Skip to main content

Advertisement

SpringerLink
Log in

Enteric Hyperoxaluria and Kidney Stone Management in Inflammatory Bowel Disease

  • Gastroenterology for Geriatric Patients (A Afzali and S Katz, Section Editors)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of review

Enteric hyperoxaluria is frequently seen in patients with inflammatory bowel disease (IBD). IBD patients are therefore at higher risk of nephrolithiasis, particularly calcium oxalate stones. We reviewed the recent medical literature to elucidate the mechanisms and risk factors behind nephrolithiasis in IBD patients, as well as therapies to treat and prevent the formation of kidney stones.

Recent findings

At present, there are no specific guidelines for screening and monitoring the progression of nephrolithiasis in the IBD population. Yet, recent epidemiologic data suggests that the prevalence of nephrolithiasis in the adult IBD patients is as high as 28%. Enteric oxalate levels of IBD patients are significantly elevated compared with non-IBD patients, and recent studies have shown that the gut microbiota largely mediates this process. In particular, intestinal disruption and malabsorption in IBD patients lead to the decolonization of Oxalobacter formigenes which normally metabolizes oxalate in the gut lumen. As such, future studies are needed to clarify the role of O. formigenes in IBD patients with the goal of devising new therapeutic approaches for nephrolithiasis treatment and risk reduction.

Summary

Enteric hyperoxaluria plays a large role in nephrolithiasis, a serious extra-intestinal manifestation of IBD that may progress to chronic kidney disease. The gut microbiota offers a promising approach to treating and preventing hyperoxaluria in the IBD population.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Date availability

Not applicable.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Sairenji T, Collins KL, Evans DV. An update on inflammatory bowel disease. Prim Care. 2017;44(4):673–92.

    PubMed  Google Scholar 

  2. Bianchi L, Gaiani F, Bizzarri B, Minelli R, Cortegoso Valdivia P, Leandro G, et al. Renal lithiasis and inflammatory bowel diseases, an update on pediatric population. Acta Biomed. 2018;89(9-s):76–80. This is the most current review thus far focusing on kidney stone formation in the pediatric IBD population. It highlights prevalence, risk factors for stone formation, and methods of management which may also be relevant to the adult IBD population.

  3. Gkentzis A, Kimuli M, Cartledge J, Traxer O, Biyani CS. Urolithiasis in inflammatory bowel disease and bariatric surgery. World J Nephrol. 2016;5(6):538–46.

    PubMed  PubMed Central  Google Scholar 

  4. Ziemba JB, Matlaga BR. Epidemiology and economics of nephrolithiasis. Investig Clin Urol. 2017;58(5):299–306.

    PubMed  PubMed Central  Google Scholar 

  5. Scales CD Jr, Smith AC, Hanley JM, Saigal CS. Urologic Diseases in America P. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160–5.

    PubMed  PubMed Central  Google Scholar 

  6. McConnell N, Campbell S, Gillanders I, Rolton H, Danesh B. Risk factors for developing renal stones in inflammatory bowel disease. BJU Int. 2002;89(9):835–41.

    CAS  PubMed  Google Scholar 

  7. Corica D, Romano C. Renal involvement in inflammatory bowel diseases. J Crohns Colitis. 2016;10(2):226–35.

    PubMed  Google Scholar 

  8. Cury DB, Moss AC, Schor N. Nephrolithiasis in patients with inflammatory bowel disease in the community. Int J Nephrol Renov Dis. 2013;6:139–42.

    Google Scholar 

  9. Liu M, Nazzal L. Enteric hyperoxaluria: role of microbiota and antibiotics. Curr Opin Nephrol Hypertens. 2019;28(4):352–9 This review discusses malabsorption in IBD and the relationship between hyperoxaluria and oxalate stone formation. This paper is one of the first to propose gut microbiota as a route of treating nephrolithiasis.

    CAS  PubMed  Google Scholar 

  10. Nazzal L, Puri S, Goldfarb DS. Enteric hyperoxaluria: an important cause of end-stage kidney disease. Nephrol Dial Transplant. 2016;31(3):375–82.

    PubMed  Google Scholar 

  11. Worcester EM. Stones from bowel disease. Endocrinol Metab Clin N Am. 2002;31(4):979–99.

    CAS  Google Scholar 

  12. Hammes MS, Lieske JC, Pawar S, Spargo BH, Toback FG. Calcium oxalate monohydrate crystals stimulate gene expression in renal epithelial cells. Kidney Int. 1995;48(2):501–9.

    CAS  PubMed  Google Scholar 

  13. Jonassen JA, Kohjimoto Y, Scheid CR, Schmidt M. Oxalate toxicity in renal cells. Urol Res. 2005;33(5):329–39.

    CAS  PubMed  Google Scholar 

  14. Mulay SR, Kulkarni OP, Rupanagudi KV, Migliorini A, Darisipudi MN, Vilaysane A, et al. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1beta secretion. J Clin Invest. 2013;123(1):236–46.

    CAS  PubMed  Google Scholar 

  15. Mulay SR, Eberhard JN, Desai J, Marschner JA, Kumar SV, Weidenbusch M, et al. Hyperoxaluria requires TNF receptors to initiate crystal adhesion and kidney stone disease. J Am Soc Nephrol. 2017;28(3):761–8.

    CAS  PubMed  Google Scholar 

  16. Mulay SR, Evan A, Anders HJ. Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease. Nephrol Dial Transplant. 2014;29(3):507–14.

    CAS  PubMed  Google Scholar 

  17. Anders HJ, Suarez-Alvarez B, Grigorescu M, Foresto-Neto O, Steiger S, Desai J, et al. The macrophage phenotype and inflammasome component NLRP3 contributes to nephrocalcinosis-related chronic kidney disease independent from IL-1-mediated tissue injury. Kidney Int. 2018;93(3):656–69.

    CAS  PubMed  Google Scholar 

  18. Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, et al. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 2013;84(5):895–901.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Abratt VR, Reid SJ. Oxalate-degrading bacteria of the human gut as probiotics in the management of kidney stone disease. Adv Appl Microbiol. 2010;72:63–87.

    CAS  PubMed  Google Scholar 

  20. Liu M, Devlin JC, Hu J, Volkova A, Battaglia TW, Byrd A, et al. Microbial contributions to oxalate metabolism in health and disease. medRxiv. 2020:2020.01.27.20018770. This is the first study that brings forth evidence from large-scale multi-omics data to show that in the gut microbiome, O. formigenes dominates oxalate degradation.

  21. Kaufman DW, Kelly JP, Curhan GC, Anderson TE, Dretler SP, Preminger GM, et al. Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones. J Am Soc Nephrol. 2008;19(6):1197–203.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kumar R, Ghoshal UC, Singh G, Mittal RD. Infrequency of colonization with Oxalobacter formigenes in inflammatory bowel disease: possible role in renal stone formation. J Gastroenterol Hepatol. 2004;19(12):1403–9.

    PubMed  Google Scholar 

  23. Viana ML, Pontes RM, Garcia WE, Favero ME, Prete DC, Matsuo T. Crohn’s disease and kidney stones: much more than coincidence? Arq Gastroenterol. 2007;44(3):210–4.

    PubMed  Google Scholar 

  24. Caudarella R, Rizzoli E, Pironi L, Malavolta N, Martelli G, Poggioli G, et al. Renal stone formation in patients with inflammatory bowel disease. Scanning Microsc. 1993;7(1):371–9 discussion 9–80.

    CAS  PubMed  Google Scholar 

  25. Berg W, Gayde S, Uhlemann C, Laube N. Metabolic stress response patterns in urinary compositions of idiopathic calcium oxalate stone formers, patients with chronic bowel diseases and controls. Urol Res. 2010;38(3):161–8.

    CAS  PubMed  Google Scholar 

  26. Trinchieri A, Lizzano R, Castelnuovo C, Zanetti G, Pisani E. Urinary patterns of patients with renal stones associated with chronic inflammatory bowel disease. Arch Ital Urol Androl. 2002;74(2):61–4.

    PubMed  Google Scholar 

  27. Parks JH, Worcester EM, O’Connor RC, Coe FL. Urine stone risk factors in nephrolithiasis patients with and without bowel disease. Kidney Int. 2003;63(1):255–65.

    PubMed  Google Scholar 

  28. Fagagnini S, Heinrich H, Rossel JB, Biedermann L, Frei P, Zeitz J, et al. Risk factors for gallstones and kidney stones in a cohort of patients with inflammatory bowel diseases. PLoS One. 2017;12(10):e0185193.

    PubMed  PubMed Central  Google Scholar 

  29. Ishii G, Nakajima K, Tanaka N, Hara H, Kato M, Ishii N. Clinical evaluation of urolithiasis in Crohn’s disease. Int J Urol. 2009;16(5):477–80.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  31. Muller AF, Stevens PE, McIntyre AS, Ellison H, Logan RF. Experience of 5-aminosalicylate nephrotoxicity in the United Kingdom. Aliment Pharmacol Ther. 2005;21(10):1217–24.

    CAS  PubMed  Google Scholar 

  32. Durando M, Tiu H, Kim JS. Sulfasalazine-induced crystalluria causing severe acute kidney injury. Am J Kidney Dis. 2017;70(6):869–73.

    CAS  PubMed  Google Scholar 

  33. DeMichele J, Rezaizadeh H, Goldstein JI. Sulfasalazine crystalluria-induced anuric renal failure. Clin Gastroenterol Hepatol. 2012;10(2):A32.

    PubMed  Google Scholar 

  34. Zhe M, Hang Z. Nephrolithiasis as a risk factor of chronic kidney disease: a meta-analysis of cohort studies with 4,770,691 participants. Urolithiasis. 2017;45(5):441–8.

    CAS  PubMed  Google Scholar 

  35. Khan SR, Pearle MS, Robertson WG, Gambaro G, Canales BK, Doizi S, et al. Kidney stones. Nat Rev Dis Primers. 2016;2:16008.

    PubMed  PubMed Central  Google Scholar 

  36. Primas C, Novacek G, Schweiger K, Mayer A, Eser A, Papay P, et al. Renal insufficiency in IBD--prevalence and possible pathogenetic aspects. J Crohns Colitis. 2013;7(12):e630–4.

    PubMed  Google Scholar 

  37. Lewis B, Mukewar S, Lopez R, Brzezinski A, Hall P, Shen B. Frequency and risk factors of renal insufficiency in inflammatory bowel disease inpatients. Inflamm Bowel Dis. 2013;19(9):1846–51.

    PubMed  Google Scholar 

  38. Park S, Chun J, Han KD, Soh H, Choi K, Kim JH, et al. Increased end-stage renal disease risk in patients with inflammatory bowel disease: a nationwide population-based study. World J Gastroenterol. 2018;24(42):4798–808.

    PubMed  PubMed Central  Google Scholar 

  39. Varda BK, McNabb-Baltar J, Sood A, Ghani KR, Kibel AS, Letendre J, et al. Urolithiasis and urinary tract infection among patients with inflammatory bowel disease: a review of US emergency department visits between 2006 and 2009. Urology. 2015;85(4):764–70.

    PubMed  Google Scholar 

  40. Gaspar SR, Mendonca T, Oliveira P, Oliveira T, Dias J, Lopes T. Urolithiasis and Crohn’s disease. Urol Ann. 2016;8(3):297–304.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77–84.

    CAS  PubMed  Google Scholar 

  42. Zisman AL. Effectiveness of treatment modalities on kidney stone recurrence. Clin J Am Soc Nephrol. 2017;12(10):1699–708.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Glew RH, Sun Y, Horowitz BL, Konstantinov KN, Barry M, Fair JR, et al. Nephropathy in dietary hyperoxaluria: a potentially preventable acute or chronic kidney disease. World J Nephrol. 2014;3(4):122–42.

    PubMed  PubMed Central  Google Scholar 

  44. D’Alessandro C, Ferraro PM, Cianchi C, Barsotti M, Gambaro G, Cupisti A. Which diet for calcium stone patients: a real-world approach to preventive care. Nutrients. 2019;11(5).

  45. Knauf F, Brewer JR, Flavell RA. Immunity, microbiota and kidney disease. Nat Rev Nephrol. 2019;15(5):263–74.

    PubMed  Google Scholar 

  46. Gul Z, Monga M. Medical and dietary therapy for kidney stone prevention. Korean J Urol. 2014;55(12):775–9.

    PubMed  PubMed Central  Google Scholar 

  47. Tasian GE, Jemielita T, Goldfarb DS, Copelovitch L, Gerber JS, Wu Q, et al. Oral antibiotic exposure and kidney stone disease. J Am Soc Nephrol. 2018;29(6):1731–40.

    PubMed  PubMed Central  Google Scholar 

  48. Lieske JC, Goldfarb DS, De Simone C, Regnier C. Use of a probiotic to decrease enteric hyperoxaluria. Kidney Int. 2005;68(3):1244–9.

    CAS  PubMed  Google Scholar 

  49. Pinheiro VB, Baxmann AC, Tiselius H-G, Heilberg IP. The effect of sodium bicarbonate upon urinary citrate excretion in calcium stone formers. Urology. 2013;82(1):33–7.

    PubMed  Google Scholar 

Download references

Code availability

Not applicable.

Author information

Authors and Affiliations

  1. New York University Langone Health, New York, NY, 10016, USA

    Elissa Lin MD, Joseph Xu MD & Menghan Liu MD

  2. Department of Medicine, New York University Langone Health, New York, NY, 10016, USA

    Lama Nazzal MD & Seymour Katz MD

Authors
  1. Elissa Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Menghan Liu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lama Nazzal MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seymour Katz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Elissa Lin—responsible for entire draft of manuscript.

Joseph Xu—assisted in manuscript writing.

Menghan Liu—designed figure.

Lama Nazzal—manuscript editing.

Seymour Katz—responsible for paper’s concept and manuscript editing.

Corresponding author

Correspondence to Elissa Lin MD.

Ethics declarations

Conflict of interest

Elissa Lin declares that she has no conflict of interest. Joseph Xu declares that he has no conflict of interest. Menghan Liu declares that she has no conflict of interest. Lama Nazzal declares that she has no conflict of interest. Seymour Katz that he has no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Gastroenterology for Geriatric Patients

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, E., Xu, J., Liu, M. et al. Enteric Hyperoxaluria and Kidney Stone Management in Inflammatory Bowel Disease. Curr Treat Options Gastro 18, 384–393 (2020). https://doi.org/10.1007/s11938-020-00295-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-020-00295-x

Keywords

Search

Navigation