchi, PK, Hassan, F, Thomas, F, Yamagata, K, et al. Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease. Kidney Int. (2018) 93:1207–16. doi: 10.1016/j.kint.2017.11.025