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Proton-pump inhibitors associated with decreased urinary citrate excretion

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Abstract

Introduction

Proton-pump inhibitors (PPIs) may increase the risk of kidney stone formation, but the mechanism has not been elucidated. There is a paucity of literature evaluating the effects of PPIs on urinary metabolites and urine pH.

Methods

We performed a retrospective review of nephrolithiasis patients treated at our institution and compared patients who were taking PPIs to those who were not at the time of their 24-h urine collections. Hierarchical multivariate linear regression was used to evaluate the independent relationship between PPI use and urinary mineral composition.

Results

We identified 301 consecutive patients, 88 (29%) of whom were taking PPIs at the time of their 24-h urine collections. Patients taking PPIs were older and more likely to have medical comorbidities associated with metabolic syndrome such as hypertension, diabetes, and dyslipidemia (p < 0.01). Controlling for these factors, patients taking PPIs were found to have 12% lower 24-h urine citrate excretion (β =  − 0.12, ΔF = 4.24, p = 0.04). There were no other differences in urinary mineral composition between the groups.

Conclusion

Our findings suggest that patients who take PPIs regularly may be at risk for decreased urinary citrate excretion. The consequent decrease in urinary citrate may become clinically significant for patients with other predisposing factors for hypocitraturia.

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References

  1. Scales CD Jr, Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America Project (2012) Prevalence of kidney stones in the United States. Eur Urol 62(1):160–165. https://doi.org/10.1016/j.eururo.2012.03.052

    Article  PubMed  PubMed Central  Google Scholar 

  2. Raheem OA, Khandwala YS, Sur RL, Ghani KR, Denstedt JD (2017) Burden of urolithiasis: trends in prevalence, treatments, and costs. Eur Urol Focus 3(1):18–26. https://doi.org/10.1016/j.euf.2017.04.001

    Article  PubMed  Google Scholar 

  3. Khan SR, Pearle MS, Robertson WG, Gambaro G, Canales BK, Doizi S et al (2017) Kidney stones. Nat Rev Dis Primers. https://doi.org/10.1038/nrdp.2017.1

    Article  PubMed  Google Scholar 

  4. El-Serag HB, Sweet S, Winchester CC, Dent J (2014) Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 63(6):871–880. https://doi.org/10.1136/gutjnl-2012-304269

    Article  PubMed  Google Scholar 

  5. Targownik LE, Metge C, Roos L, Leung S (2007) The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use. Am J Gastroenterol 102(5):942–950. https://doi.org/10.1111/j.1572-0241.2007.01106.x

    Article  PubMed  Google Scholar 

  6. Bai JPF, Hausman E, Lionberger R, Zhang X (2012) Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis. 1. Oral absorption of magnesium. Mol Pharm 9(12):3495–3505. https://doi.org/10.1021/mp300323q

    Article  CAS  PubMed  Google Scholar 

  7. Makunts T, Cohen IV, Awdishu L, Abagyan R (2019) Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis. Sci Rep 9(1):2282. https://doi.org/10.1038/s41598-019-39335-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Simonov M, Abel EE, Skanderson M, Masoud A, Hauser RG, Brandt CA et al (2020) Use of proton pump inhibitors increases risk of incident kidney stones. Clin Gastroenterol Hepatol. https://doi.org/10.1016/j.cgh.2020.02.053

    Article  PubMed  Google Scholar 

  9. Broeren MAC, Geerdink EAM, Vader HL, van den Wall Bake AWL (2009) Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 151(10):755–756. https://doi.org/10.7326/0003-4819-151-10-200911170-00016

    Article  PubMed  Google Scholar 

  10. William JH, Nelson R, Hayman N, Mukamal KJ, Danziger J (2014) Proton-pump inhibitor use is associated with lower urinary magnesium excretion. Nephrology 19(12):798–801. https://doi.org/10.1111/nep.12330

    Article  CAS  PubMed  Google Scholar 

  11. Levin A, Stevens PE, Bilous RW et al (2013) Kidney disease: improving global outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int 3:1–150

    Article  Google Scholar 

  12. Gan KH, Geus WP, Lamers CB, Heijerman HG (1997) Effect of omeprazole 40 mg once daily on intraduodenal and intragastric pH in H. pylori-negative healthy subjects. Dig Dis Sci 42(11):2304–2309. https://doi.org/10.1023/a:1018827003641

    Article  CAS  PubMed  Google Scholar 

  13. Niigaki M, Adachi K, Hirakawa K, Furuta K, Kinoshita Y (2013) Association between metabolic syndrome and prevalence of gastroesophageal reflux disease in a health screening facility in Japan. J Gastroenterol 48(4):463–472. https://doi.org/10.1007/s00535-012-0671-3

    Article  CAS  PubMed  Google Scholar 

  14. Ierardi E, Rosania R, Zotti M, Principe S, Laonigro G, Giorgio F et al (2010) Metabolic syndrome and gastro-esophageal reflux: a link towards a growing interest in developed countries. World J Gastrointest Pathophysiol 1(3):91–96. https://doi.org/10.4291/wjgp.v1.i3.91

    Article  PubMed  PubMed Central  Google Scholar 

  15. Hart E, Dunn TE, Feuerstein S, Jacobs DM (2019) Proton pump inhibitors and risk of acute and chronic kidney disease: a retrospective cohort study. Pharmacotherapy 39(4):443–453. https://doi.org/10.1002/phar.2235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hartman C, Friedlander JI, Moreira DM, Elsamra SE, Smith AD, Okeke Z (2015) Differences in 24-h urine composition between nephrolithiasis patients with and without diabetes mellitus. BJU Int 115(4):619–624. https://doi.org/10.1111/bju.12807

    Article  CAS  PubMed  Google Scholar 

  17. Taylor EN, Curhan GC (2006) Diet and fluid prescription in stone disease. Kidney Int 70(5):835–839. https://doi.org/10.1038/sj.ki.5001656

    Article  CAS  PubMed  Google Scholar 

  18. Zuckerman JM, Assimos DG (2009) Hypocitraturia: pathophysiology and medical management. Rev Urol 11(3):134–144

    PubMed  PubMed Central  Google Scholar 

  19. Keshteli AH, Shaabani P, Tabibian S-R, Saneei P, Esmaillzadeh A, Adibi P (2017) The relationship between fruit and vegetable intake with gastroesophageal reflux disease in Iranian adults. J Res Med Sci 22:125. https://doi.org/10.4103/jrms.JRMS_283_17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Minakuchi H, Yoshida T, Kaburagi N et al (2020) Proton pump inhibitors may hinder hypophosphatemic effect of lanthanum carbonate, but not of ferric citrate hydrate or sucroferric oxyhydroxide, in hemodialysis patients. Ren Fail 42(1):799–806

    Article  CAS  Google Scholar 

  21. Torricelli FC, Reichard C, Monga M (2020) Urolithiasis in complicated inflammatory bowel disease: a comprehensive analysis of urine profile and stone composition. Int Urol Nephrol. https://doi.org/10.1007/s11255-020-02649-x

    Article  PubMed  Google Scholar 

  22. Rudman D, Dedonis JL, Fountain MT, Chandler JB, Gerron GG, Fleming GA et al (1980) Hypocitraturia in patients with gastrointestinal malabsorption. N Engl J Med 303(12):657–661. https://doi.org/10.1056/NEJM198009183031201

    Article  CAS  PubMed  Google Scholar 

  23. Pak CY (1994) Citrate and renal calculi: an update. Miner Electrolyte Metab 20(6):371–377

    CAS  PubMed  Google Scholar 

  24. Shah O, Assimos DG, Holmes RP (2005) Genetic and dietary factors in urinary citrate excretion. J Endourol 19(2):177–182. https://doi.org/10.1089/end.2005.19.177

    Article  PubMed  Google Scholar 

  25. Sakhaee K, Williams RH, Oh MS, Padalino P, Adams-Huet B, Whitson P et al (2009) Alkali absorption and citrate excretion in calcium nephrolithiasis. J Bone Miner Res 8(7):789–794. https://doi.org/10.1002/jbmr.5650080703

    Article  Google Scholar 

  26. Mossetti G, Vuotto P, Rendina D, Numis FG, Viceconti R, Giordano F et al (2003) Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis. J Intern Med 253(2):194–200. https://doi.org/10.1046/j.1365-2796.2003.01086.x

    Article  CAS  PubMed  Google Scholar 

  27. Castle SM, Cooperberg MR, Sadetsky N, Eisner BH, Stoller ML (2010) Adequacy of a single 24-h urine collection for metabolic evaluation of recurrent nephrolithiasis. J Urol 184(2):579–583. https://doi.org/10.1016/j.juro.2010.03.129

    Article  CAS  PubMed  Google Scholar 

  28. Healy KA, Hubosky SG, Bagley DH (2013) 24-h urine collection in the metabolic evaluation of stone formers: Is one study adequate? J Endourol 27(3):374–378. https://doi.org/10.1089/end.2012.0216

    Article  PubMed  Google Scholar 

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Correspondence to Parth M. Patel.

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Patel, P.M., Kandabarow, A.M., Aiwerioghene, E. et al. Proton-pump inhibitors associated with decreased urinary citrate excretion. Int Urol Nephrol 53, 679–683 (2021). https://doi.org/10.1007/s11255-020-02719-0

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  • DOI: https://doi.org/10.1007/s11255-020-02719-0

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