The use of anti-ulcer agents and the risk of chronic kidney disease: a meta-analysis
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.
KeywordsAnti-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 was obtained from all individual participants included in the study.
- 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. https://doi.org/10.1097/ccm.0000000000001819 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1097/ccm.0000000000002461 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1016/j.jcrc.2017.08.036 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1097/TA.0b013e31815e40b5 CrossRefPubMedGoogle Scholar
- 11.Moledina DG, Perazella MA (2017) Drug-induced acute interstitial nephritis. Clin J Am Soc Nephrol 60(2):804–817Google Scholar
- 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 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 15 Mar 2017
- 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. https://doi.org/10.1002/pds.3329 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1053/j.gastro.2017.05.046 CrossRefPubMedGoogle Scholar
- 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. https://doi.org/10.1093/ndt/gfw470 CrossRefGoogle Scholar