International Urology and Nephrology

, Volume 50, Issue 10, pp 1835–1843 | Cite as

The use of anti-ulcer agents and the risk of chronic kidney disease: a meta-analysis

  • Jing Sun
  • Hongjun Sun
  • Meiyu Cui
  • Zhijian Sun
  • Wenyue Li
  • Jianxin Wei
  • Shuhua ZhouEmail author
Nephrology - Review



We conducted a meta-analysis to explore the association between the use of different anti-ulcer agents and the risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), and decline in glomerular filtration rate (GFR) in various study populations.


PubMed, Embase, and the Cochrane Library were searched for relevant entries up to July 1, 2017. The primary outcomes of the meta-analysis were risk ratios (RRs) of CKD, ESRD, and decline in GFR. We also investigated the heterogeneity of the meta-analysis by subgroup analysis and meta-regression analysis.


A total of 662,624 individuals were enrolled in five trials. Compared with non-PPI users, PPI users had a higher trend of CKD (RR = 1.16, 95% CI 1.07–1.25, P < 0.001), especially ESRD (RR = 1.81, 95% CI 1.59–2.06, P < 0.001). There was an elevated risk of adverse renal outcome among participants receiving PPI and not H2RA (CKD: RR = 1.28, 95% CI 1.24–1.33, P < 0.001; ESRD: RR = 1.39, 95% CI 1.17–1.64, P < 0.001; GFR: RR = 1.31, 95% CI 1.26–1.36, P < 0.001). However, H2RA users were not associated with CKD when compared with non-H2RA users (RR = 1.02, 95% CI 0.83–1.25, P = 0.855). In subgroup analysis, the average age of individuals and drug dosage had no influence on the risk of CKD, while duration of PPI exposure from 31 to 720 days is a potential factor in progression to ESRD (P < 0.001).


Chronic PPI use, but not H2RAs, is associated with deterioration in kidney function.


Anti-ulcer agents PPI H2RA Chronic kidney disease Meta-analysis 


Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Selvanderan SP, Summers MJ, Finnis ME, Plummer MP, Abdelhamid YA, Anderson MB, Chapman MJ, Rayner CK, Deane AM (2016) Pantoprazole or placebo for stress ulcer prophylaxis (POP-UP)): randomized double-blind exploratory study. Crit Care Med 44(10):1842–1850. CrossRefPubMedGoogle Scholar
  2. 2.
    Alhazzani W, Guyatt G, Alshahrani M, Deane AM, Marshall JC, Hall R, Muscedere J, English SW, Lauzier F, Thabane L, Arabi YM, Karachi T, Rochwerg B, Finfer S, Daneman N, Alshamsi F, Zytaruk N, Heel-Ansdell D, Cook D (2017) Withholding pantoprazole for stress ulcer prophylaxis in critically ill patients: a pilot randomized clinical trial and meta-analysis. Crit Care Med 45(7):1121–1129. CrossRefPubMedGoogle Scholar
  3. 3.
    El-Kersh K, Jalil B, McClave SA, Cavallazzi R, Guardiola J, Guilkey K, Persaud AK, Furmanek SP, Guinn BE, Wiemken TL, Alhariri BC, Kellie SP, Saad M (2017) Enteral nutrition as stress ulcer prophylaxis in critically ill patients: a randomized controlled exploratory study. J Crit Care 43:108–113. CrossRefPubMedGoogle Scholar
  4. 4.
    Wu H, Jing Q, Wang J, Guo X (2011) Pantoprazole for the prevention of gastrointestinal bleeding in high-risk patients with acute coronary syndromes. J Crit Care 26(4):e431–e436. CrossRefGoogle Scholar
  5. 5.
    MacLaren R, Campbell J (2014) Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients. Crit Care Med 42(4):809–815CrossRefPubMedGoogle Scholar
  6. 6.
    Somberg L, Morris J Jr, Fantus R, Graepel J, Field BG, Lynn R, Karlstadt R (2008) Intermittent intravenous pantoprazole and continuous cimetidine infusion: effect on gastric ph control in critically ill patients at risk of developing stress-related mucosal disease. J Trauma 64(5):1202–1210. CrossRefPubMedGoogle Scholar
  7. 7.
    Bian J, Wang A, Lin J, Wu L, Huang H, Wang S, Yang X, Lu X, Xu Y, Zhao H (2017) Association between proton pump inhibitors and hepatic encephalopathy: a meta-analysis. Medicine 96(17):e6723. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wang Y-F, Chen Y-T, Luo J-C, Chen T-J, Wu J-C, Wang S-J (2017) Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: a nationwide population-based study. Am J Gastroenterol 112(7):1084–1093. CrossRefPubMedGoogle Scholar
  9. 9.
    Zhu W, Hong K (2017) Potential cardiovascular risks of proton pump inhibitors in the general population. Int Heart J 58(2):163–166CrossRefPubMedGoogle Scholar
  10. 10.
    Harmark L, van der Wiel HE, de Groot MC, van Grootheest AC (2007) Proton pump inhibitor-induced acute interstitial nephritis. Br J Clin Pharmacol 64(6):819–823. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Moledina DG, Perazella MA (2017) Drug-induced acute interstitial nephritis. Clin J Am Soc Nephrol 60(2):804–817Google Scholar
  12. 12.
    Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME (2016) Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 176(2):238–246. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Arora P, Gupta A, Golzy M, Patel N, Carter RL, Jalal K, Lohr JW (2016) Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol 17(1):112. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Wells GA, Shea B, O’Connell D, Peterson J Welch V, Losos M, Tugwell P (2017) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available from Accessed 15 Mar 2017
  15. 15.
    Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, Paterson JM, Juurlink DN (2015) Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open 3(2):E166–E171. CrossRefGoogle Scholar
  17. 17.
    Leonard CE, Freeman CP, Newcomb CW, Reese PP, Herlim M, Bilker WB, Hennessy S, Strom BL (2012) Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury. Pharmacoepidemiol Drug Saf 21(11):1155–1172. CrossRefPubMedGoogle Scholar
  18. 18.
    Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z (2016) Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol 27(10):3153–3163. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z (2017) Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 91(6):1482–1494. CrossRefPubMedGoogle Scholar
  20. 20.
    Klatte DCF, Gasparini A, Xu H, de Deco P, Trevisan M, Johansson ALV, Wettermark B, Arnlov J, Janmaat CJ, Lindholm B, Dekker FW, Coresh J, Grams ME, Carrero JJ (2017) Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology. CrossRefPubMedGoogle Scholar
  21. 21.
    Peng Y-C, Lin C-L, Yeh H-Z, Chang C-S, Wu Y-L, Kao C-H (2016) Association between the use of proton pump inhibitors and the risk of ESRD in renal diseases. Medicine 95(15):e3363. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Nochaiwong S, Ruengorn C, Awiphan R, Koyratkoson K, Chaisai C, Noppakun K, Chongruksut W, Thavorn K (2017) The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. CrossRefGoogle Scholar
  23. 23.
    Yang Y, George KC, Shang W, Zeng R, Ge S, Xu G (2017) Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies. Drug Des Dev Ther 11:1291–1299. CrossRefGoogle Scholar
  24. 24.
    Muriithi AK, Leung N, Valeri AM, Cornell LD, Sethi S, Fidler ME, Nasr SH (2015) Clinical characteristics, causes and outcomes of acute interstitial nephritis in the elderly. Kidney Int 87(2):458–464. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Jing Sun
    • 1
  • Hongjun Sun
    • 2
  • Meiyu Cui
    • 3
  • Zhijian Sun
    • 4
  • Wenyue Li
    • 1
  • Jianxin Wei
    • 1
  • Shuhua Zhou
    • 1
    Email author
  1. 1.Department of NephrologyDezhou People’s HospitalDezhouPeople’s Republic of China
  2. 2.Department of Blood TransfusionDezhou People’s HospitalDezhouPeople’s Republic of China
  3. 3.Department of NephrologyQianfoshan HospitalJinanPeople’s Republic of China
  4. 4.Department of General SurgeryDezhou People’s HospitalDezhouPeople’s Republic of China

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