Sulfasalazine related nephrolithiasis in patients with rheumatoid arthritis and ankylosing spondylitis

Abstract

Background Sulfasalazine (SSZ) is an anti-inflammatory and immunomodulatory drug used to treat many inflammatory diseases. Bacteria in the gut metabolize SSZ to active 5-aminosalicylic acid and inactive sulfapyridine. Sulfapyridine can crystallize in the kidney. We aimed to investigate the frequency of nephrolithiasis in patients who were diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and who received SSZ treatment retrospectively. Material and Methods We retrospectively analyzed the files of AS and RA patients in the rheumatology outpatient clinic between 2009 and 2018. We identified patients who underwent kidney ultrasonography at least six months after initiation of SSZ. One hundred six patients and 50 healthy adults were included in the study. Results Only eight patients (6 AS, 2 RA) had nephrolithiasis on ultrasonography, but none in the control group (p=0.046). In logistic regression analysis, no correlation was found between gender, age, vitamin D, parathyroid hormone, and urinary calcium excretion with SSZ use (p>0.05). Conclusion Although, it is noteworthy that these patients are prone to stone formation for various reasons. Therefore, paying attention to the patient’s hydration while using these drugs may prevent such side effects.

Keywords

• nephrolithiasis
• Sulfasalazine
• rheumatoid arthritis
• ankylosing spondylitis

References

1. Azad Khan AK, Piris J, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet. 1977 Oct 29;2(8044):892-5. doi: 10.1016/s0140-6736(77)90831-5.
2. van Riel PL, van Gestel AM, van de Putte LB. Long-term usage and side-effect profile of sulphasalazine in rheumatoid arthritis. Br J Rheumatol. 1995 Nov;34 Suppl 2:40-2.
3. Hopkinson ND, Saiz Garcia F, Gumpel JM. Haematological side-effects of sulphasalazine in inflammatory arthritis. Br J Rheumatol. 1989 Oct;28(5):414-7. doi: 10.1093/rheumatology/28.5.414.
4. Nakajima H, Munakata A, Yoshida Y. Adverse effects of sulfasalazine and treatment of ulcerative colitis with mesalazine. J Gastroenterol. 1995 Nov;30 Suppl 8:115-7.
5. Birketvedt GS, Berg KJ, Fausa O, Florholmen J. Glomerular and tubular renal functions after long-term medication of sulphasalazine, olsalazine, and mesalazine in patients with ulcerative colitis. Inflamm Bowel Dis. 2000 Nov;6(4):275-9. doi: 10.1002/ibd.3780060404.
6. Ransford RA, Langman MJ. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut. 2002 Oct;51(4):536-9. doi: 10.1136/gut.51.4.536.
7. Mustafa S, Alsughayer A, Elgazzar A, Elassar A, Al Sagheer F. Effect of sulfa drugs on kidney function and renal scintigraphy. Nephrology (Carlton). 2014 Apr;19(4):210-6. doi: 10.1111/nep.12200.
8. Rao NP, Preminger GM, Kavanagh JP, eds. Urinary Tract Stone Disease. London: Springer; 2011.

9. Dusseault BN, Croce KJ, Pais VM Jr. Radiographic characteristics of sulfadiazine urolithiasis. Urology. 2009 Apr;73(4):928.e5-6. doi: 10.1016/j.urology.2008.06.035.
10. Fallahi S, Jamshidi AR, Gharibdoost F, Mahmoud MI, Paragomi P, Nicknam MH, Farhadi E, Qorbani M. Urolithiasis in ankylosing spondylitis: Correlation with Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis metrology index (BASMI). Caspian J Intern Med. 2012 Fall;3(4):508-13.
11. Jakobsen AK, Jacobsson LT, Patschan O, Askling J, Kristensen LE. Is nephrolithiasis an unrecognized extra-articular manifestation in ankylosing spondylitis? A prospective population-based Swedish national cohort study with matched general population comparator subjects. PLoS One. 2014 Nov 25;9(11):e113602. doi: 10.1371/journal.pone.0113602.
12. Resorlu M, Gokmen F, Resorlu H, Adam G, Aylanc N, Akbal A, Ozdemir H. Prospective evaluation of the renal morphology and vascular resistance in patients with ankylosing spondylitis. Med Ultrason. 2015 Jun;17(2):180-4. doi: 10.11152/mu.2013.2066.172.dyr.
13. Elian N, Berinde L, Georgescu L, Ocică I, Sabo I. Manifestări nefro-uropatice în spondilita anchilopoietică [Nephro-uropathic manifestations in ankylopoietic spondylitis]. Med Interna (Bucur). 1972 Feb;24(2):187-93 (in Romanian).
14. Korkmaz C, Cansu DÜ, Sayer JA. Urolithiasis as an extraarticular manifestation of ankylosing spondylitis. Rheumatol Int. 2017 Dec;37(12):1949-56. doi: 10.1007/s00296-017-3788-0.
15. El Maghraoui A. Osteoporosis and ankylosing spondylitis. Joint Bone Spine. 2004 Jul;71(4):291-5. doi: 10.1016/j.jbspin.2003.06.002.
16. Ou SM, Chen YT, Shih CJ, Tarng DC. Increased risk of bone fracture among patients with urinary calculi: a nationwide longitudinal population-based study. Osteoporos Int. 2015 Apr;26(4):1261-9. doi: 10.1007/s00198-014-2998-5.
17. Korkmaz C, Ozcan A, Akçar N. Increased frequency of ultrasonographic findings suggestive of renal stones in patients with ankylosing spondylitis. Clin Exp Rheumatol. 2005 May-Jun;23(3):389-92.