Skip to main content

Advertisement

Log in

Urolithiasis as an extraarticular manifestation of ankylosing spondylitis

  • Review on RMDs
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Ankylosing spondylitis (AS) affects sacroiliac and axial joints as well as extraarticular organs, such as the eye, lung, bowel, and heart. Although examples of renal involvement in AS, such as IgA nephropathy, amyloidosis, and glomerulonephritis, have been reported, it has not been emphasized that urolithiasis is frequently formed in the clinical course of AS. Growing evidence indicates that urolithiasis may be observed in AS patients and is more frequent than other extraarticular features. In this review, we will discuss frequency and predictors of AS-related urolithiasis and summarize the possible underlying genetic and biochemical mechanisms. We believe an increased awareness of urolithiasis as a complication of AS will encourage future studies that will shed light on disease mechanisms and preventative therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Van der Heijde D (2008) Ankylosing spondylitis. In: Klippel JH, Stone JH, Crofford LJ, White PH (eds) Primer on the rheumatic disease, 13th edn. Springer, Berlin

    Google Scholar 

  2. Sieper J, Braun J, Rudwaleit M, Boonen A, Zink A (2002) Ankylosing spondylitis: an overview. Ann Rheum Dis 61(Suppl 3):8–18

    Article  Google Scholar 

  3. El Maghraoui A (2011) Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications. Eur J Intern Med 22:554–560

    Article  PubMed  Google Scholar 

  4. Elewaut D, Matucci-Cerinic M (2009) Treatment of ankylosing spondylitis and extra-articular manifestations in everyday rheumatology practice. Rheumatology 48:1029–1035

    Article  CAS  PubMed  Google Scholar 

  5. Korkmaz C, Ozcan A, Akçar N (2005) Increased frequency of ultrasonographic findings suggestive of renal stones in patients with ankylosing spondylitis. Clin Exp Rheumatol 23:389–392

    CAS  PubMed  Google Scholar 

  6. Jakobsen AK, Jacobsson LT, Patschan O, Askling J, Kristensen LE (2014) 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 25:9

    Google Scholar 

  7. Lui NL, Carty A, Haroon N, Shen H, Cook RJ, Inman RD (2011) Clinical correlates of urolithiasis in ankylosing spondylitis. J Rheumatol 38:1953–1956

    Article  PubMed  Google Scholar 

  8. Jakobsen AK, Jacobsson LT, Patschan O, Hopfgarten T, Askling J, Kristensen LE (2015) Surgical interventions for nephrolithiasis in ankylosing spondylitis and the general population. Scand J Urol 21:1–6

    Google Scholar 

  9. Elian N, Berinde L, Georgescu L, Ocica I, Saba I (1972) Nephro-uropathic manifestations in ankylopoietic spondylitis. Med Interna 24:187–193

    CAS  Google Scholar 

  10. Mladenovic V (1973) Nephrolithiasis in ankylosing spondylitis. Rheumatizam 20:106–110

    CAS  Google Scholar 

  11. Jimenez Balderas FJ, Robles EJ, Juan L, Badui E, Arellano H, Espinosa Said L et al (1989) Purine metabolism in ankylosing spondylitis: clinical study. Arch Invest Med 20:163–170

    CAS  Google Scholar 

  12. Incel NA, Gökoğlu F, Nacir B, İncel N (2006) Bone and stone in ankylosing spondylitis: osteoporosis and urolithiasis. Clin Rheumatol 25:667–670

    Article  PubMed  Google Scholar 

  13. Canales BK, Leonard SM, Singh JA, Orzano IM, Zimmermann B, Weiland D et al (2006) Spondyloarthropathy: an independent risk factor for kidney stones. J Endourol 20:542–546

    Article  PubMed  Google Scholar 

  14. Cansu DU, Calışır C, Savaş Yavaş U, Kaşifoğlu T, Korkmaz C (2011) Predictors of radiographic severity and functional disability in Turkish patients with ankylosing spondylitis. Clin Rheumatol 30:557–562

    Article  PubMed  Google Scholar 

  15. Fallahi S, Jamshidi AR, Gharibdoost F, Mahmoudi M, Paragomi P, Nicknam MH et al (2012) Urolithiasis in ankylosing spondylitis: correlation with BASDAI, BASFI and BASMI. Caspian J Intern Med 3:508–513

    PubMed  PubMed Central  Google Scholar 

  16. Resorlu H, Adam G, Aylanc N, Akbal A, Ozdemir H (2015) Prospective evaluation of the renal morphology and vascular resistance inpatients with ankylosing spondylitis. Med Ultrason 17:180–184

    Article  PubMed  Google Scholar 

  17. Moe OW (2006) Kidney Stones: pathophysiology and medical management. Lancet 367(9507):333–344

    Article  CAS  PubMed  Google Scholar 

  18. Sakhaee K, Maalouf NM, Sinnott B (2012) Kiney Stones 2012:pathogenesis, diagnosis, and management. J Clin Endocrinol Metab 97:1847–1860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gaspar SR, Mendonça T, Oliveira P, Oliveira T, Dias J, Lopes T (2016) Urolithiasis and crohn’s disease. Urol Ann 8:297–304

    Article  PubMed  PubMed Central  Google Scholar 

  20. Mielants H, Veys EM, Goemaere S, Goethals K, Cuvelier C, De Vos M (1991) Gut inflammation in the spondyloarthropathies: clinical, radiologic, biologic and genetic features in relation to the type of histology. A prospective study. J Rheumatol 18:1542–1551

    CAS  PubMed  Google Scholar 

  21. Pang SW, Davis JC (2006) Clinical aspects of ankylosing spondylitis. In: Weisman MH, Reveille JD, Van der Heijde D (eds) Ankylosing spondylitis and spondyloarthropathies, 1st edn. Mosby, Philadelphia, pp 145–153

    Google Scholar 

  22. Mielants H, van den Bosch F (2006) Inflammatory bowel disease spondyloarthritis: epidemiology, clinical features, and treatment. In: Weisman MH, Reveille JD, Van der Heijde D (eds) Ankylosing spondylitis and spondyloarthropathies, 1st edn. Mosby, Philadelphia, pp 65–74

    Chapter  Google Scholar 

  23. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP (2008) Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum 58:1020–1025

    Article  CAS  PubMed  Google Scholar 

  25. van Sommeren S, Janse M, Karjalainen J, Fehrmann R, Franke L, Fu J, Weersma RK (2014) Extraintestinal manifestations and complications in inflammatory bowel disease: from sharedgenetics to shared biological pathways. Inflamm Bowel Dis 20:987–994

    PubMed  Google Scholar 

  26. Turina MC, Sieper J, Yeremenko N, Conrad K, Haibel H, Rudwaleit M et al (2014) Calprotectin serum level is an independent marker for radiographic spinal progression in axial spondyloarthritis. Ann Rheum Dis 73:1746–1748

    Article  PubMed  Google Scholar 

  27. Matzkies FG, Targan SR, Berel D, Landers CJ, Reveille JD, McGovern DP et al (2012) Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study. Arthritis Res Ther 14(6):R261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, Roth J (2003) Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut 52:847–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Targan SR, Landers CJ, Yang H, Lodes MJ, Cong Y, Papadakis KA et al (2005) Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease. Gastroenterology 128:2020–2028

    Article  CAS  PubMed  Google Scholar 

  30. Gönüllü E, Bilge NŞ, Cansu DU, Bekmez M, Musmul A, Akçar N et al (2016) Risk factors for urolithiasis in patients with ankylosing spondylitis: a prospective case-control study. Urolithiasis. doi:10.1007/s00240-016-0911-8

    PubMed  Google Scholar 

  31. Shodjai-Moradi E, Ebringer A, Abuljadayel I (1992) IgA antibody response to Klebsiella in ankylosing spondylitis measured by immunoblotting. Ann Rheum Dis 51:233–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Khalafpour S, Ebringer A, Abuljadayel I et al (1988) Antibodies to Klebsiella and Proteus microorganisms in ankylosing spondytitis and rheumatoid arthritis patients measured by ELISA. Br J Rheumatol 27(suppl 2):86–89

    Article  PubMed  Google Scholar 

  33. Yuan GH, Shi GY, Ding YZ (1993) Antibodies to Klebsiella pneumoniae in ankylosing spondylitis. Zhonghua Nei Ka Za Zhi 32:467–469 (in Chinese, English abstract)

    CAS  Google Scholar 

  34. Veys EM, van Laera M (1973) Serum IgG, IgM, and IgA levels in ankylosing spondylitis. Ann Rheum Dis 32:493–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ardiçoğlu O, Atay MB, Ataoğlu H et al (1996) IgA antibodies to Klebsiella in ankylosing spondylitis. Clin Rheumatol 15:573–576

    Article  PubMed  Google Scholar 

  36. Muñoz-Ortego J, Vestergaard P, Rubio JB, Wordsworth P, Judge A, Javaid MK et al (2014) Ankylosing spondylitis is associated with an increased risk of vertebral and nonvertebral clinical fractures: a population-based cohort study. J Bone Miner Res 29:1770–1776

    Article  PubMed  Google Scholar 

  37. Maghraoui AE (2004) Osteoporosis and ankylosing spondylitis. Joint Bone Spine 71:291–295

    Article  PubMed  Google Scholar 

  38. Ou SM, Chen YT, Shih CJ, Tarng DC (2015) Increased risk of bone fracture among patients with urinary calculi: a nationwide longitudinal population-based study. Osteoporos Int 26:1261–1269

    Article  PubMed  Google Scholar 

  39. Klingberg E, Nurkkala M, Carlsten H, Forsblad-d’Elia H (2014) Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis. J Rheumatol 41:1349–1356

    Article  PubMed  Google Scholar 

  40. Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R et al (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262

    Article  PubMed  Google Scholar 

  41. Saad CG, Ribeiro AC, Moraes JC, Takayama L, Goncalves CR, Rodrigues MB, de Oliveira RM, Silva CA, Bonfa E, Pereira RM (2012) Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy? Arthritis Res Ther 14(5):R216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gratacós J, Collado A, Filella X, Sanmartí R, Cañete J, Llena J et al (1994) Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 33:927–931

    Article  PubMed  Google Scholar 

  43. Gratacós J, Collado A, Pons F, Osaba M, Sanmartí R, Roqué M et al (1999) Significant loss of bone mass in patients with early, active ankylosing spondylitis: a followup study. Arthritis Rheum 42:2319–2324

    Article  PubMed  Google Scholar 

  44. Pacifici R (1997) Idiopathic hypercalciuria and osteoporosis—distinct clinical manifestations of increased cytokine induces bone resorption? J Clin Endocrinol Metab 82:29–31

    CAS  PubMed  Google Scholar 

  45. Will R, Bhalla AK, Palmer R, Ring R, Calin A (1989) Osteoporosis in early ankylosing spondylitis: a primary pathological event? Lancet II:1483–1485

    Article  Google Scholar 

  46. Oddsson A, Sulem P, Helgason H, Edvardsson VO, Thorleifsson G, Sveinbjörnsson G et al (2015) Common and rare variants associated with kidney stones and biochemical traits. Nat Commun 14(6):7975

    Article  Google Scholar 

  47. Curhan GC, Willett WC, Rimm EB, Stampfer MJ (1997) Family history and risk of kidney stones. J Am Soc Nephrol 8:1568–1573

    CAS  PubMed  Google Scholar 

  48. Stechman MJ, Loh NY, Thakker RV (2007) Genetics of hypercalciuric nephrolithiasis: renal stone disease. Ann N Y Acad Sci 1116:461–484

    Article  CAS  PubMed  Google Scholar 

  49. Sayer JA (2008) The genetics of nephrolithiasis. Nephron Exp Nephrol 110:e37–e43

    Article  PubMed  Google Scholar 

  50. Tsui FW, Tsui HW, Cheng EY, Stone M, Payne U, Reveille JD et al (2003) Novel genetic markers in the 5′-flanking region of ANKH are associated with ankylosing spondylitis. Arthritis Rheum 48:791–797

    Article  CAS  PubMed  Google Scholar 

  51. Tsui HW, Inman RD, Paterson AD, Reveille JD, Tsui FW (2005) ANKH variants associated with ankylosing spondylitis: gender differences. Arthritis Res Ther 7(3):R513–R525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Liu Z, Cui Y, Zhou X, Zhang X, Han J (2013) Association of mineralization-related genes TNAP and ANKH polymorphisms with ankylosing spondylitis in the Chinese Han population. Biosci Trends 7:89–92

    CAS  PubMed  Google Scholar 

  53. Korkmaz C, Sayer JA (2012) ANKH and renal stone formation in ankylosing spondylitis. J Rheumatol 39:1756

    Article  PubMed  Google Scholar 

  54. Ho AM, Johnson MD, Kingsley DM (2000) Role of the Mouse ank gene in control of tissue calcification and arthritis. Science 289:265–270

    Article  CAS  PubMed  Google Scholar 

  55. Russell RG (1976) Metabolism of inorganic pyrophosphate (PPi). Arthritis Rheum 19(Suppl 3):465–478

    Article  CAS  PubMed  Google Scholar 

  56. Moochhala SH, Sayer JA, Carr G, Simmons NL (2008) Renal calcium stones: insights from the control of bone mineralization. Exp Physiol 93:43–49

    Article  CAS  PubMed  Google Scholar 

  57. Carr G, Sayer JA, Simmons NL (2007) Expression and localisation of the pyrophosphate transporter, ANK, in murine kidney cells. Cell Physiol Biochem 20:507–516

    Article  CAS  PubMed  Google Scholar 

  58. Pimentel-Santos FM, Ligeiro D, Matos M, Mourão AF, Vieira de Sousa E, Pinto P et al (2012) ANKH and susceptibility to and severity of ankylosing spondylitis. J Rheumatol 39(1):131–134

    Article  CAS  PubMed  Google Scholar 

  59. Timms AE, Zhang Y, Bradbury L, Wordsworth BP, Brown MA (2003) Investigation of the role of ANKH in ankylosing spondylitis. Arthritis Rheum 48(10):2898–2902

    Article  CAS  PubMed  Google Scholar 

  60. Hess B (1998) Drug-induced urolithiasis. Curr Opin Urol 8:331–334

    Article  CAS  PubMed  Google Scholar 

  61. De Koninck AS, Groen LA, Maes H, Verstraete AG, Stove V, Delanghe JR (2016) Unusual type of kidney stone. Clin Lab 62:235–239

    Article  PubMed  Google Scholar 

  62. Erturk E, Casemento JB, Guertin KR, Kende AS (1994) Bilateral acetylsulfapyridine nephrolithiasis associated with chronic sulfasalazine therapy. J Urol 151:1605–1606

    Article  CAS  PubMed  Google Scholar 

  63. Yanagisawa R, Kamijo T, Nagase Y (1999) A case of drug induced urolithiasis composed of acetyl sulphapyridine associated with ulcerative colitis. Nihon Hinyokika Gakkai Zasshi 90:462–465 (Japanese)

    CAS  PubMed  Google Scholar 

  64. Russinko PJ, Agarwal S, Choi MJ, Kelty PJ (2003) Obstructive nephropathy secondary to sulfasalazine calculi. Urology 62(4):748

    Article  PubMed  Google Scholar 

  65. Hoffnung JM, Parker MD, Hartz JW (1982) Papillary necrosis mimicking staghorn calculi. Urology 20:325–327

    Article  CAS  PubMed  Google Scholar 

  66. Boonen A, Everens JL (2002) Ankylosing spondylitis: what is the cost to society and can it be reduced? Best Pract Res Clin Rheumatol 16:691–705

    Article  CAS  PubMed  Google Scholar 

  67. Ben-Ami H, Ginesin YI, Behar DM, Fischer D, Edoute Y, Lavy A (2002) Diagnosis and treatment of urinary tract complication in Crohn’s disease: an experience over 15 years. Can J Gastroenterol 16:225–229

    Article  PubMed  Google Scholar 

  68. Sato S, Sasaki I, Naito H, Funayama Y, Fukushima K, Shibata C et al (1999) Management of urinary complications in Crohn’s disease. Surg Today 29:713–717

    Article  CAS  PubMed  Google Scholar 

  69. Boussorra H, Sallami S, Said Y, Chebil M, Najjar T (2013) Evaluation of urinary urolithiasis in Crohn’s disease in Tunisian patients. Tunis Med 91:440–443

    PubMed  Google Scholar 

  70. Keddis MT, Rule AD (2013) Nephrolithiasis and loss of kidney function. Curr Opin Nephrol Hypertens 22:390–396

    Article  PubMed  PubMed Central  Google Scholar 

  71. Vupputuri S, Soucie JM, McClellan W, Sandler DP (2004) History of kidney stones as a possible risk factor for chronic kidney disease. Ann Epidemiol 14:222–228

    Article  PubMed  Google Scholar 

  72. Akman T, Binbay M, Aslan R et al (2012) Long-term outcomes of percutaneous nephrolithotomy in 177 patients with chronic kidney disease: a single center experience. J Urol 187:173–177

    Article  PubMed  Google Scholar 

Download references

Funding

This study was not funded by any company or other society.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cengiz Korkmaz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participant performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Korkmaz, C., Cansu, D.Ü. & Sayer, J.A. Urolithiasis as an extraarticular manifestation of ankylosing spondylitis. Rheumatol Int 37, 1949–1956 (2017). https://doi.org/10.1007/s00296-017-3788-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3788-0

Keywords

Navigation