medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-5-36-42medalphabet-3648Research ArticleСтатьиПобочные эффекты ингибиторов протонной помпы при длительном применении: в фокусе мочевыделительная системаSide effects of proton pump inhibitors with long-term use: focus on the urinary systemhttps://orcid.org/0000-0002-1597-1876ТруханД. И.TrukhanD. I.

Трухан Дмитрий Иванович - д.м.н., доцент, профессор кафедры поликлинической терапии и внутренних болезней.

Омск

Trukhan Dmitry I. - DM Sci (habil.), associate professor, professor at Dept of Polyclinic Therapy and Internal Diseases.

Omsk

dmitry_trukhan@mail.ruhttps://orcid.org/0000-0001-8728-2722ВиктороваИ. А.ViktorovaI. A.

Викторова Инна Анатольевна - д.м.н., профессор, заведующая кафедрой поликлинической терапии и внутренних болезней.

Омск

Viktorova Inna A. - DM Sci (habil.), professor, head of Dept of Polyclinic Therapy and Internal Diseases.

Omsk

vic-inna@mail.ruФГБОУ ВО «Омский государственный медицинский университет» Минздрава РоссииРоссияOmsk State Medical UniversityRussian Federation20240705202405Практическая гастроэнтерология (1)3642Copyright © Трухан Д.И., Викторова И.А., 20242024Трухан Д.И., Викторова И.А.Trukhan D.I., Viktorova I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3648

Ингибиторы протонной помпы (ИПП) являются наиболее эффективными препаратами для лечения кислотозависимых заболеваний. В последние десятилетия использование ИПП растет в геометрической прогрессии. Долгое время ИПП считались полностью безопасными лекарственными веществами как для краткосрочного, так и для длительного применения. Однако, в современных клинических рекомендациях отмечается, что при назначении ИПП в больших дозах на длительный срок следует учитывать возможность развития побочных эффектов. В последние годы опубликован ряд зарубежных обзоров, в которых рассматриваются связи между ИПП и рядом заболеваний/состояний. Проведен поиск в информационных базах PubMed и Scopus публикаций, посвященных безопасности применения ИПП, включавший источники до 30.01.2024. В рамках данного обзора нами рассмотрено влияние длительного применения ИПП на мочевыделительную систему. Приведенный обзор демонстрирует вероятные изменения со стороны мочевыделительной системы и повышенный риск развития нефролитиаза, острого интерстициальногоа нефрит, острого повреждения почек, хронической болезни почек, терминальной почечной недостаточности при длительном применении ИПП, что безусловно следует учитывать при их назначении на длительный срок, особенно у пациентов с коморбидной патологией

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the associations between PPIs and a number of diseases/conditions. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to January 30, 2024. In this review, we examined the effect of long-term use of PPIs on the urinary system. This review demonstrates possible changes in the urinary system and an increased risk of developing nephrolithiasis, acute interstitial nephritis, acute kidney injury, chronic kidney disease, end-stage renal failure with long-term use of PPIs, which should certainly be taken into account when prescribing them for a long period, especially in patients with comorbid pathology.

ингибиторы протонной помпылекарственная безопасностьпобочные эффектыгипомагниемиянефролитиазострый интерстициальный нефритострое повреждение почекхроническая болезнь почектерминальная почечная недостаточностькоморбидностьproton pump inhibitorsdrug safetyside effectshypomagnesemianephrolithiasisacute interstitial nephritisacute kidney injurychronic kidney diseaseend-stage renal failurecomorbidityReferencesТрухан Д. И. Рациональная фармакотерапия в гастроэнтерологии. Справочник поликлинического врача. 2012;10: 18–24. https://elibrary.ru/item.asp?id=22601616Trukhan D. I. Racional`naya farmakoterapiya v gastroe`nterologii. Spravochnik poliklinicheskogo vracha. 2012;10: 18–24. https://elibrary.ru/item.asp?id=22601616 (in Russian).Тарасова Л. В., Трухан Д. И. Лекарственная безопасность в гастроэнтерологии. Экспериментальная и клиническая гастроэнтерология. 2013;4: 81–87. https://elibrary.ru/item.asp?id=21440231Tarasova L. V., Trukhan D. I. Drug safety in gastroenterology. Experimental and clinical gastroenterology. 2013;4: 81–87. https://elibrary.ru/item.asp?id=21440231(in Russian)Трухан Д. И., Коншу Н. В. Рациональная фармакотерапия в клинике внутренних болезней сквозь призму мультиморбидности и лекарственной безопасности. Справочник поликлинического врача. 2019; 2: 10–8. https://www.elibrary.ru/item.asp?id=44162870Trukhan D. I., Konshu N. V. Rational pharmacotherapy in the clinic of internal diseases through the prism of multimorbidity and drug safety. Spravochnik poliklinicheskogo vracha. 2019 2: 10–8 https://www.elibrary.ru/item.asp?id=44162870 (in Russian).Трухан Д. И. Рациональная фармакотерапия в реальной клинической практике сквозь призму мультиморбидности и лекарственной безопасности. Клинический разбор в общей медицине. 2020; 2: 29–39. DOI: 10.47407/kr2020.1.2.00015Trukhan D. I. Rational pharmacotherapy in real clinical practice through the prism of multimorbidity and drug safety. Clinical review for general practice. 2020; 2: 29–39. DOI: 10.47407/kr2020.1.2.00015 (in Russian).Лазебник Л. Б., Ткаченко Е. И., Абдулганиева Д. И., Абдулхаков Р. А., Абдулхаков С. Р., и др. VI Национальные рекомендации по диагностике и лечению кислотозависимых и ассоциированных с Helicobacter pylori заболеваний (VI Московские соглашения). Экспериментальная и клиническая гастроэнтерология. 2017;(2):3–21. https://elibrary.ru/item.asp?id=28870080Lazebnik L. B., Tkachenko E. I., Abdulganiyeva D. I., Abdulkhakov R. A., Abdulkhakov S. R. et al VI National guidelines for the diagnosis and treatment of acid-related and Helicobacter pylori-associated diseases (VI Moscow agreement). Experimental and Clinical Gastroenterology. 2017;(2):3–21. (In Russ.) https://elibrary.ru/item.asp?id=28870080 (in Russian).Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis 2020;75:497–507. DOI: 10.1053/j.ajkd.2019.07.012Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis 2020;75:497–507. DOI: 10.1053/j.ajkd.2019.07.012Novotny M, Klimova B, Valis M. PPI Long Term Use: Risk of Neurological Adverse Events? Front Neurol. 2019 Jan 8;9:1142. doi: 10.3389/fneur.2018.01142.Novotny M, Klimova B, Valis M. PPI Long Term Use: Risk of Neurological Adverse Events? Front Neurol. 2019 Jan 8;9:1142. doi: 10.3389/fneur.2018.01142.Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis 2020;75:497–507. DOI: 10.1053/j.ajkd.2019.07.012Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis 2020;75:497–507. DOI: 10.1053/j.ajkd.2019.07.012Nochaiwong S, Ruengorn C, Awiphan R, Koyratkoson K, Chaisai C, Noppakun K, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant 2018;33:331–342. doi: 10.1093/ndt/gfw470.Nochaiwong S, Ruengorn C, Awiphan R, Koyratkoson K, Chaisai C, Noppakun K, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant 2018;33:331–342. doi: 10.1093/ndt/gfw470.Lu S, Zhao J, Chen X, Xu S, Yang X, Zhang Y, Ma Z, Jiang H, Zhou H. Proton pump inhibitor-induced risk of chronic kidney disease is associated with increase of indoxyl sulfate synthesis via inhibition of CYP2E 1 protein degradation.Chem Biol Interact. 2022 Dec 1;368:110219. doi: 10.1016/j.cbi.2022.110219.Lu S, Zhao J, Chen X, Xu S, Yang X, Zhang Y, Ma Z, Jiang H, Zhou H. Proton pump inhibitor-induced risk of chronic kidney disease is associated with increase of indoxyl sulfate synthesis via inhibition of CYP2E 1 protein degradation.Chem Biol Interact. 2022 Dec 1;368:110219. doi: 10.1016/j.cbi.2022.110219.Makunts T, Cohen IV, Awdishu L, Abagyan R. Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis. Sci Rep 2019;9:2282 doi: 10.1038/s41598–019–39335–7.Makunts T, Cohen IV, Awdishu L, Abagyan R. Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis. Sci Rep 2019;9:2282 doi: 10.1038/s41598–019–39335–7.Gommers LMM, Hoenderop JGJ, de Baaij JHF. Mechanisms of proton pump inhibitor-induced hypomagnesemia. Acta Physiol (Oxf). 2022 Aug;235(4): e13846. doi: 10.1111/apha.13846.Gommers LMM, Hoenderop JGJ, de Baaij JHF. Mechanisms of proton pump inhibitor-induced hypomagnesemia. Acta Physiol (Oxf). 2022 Aug;235(4): e13846. doi: 10.1111/apha.13846.Souza CC, Rigueto LG, Santiago HC, Seguro AC, Girardi AC, Luchi WM. Multiple electrolyte disorders triggered by proton pump inhibitor-induced hypomagnesemia: Case reports with a mini-review of the literature. Clin Nephrol Case Stud. 2024 Jan 4;12:6–11. doi: 10.5414/CNCS111284.Souza CC, Rigueto LG, Santiago HC, Seguro AC, Girardi AC, Luchi WM. Multiple electrolyte disorders triggered by proton pump inhibitor-induced hypomagnesemia: Case reports with a mini-review of the literature. Clin Nephrol Case Stud. 2024 Jan 4;12:6–11. doi: 10.5414/CNCS111284.Luk CP, Parsons R, Lee YP, Hughes JD. Proton pump inhibitor-associated hypomagnesemia: what do FDA data tell us? Ann Pharmacother 2013;47:773–780. doi: 10.1345/aph.1R 556.Luk CP, Parsons R, Lee YP, Hughes JD. Proton pump inhibitor-associated hypomagnesemia: what do FDA data tell us? Ann Pharmacother 2013;47:773–780. doi: 10.1345/aph.1R556.Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PLoS One 2014;9: e112558 doi: 10.1371/journal.pone.0112558Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PLoS One 2014;9: e112558 doi: 10.1371/journal.pone.0112558Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Srivali N, Edmonds PJ, Ungprasert P, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail 2015;37:1237–1241. doi: 10.3109/0886022X.2015.1057800.Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, Srivali N, Edmonds PJ, Ungprasert P, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail 2015;37:1237–1241. doi: 10.3109/0886022X.2015.1057800.Srinutta T, Chewcharat A, Takkavatakarn K, Praditpornsilpa K, Eiam-Ong S, Jaber BL, et al. Proton pump inhibitors and hypomagnesemia: a meta-analysis of observational studies. Medicine (Baltimore) 2019;98: e17788 doi: 10.1097/MD.0000000000017788.Srinutta T, Chewcharat A, Takkavatakarn K, Praditpornsilpa K, Eiam-Ong S, Jaber BL, et al. Proton pump inhibitors and hypomagnesemia: a meta-analysis of observational studies. Medicine (Baltimore) 2019;98: e17788 doi: 10.1097/MD.0000000000017788.Rooney MR, Bell EJ, Alonso A, Pankow JS, Demmer RT, Rudser KD, Chen LY, Lutsey PL. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study.J Clin Gastroenterol. 2021 Sep 1;55(8):677–683. doi: 10.1097/MCG.0000000000001420.Rooney MR, Bell EJ, Alonso A, Pankow JS, Demmer RT, Rudser KD, Chen LY, Lutsey PL. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study.J Clin Gastroenterol. 2021 Sep 1;55(8):677–683. doi: 10.1097/MCG.0000000000001420.Markovits N, Loebstein R, Halkin H, Bialik M, Landes-Westerman J, Lomnicky J, Kurnik D. The association of proton pump inhibitors and hypomagnesemia in the community setting. J Clin Pharmacol. 2014 Aug;54(8):889–95. doi: 10.1002/jcph.316.Markovits N, Loebstein R, Halkin H, Bialik M, Landes-Westerman J, Lomnicky J, Kurnik D. The association of proton pump inhibitors and hypomagnesemia in the community setting. J Clin Pharmacol. 2014 Aug;54(8):889–95. doi: 10.1002/jcph.316.Recart DA, Ferraris A, Petriglieri CI, Alonso Serena M, Bonella MB, Posadas-Martinez ML. Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients. Intern Emerg Med. 2021 Apr;16(3):711–717. doi: 10.1007/s11739–020–02501–1.Recart DA, Ferraris A, Petriglieri CI, Alonso Serena M, Bonella MB, Posadas-Martinez ML. Prevalence and risk factors of long-term proton pump inhibitors-associated hypomagnesemia: a cross-sectional study in hospitalized patients. Intern Emerg Med. 2021 Apr;16(3):711–717. doi: 10.1007/s11739–020–02501–1.Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab. 2009;27(6):635–42. doi: 10.1007/s00774–009–0119-x.Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab. 2009;27(6):635–42. doi: 10.1007/s00774–009–0119-x.Morris C, Pillans P. Proton pump inhibitor-associated hypomagnesaemia and hypocalcaemia. Aust Prescr. 2017 Apr;40(2):79–80. doi: 10.18773/austprescr.2017.019.Morris C, Pillans P. Proton pump inhibitor-associated hypomagnesaemia and hypocalcaemia. Aust Prescr. 2017 Apr;40(2):79–80. doi: 10.18773/austprescr.2017.019.Tagboto S. Severe Electrolyte Disturbances Due to Proton Pump Inhibitor Therapy: An Underrecognized Problem with Potentially Severe Sequelae. Am J Case Rep. 2022 Jul 15;23: e936893. doi: 10.12659/AJCR.936893.Tagboto S. Severe Electrolyte Disturbances Due to Proton Pump Inhibitor Therapy: An Underrecognized Problem with Potentially Severe Sequelae. Am J Case Rep. 2022 Jul 15;23: e936893. doi: 10.12659/AJCR.936893.Al Ali HS, Jabbar AS, Neamah NF, Ibrahim NK Long-Term Use of Omeprazole: Effect on Haematological and Biochemical Parameters..Acta Med Indones. 2022 Oct;54(4):585–594. https://pubmed.ncbi.nlm.nih.gov/36624706/Al Ali HS, Jabbar AS, Neamah NF, Ibrahim NK Long-Term Use of Omeprazole: Effect on Haematological and Biochemical Parameters..Acta Med Indones. 2022 Oct;54(4):585–594. https://pubmed.ncbi.nlm.nih.gov/36624706/Sui W, Miller NL, Gould ER, Zhang KC, Koyama T, Hsi RS. Proton pump inhibitors use and risk of incident nephrolithiasis.Urolithiasis. 2022 Aug;50(4):401–409. doi: 10.1007/s00240–022–01326–1.Sui W, Miller NL, Gould ER, Zhang KC, Koyama T, Hsi RS. Proton pump inhibitors use and risk of incident nephrolithiasis.Urolithiasis. 2022 Aug;50(4):401–409. doi: 10.1007/s00240–022–01326–1.Simonov M, Abel EA, Skanderson M, Masoud A, Hauser RG, Brandt CA, Wilson FP, Laine L. Use of Proton Pump Inhibitors Increases Risk of Incident Kidney Stones.Clin Gastroenterol Hepatol. 2021 Jan;19(1):72–79.e21. doi: 10.1016/j.cgh.2020.02.053.Simonov M, Abel EA, Skanderson M, Masoud A, Hauser RG, Brandt CA, Wilson FP, Laine L. Use of Proton Pump Inhibitors Increases Risk of Incident Kidney Stones.Clin Gastroenterol Hepatol. 2021 Jan;19(1):72–79.e21. doi: 10.1016/j.cgh.2020.02.053.Bapir R, Bhatti KH, Eliwa A, García-Perdomo HA, Gherabi N, Hennessey D, Magri V, Mourmouris P, Ouattara A, Perletti G, Philipraj J, Stamatiou K, Adetola Tolani M, Tzelves L, Trinchieri A, Buchholz N. Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.Arch Ital Urol Androl. 2022 Dec 28;94(4):507–514. doi: 10.4081/aiua.2022.4.507.Bapir R, Bhatti KH, Eliwa A, García-Perdomo HA, Gherabi N, Hennessey D, Magri V, Mourmouris P, Ouattara A, Perletti G, Philipraj J, Stamatiou K, Adetola Tolani M, Tzelves L, Trinchieri A, Buchholz N. Risk of urinary stone formation associated to proton pump inhibitors: A systematic review and metanalysis.Arch Ital Urol Androl. 2022 Dec 28;94(4):507–514. doi: 10.4081/aiua.2022.4.507.Liu W, Wang J, Wang M, Wang M, Liu M. Association of proton pump inhibitor use with risk of kidney stones: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (2007–2018).BMJ Open. 2023 Oct 16;13(10): e075136. doi: 10.1136/bmjopen-2023–075136.Liu W, Wang J, Wang M, Wang M, Liu M. Association of proton pump inhibitor use with risk of kidney stones: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (2007–2018).BMJ Open. 2023 Oct 16;13(10): e075136. doi: 10.1136/bmjopen-2023–075136.Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 2014;86:837–844. doi: 10.1038/ki.2014.74.Blank ML, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 2014;86:837–844. doi: 10.1038/ki.2014.74.Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol Dial Transplant 2004;19:1441–1446. doi: 10.1093/ndt/gfh137.Torpey N, Barker T, Ross C. Drug-induced tubulo-interstitial nephritis secondary to proton pump inhibitors: experience from a single UK renal unit. Nephrol Dial Transplant 2004;19:1441–1446. doi: 10.1093/ndt/gfh137.Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol 2006;4:597–604. doi: 10.1016/j.cgh.2005.11.004.Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol 2006;4:597–604. doi: 10.1016/j.cgh.2005.11.004.Simpson IJ, Marshall MR, Pilmore H, Manley P, Williams L, Thein H, et al. Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases. Nephrology (Carlton) 2006;11:381–385. doi: 10.1111/j.1440–1797.2006.00651.x.Simpson IJ, Marshall MR, Pilmore H, Manley P, Williams L, Thein H, et al. Proton pump inhibitors and acute interstitial nephritis: report and analysis of 15 cases. Nephrology (Carlton) 2006;11:381–385. doi: 10.1111/j.1440–1797.2006.00651.x.Härmark L, van der Wiel HE, de Groot MC, van Grootheest AC. Proton pump inhibitor-induced acute interstitial nephritis. Br J Clin Pharmacol 2007;64:819–823. doi: 10.1111/j.1365–2125.2007.02927.x.Härmark L, van der Wiel HE, de Groot MC, van Grootheest AC. Proton pump inhibitor-induced acute interstitial nephritis. Br J Clin Pharmacol 2007;64:819–823. doi: 10.1111/j.1365–2125.2007.02927.x.Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol 2013;14:150 doi: 10.1186/1471– 2369–14–150.Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol 2013;14:150 doi: 10.1186/1471–2369–14–150.Ikuta K, Nakagawa S, Momo K, Yonezawa A, Itohara K, Sato Y, et al. Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case-control study. BMJ Open 2021;11: e041543 doi: 10.1136/bmjopen-2020–041543.Ikuta K, Nakagawa S, Momo K, Yonezawa A, Itohara K, Sato Y, et al. Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: a nested case-control study. BMJ Open 2021;11: e041543 doi: 10.1136/bmjopen-2020–041543.Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open 2015;3: E 166–E 171. doi: 10.9778/cmajo.20140074.Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open 2015;3: E 166–E 171. doi: 10.9778/cmajo.20140074.Sutton SS, Magagnoli J, Cummings TH, Hardin JW. Risk of acute kidney injury in patients with HIV receiving proton pump inhibitors. J Comp Eff Res 2019;8:781–790. doi: 10.2217/cer-2019–0017.Sutton SS, Magagnoli J, Cummings TH, Hardin JW. Risk of acute kidney injury in patients with HIV receiving proton pump inhibitors. J Comp Eff Res 2019;8:781–790. doi: 10.2217/cer-2019–0017.Svanström H, Lund M, Melbye M, Pasternak B. Use of proton pump inhibitors and the risk of acute kidney injury among patients with rheumatoid arthritis: cohort study. Drug Saf 2018;41:817–826. doi: 10.1007/s40264–018–0663–1.Svanström H, Lund M, Melbye M, Pasternak B. Use of proton pump inhibitors and the risk of acute kidney injury among patients with rheumatoid arthritis: cohort study. Drug Saf 2018;41:817–826. doi: 10.1007/s40264–018–0663–1.Yang Y, George KC, Shang WF, Zeng R, Ge SW, Xu G. Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies. Drug Des Devel Ther 2017;11:1291–1299. doi: 10.2147/DDDT.S130568.Yang Y, George KC, Shang WF, Zeng R, Ge SW, Xu G. Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies. Drug Des Devel Ther 2017;11:1291–1299. doi: 10.2147/DDDT.S130568.Chen G, Ning LJ, Qin Y, Zhao B, Mei D, Li XM. Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data. J Gastroenterol Hepatol. 2021 Jan;36(1):156–162. doi: 10.1111/jgh.15151Chen G, Ning LJ, Qin Y, Zhao B, Mei D, Li XM. Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data. J Gastroenterol Hepatol. 2021 Jan;36(1):156–162. doi: 10.1111/jgh.15151Wu B, Li D, Xu T, Luo M, He Z, Li Y. Proton pump inhibitors associated acute kidney injury and chronic kidney disease: data mining of US FDA adverse event reporting system.Sci Rep. 2021 Feb 11;11(1):3690. doi: 10.1038/s41598–021–83099-y.Wu B, Li D, Xu T, Luo M, He Z, Li Y. Proton pump inhibitors associated acute kidney injury and chronic kidney disease: data mining of US FDA adverse event reporting system.Sci Rep. 2021 Feb 11;11(1):3690. doi: 10.1038/s41598–021–83099-y.Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study.Pharmacotherapy. 2019 Apr;39(4):443–453. doi: 10.1002/phar.2235.Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study.Pharmacotherapy. 2019 Apr;39(4):443–453. doi: 10.1002/phar.2235.Han CT, Islam MM, Poly TN, Lu YC, Lin MC. A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors.J Clin Med. 2023 Mar 24;12(7):2467. doi: 10.3390/jcm12072467.Han CT, Islam MM, Poly TN, Lu YC, Lin MC. A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors.J Clin Med. 2023 Mar 24;12(7):2467. doi: 10.3390/jcm12072467.Arora P, Gupta A, Golzy M, Patel N, Carter RL, Jalal K, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol 2016;17:112 doi: 10.1186/s12882–016–0325–4.Arora P, Gupta A, Golzy M, Patel N, Carter RL, Jalal K, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol 2016;17:112 doi: 10.1186/s12882–016–0325–4.Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 2016;176:238–246. doi: 10.1001/jamainternmed.2015.7193.Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 2016;176:238–246. doi: 10.1001/jamainternmed.2015.7193.Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 2017;91:1482–1494. doi: 10.1016/j.kint.2016.12.021.Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 2017;91:1482–1494. doi: 10.1016/j.kint.2016.12.021.Klatte DCF, Gasparini A, Xu H, de Deco P, Trevisan M, Johansson ALV, et al. Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology 2017;153:702–710. doi: 10.1053/j.gastro.2017.05.046.Klatte DCF, Gasparini A, Xu H, de Deco P, Trevisan M, Johansson ALV, et al. Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology 2017;153:702–710. doi: 10.1053/j.gastro.2017.05.046.Murofushi T, Yagi T, Tsuji D, Furushima D, Fujikura T, Itoh K, Kawakami J. Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan 3. doi: 10.1007/s00210–023–02890-y.Murofushi T, Yagi T, Tsuji D, Furushima D, Fujikura T, Itoh K, Kawakami J. Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study. Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan 3. doi: 10.1007/s00210–023–02890-y.Yang H, Juang SY, Liao KF. Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients. Diabetes Res Clin Pract 2019;147:67–75. doi: 10.1016/j.diabres.2018.11.019.Yang H, Juang SY, Liao KF. Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients. Diabetes Res Clin Pract 2019;147:67–75. doi: 10.1016/j.diabres.2018.11.019.Rodríguez-Poncelas A, Barceló MA, Saez M, Coll-de-Tuero G. Duration and dosing of proton pump inhibitors associated with high incidence of chronic kidney disease in population-based cohort. PLoS One 2018;13: e0204231 doi: 10.1371/journal.pone.0204231.Rodríguez-Poncelas A, Barceló MA, Saez M, Coll-de-Tuero G. Duration and dosing of proton pump inhibitors associated with high incidence of chronic kidney disease in population-based cohort. PLoS One 2018;13: e0204231 doi: 10.1371/journal.pone.0204231.Guedes JVM, Aquino JA, Castro TLB, Augusto de Morais F, Baldoni AO, Belo VS, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One 2020;15: e0229344 doi: 10.1371/journal.pone.0229344.Guedes JVM, Aquino JA, Castro TLB, Augusto de Morais F, Baldoni AO, Belo VS, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One 2020;15: e0229344 doi: 10.1371/journal.pone.0229344.Zhang XY, He QS, Jing Z, He JX, Yuan JQ, Dai XY. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.Front Pharmacol. 2022 Nov 10;13:949699. doi: 10.3389/fphar.2022.949699.Zhang XY, He QS, Jing Z, He JX, Yuan JQ, Dai XY. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank.Front Pharmacol. 2022 Nov 10;13:949699. doi: 10.3389/fphar.2022.949699.Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies.J Clin Med. 2023 Mar 15;12(6):2262. doi: 10.3390/jcm12062262.Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies.J Clin Med. 2023 Mar 15;12(6):2262. doi: 10.3390/jcm12062262.Wijarnpreecha K, Thongprayoon C, Chesdachai S, Panjawatanana P, Ungprasert P, Cheungpasitporn W. Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis.Dig Dis Sci. 2017 Oct;62(10):2821–2827. doi: 10.1007/s10620–017–4725–5.Wijarnpreecha K, Thongprayoon C, Chesdachai S, Panjawatanana P, Ungprasert P, Cheungpasitporn W. Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis.Dig Dis Sci. 2017 Oct;62(10):2821–2827. doi: 10.1007/s10620–017–4725–5.Peng YC, Lin CL, Yeh HZ, Chang CS, Wu YL, Kao CH. Association between the use of proton pump inhibitors and the risk of ESRD in renal diseases: a population-based, case-control study. Medicine (Baltimore) 2016;95: e3363 doi: 10.1097/MD.0000000000003363.Peng YC, Lin CL, Yeh HZ, Chang CS, Wu YL, Kao CH. Association between the use of proton pump inhibitors and the risk of ESRD in renal diseases: a population-based, case-control study. Medicine (Baltimore) 2016;95: e3363 doi: 10.1097/MD.0000000000003363.Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol 2016;27:3153–3163. doi: 10.1681/ASN.2015121377.Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol 2016;27:3153–3163. doi: 10.1681/ASN.2015121377.Haastrup PF, Jarbøl DE, Thompson W, Hansen JM, Søndergaard J, Rasmussen S. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol 2021;8: e000563 doi: 10.1136/bmjgast-2020–000563.Haastrup PF, Jarbøl DE, Thompson W, Hansen JM, Søndergaard J, Rasmussen S. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol 2021;8: e000563 doi: 10.1136/bmjgast-2020–000563.Tawam D, Baladi M, Jungsuwadee P, Earl G, Han J. The Positive Association between Proton Pump Inhibitors and Clostridium Difficile Infection.Innov Pharm. 2021 Mar 9;12(1):10.24926/iip.v12i1.3439. doi: 10.24926/iip.v12i1.3439.Tawam D, Baladi M, Jungsuwadee P, Earl G, Han J. The Positive Association between Proton Pump Inhibitors and Clostridium Difficile Infection.Innov Pharm. 2021 Mar 9;12(1):10.24926/iip.v12i1.3439. doi: 10.24926/iip.v12i1.3439.Marcum ZA, Vande Griend JP, Linnebur SA. FDA drug safety communications: a narrative review and clinical considerations for older adults. Am J Geriatr Pharmacother. 2012 Aug;10(4):264–71. doi: 10.1016/j.amjopharm.2012.05.002.Marcum ZA, Vande Griend JP, Linnebur SA. FDA drug safety communications: a narrative review and clinical considerations for older adults. Am J Geriatr Pharmacother. 2012 Aug;10(4):264–71. doi: 10.1016/j.amjopharm.2012.05.002.Lespessailles E, Toumi H. Proton Pump Inhibitors and Bone Health: An Update Narrative Review. Int J Mol Sci. 2022 Sep 14;23(18):10733. doi: 10.3390/ijms231810733.Lespessailles E, Toumi H. Proton Pump Inhibitors and Bone Health: An Update Narrative Review. Int J Mol Sci. 2022 Sep 14;23(18):10733. doi: 10.3390/ijms231810733.Zhang ML, Fan YX, Meng R, Cai WK, Yin SJ, Zhou T, et al. Proton pump inhibitors and cancer risk: an umbrella review and meta-analysis of observational studies. Am J Clin Oncol 2022;45:475–485. doi: 10.1097/COC.0000000000000949.Zhang ML, Fan YX, Meng R, Cai WK, Yin SJ, Zhou T, et al. Proton pump inhibitors and cancer risk: an umbrella review and meta-analysis of observational studies. Am J Clin Oncol 2022;45:475–485. doi: 10.1097/COC.0000000000000949.Sun S, Cui Z, Zhou M, Li R, Li H, Zhang S, et al. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil 2017;29: e12926 doi: 10.1111/nmo.12926.Sun S, Cui Z, Zhou M, Li R, Li H, Zhang S, et al. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil 2017;29: e12926 doi: 10.1111/nmo.12926.Sehested TSG, Gerds TA, Fosbøl EL, Hansen PW, Charlot MG, Carlson N, et al. Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction. J Intern Med 2018;283:268–281. doi: 10.1111/joim.12698Sehested TSG, Gerds TA, Fosbøl EL, Hansen PW, Charlot MG, Carlson N, et al. Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction. J Intern Med 2018;283:268–281. doi: 10.1111/joim.12698Li ZH, Zhong WF, Qiu CS, Yang P, Song WQ, Shen D, Zhang XR, Liu D, Chen YJ, Chen PL, Huang QM, Chen Q, Wang XM, Chung VCH, Gao X, Kraus VB, Liu SD, Mao C. Association between regular proton pump inhibitors use and cardiovascular outcomes: A large prospective cohort study.Int J Cardiol. 2024 Jan 15;395:131567. doi: 10.1016/j.ijcard.2023.131567.Li ZH, Zhong WF, Qiu CS, Yang P, Song WQ, Shen D, Zhang XR, Liu D, Chen YJ, Chen PL, Huang QM, Chen Q, Wang XM, Chung VCH, Gao X, Kraus VB, Liu SD, Mao C. Association between regular proton pump inhibitors use and cardiovascular outcomes: A large prospective cohort study.Int J Cardiol. 2024 Jan 15;395:131567. doi: 10.1016/j.ijcard.2023.131567.Yuan J., He O., Nguyen LH. et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020 Sep 28; gutjnl-2020–322557. doi: 10.1136/gutjnl-2020–322557.Yuan J., He O., Nguyen LH. et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut. 2020 Sep 28; gutjnl-2020–322557. doi: 10.1136/gutjnl-2020–322557.Ciardullo S, Rea F, Savaré L, Morabito G, Perseghin G, Corrao G. Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study.J Clin Endocrinol Metab. 2022 Jun 16;107(7): e2671-e2679. doi: 10.1210/clinem/dgac231.Ciardullo S, Rea F, Savaré L, Morabito G, Perseghin G, Corrao G. Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study.J Clin Endocrinol Metab. 2022 Jun 16;107(7): e2671-e2679. doi: 10.1210/clinem/dgac231.Czarniak P, Ahmadizar F, Hughes J, Parsons R, Kavousi M, Ikram M, Stricker BH. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study.Br J Clin Pharmacol. 2022 Jun;88(6):2718–2726. doi: 10.1111/bcp.15182Czarniak P, Ahmadizar F, Hughes J, Parsons R, Kavousi M, Ikram M, Stricker BH. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study.Br J Clin Pharmacol. 2022 Jun;88(6):2718–2726. doi: 10.1111/bcp.15182Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis.World J Diabetes. 2023 Feb 15;14(2):120–129. doi: 10.4239/wjd.v14.i2.120.Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis.World J Diabetes. 2023 Feb 15;14(2):120–129. doi: 10.4239/wjd.v14.i2.120.Chenchula S, Sharma P, Ghanta MK, Amerneni KC, Rajakarunakaran P, Saggurthi P, Chandra MB, Gupta R, Chavan M. Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis. Curr Diabetes Rev. 2024 Jan 12. doi: 10.2174/0115733998254869231101095222.Chenchula S, Sharma P, Ghanta MK, Amerneni KC, Rajakarunakaran P, Saggurthi P, Chandra MB, Gupta R, Chavan M. Association and Mechanisms of Proton Pump Inhibitors Use with Type-2 Diabetes Mellitus Incidence in Adults: A Systemic Review and Metaanalysis. Curr Diabetes Rev. 2024 Jan 12. doi: 10.2174/0115733998254869231101095222.Salvo EM, Ferko NC, Cash SB, Gonzalez A, Kahrilas PJ. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther. 2021 Jul;54(2):129–143. doi: 10.1111/apt.16407.Salvo EM, Ferko NC, Cash SB, Gonzalez A, Kahrilas PJ. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther. 2021 Jul;54(2):129–143. doi: 10.1111/apt.16407.Chinzon D, Domingues G, Tosetto N, Perrotti M. Safety of long-term proton pump inhibitors: facts and myths. Arq Gastroenterol. 2022 Apr-Jun;59(2):219–225. doi: 10.1590/S0004–2803.202202000–40Chinzon D, Domingues G, Tosetto N, Perrotti M. Safety of long-term proton pump inhibitors: facts and myths. Arq Gastroenterol. 2022 Apr-Jun;59(2):219–225. doi: 10.1590/S0004–2803.202202000–40Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J. 2023 May;59(2):115–127. doi: 10.4068/cmj.2023.59.2.115.Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J. 2023 May;59(2):115–127. doi: 10.4068/cmj.2023.59.2.115.Parmar MP, Kaleem S, Samuganathan P, Ishfaq L, Anne T, Patel Y, Bollu S, Vempati R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review.Cureus. 2023 Dec 3;15(12): e49883. doi: 10.7759/cureus.49883.Parmar MP, Kaleem S, Samuganathan P, Ishfaq L, Anne T, Patel Y, Bollu S, Vempati R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review.Cureus. 2023 Dec 3;15(12): e49883. doi: 10.7759/cureus.49883.Saad SY, Najjar TA, Al-Sohaibani MO. The effect of rebamipide on cisplatin-induced nephrotoxicity in rats. Pharmacol Res. 2000 Jul;42(1):81–6. doi: 10.1006/phrs.2000.0662.Saad SY, Najjar TA, Al-Sohaibani MO. The effect of rebamipide on cisplatin-induced nephrotoxicity in rats. Pharmacol Res. 2000 Jul;42(1):81–6. doi: 10.1006/phrs.2000.0662.Elmansy RA, Seleem HS, Mahmoud AR, Hassanein EHM, Ali FEM. Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study. Anat Rec (Hoboken). 2021 Mar;304(3):647–661. doi: 10.1002/ar.24482.Elmansy RA, Seleem HS, Mahmoud AR, Hassanein EHM, Ali FEM. Rebamipide potentially mitigates methotrexate-induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study. Anat Rec (Hoboken). 2021 Mar;304(3):647–661. doi: 10.1002/ar.24482.Zaky HS, Abdel-Sattar SA, Allam A, Ahmed HI. Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and β-catenin/cyclin D 1 pathways. Drug Chem Toxicol. 2023 Nov;46(5):851–863. doi: 10.1080/01480545.2022.2104867.Zaky HS, Abdel-Sattar SA, Allam A, Ahmed HI. Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and β-catenin/cyclin D 1 pathways. Drug Chem Toxicol. 2023 Nov;46(5):851–863. doi: 10.1080/01480545.2022.2104867.Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association.Gastroenterology. 2017 Mar;152(4):706–715. doi: 10.1053/j.gastro.2017.01.031.Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association.Gastroenterology. 2017 Mar;152(4):706–715. doi: 10.1053/j.gastro.2017.01.031.Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology 2022;162:1334–1342. doi: 10.1053/j.gastro.2021.12.247.Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology 2022;162:1334–1342. doi: 10.1053/j.gastro.2021.12.247.

The authors declare that there are no conflicts of interest present.