Skip to main content
Top
Published in: Digestive Diseases and Sciences 10/2017

01-10-2017 | Original Article

Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis

Authors: Karn Wijarnpreecha, Charat Thongprayoon, Supavit Chesdachai, Panadeekarn Panjawatanana, Patompong Ungprasert, Wisit Cheungpasitporn

Published in: Digestive Diseases and Sciences | Issue 10/2017

Login to get access

Abstract

Background/Aims

The aim of this meta-analysis was to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton-pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs).

Methods

Comprehensive literature review was conducted utilizing MEDLINE and EMBASE databases through April 2017 to identify all studies that investigated the risks of CKD or ESRD in patients taking PPIs/H2RAs versus those without PPIs/H2RAs. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067252).

Results

Five studies with 536,902 participants were patients were identified and included in the data analysis. When compared with non-PPIs users, the pooled risk ratio (RR) of CKD or ESRD in patients with PPI use was 1.33 (95% CI 1.18–1.51). Pre-specified subgroup analysis (stratified by CKD or ESRD status) demonstrated pooled RRs of 1.22 (95% CI 1.14–1.30) for association between PPI use and CKD and 1.88 (95% CI 1.71–2.06) for association between PPI use and ESRD, respectively. However, there was no association between the use of H2RAs and CKD with a pooled RR of 1.02 (95% CI 0.83–1.25). When compared with the use of H2RAs, the pooled RR of CKD in patients with PPI use was 1.29 (95% CI 1.22–1.36).

Conclusions

Our study demonstrates statistically significant 1.3-fold increased risks of CKD and ESRD in patients using PPIs, but not in patients using H2RAs.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–352.CrossRefPubMed Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet. 2013;382:339–352.CrossRefPubMed
3.
go back to reference Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305.CrossRefPubMed Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305.CrossRefPubMed
4.
5.
go back to reference Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–272.CrossRefPubMed Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–272.CrossRefPubMed
6.
go back to reference Muntner P, Coresh J, Powe NR, Klag MJ. The contribution of increased diabetes prevalence and improved myocardial infarction and stroke survival to the increase in treated end-stage renal disease. J Am Soc Nephrol. 2003;14:1568–1577.CrossRefPubMed Muntner P, Coresh J, Powe NR, Klag MJ. The contribution of increased diabetes prevalence and improved myocardial infarction and stroke survival to the increase in treated end-stage renal disease. J Am Soc Nephrol. 2003;14:1568–1577.CrossRefPubMed
7.
go back to reference Chalmers L, Kaskel FJ, Bamgbola O. The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. Adv Chronic Kidney Dis. 2006;13:352–364.CrossRefPubMed Chalmers L, Kaskel FJ, Bamgbola O. The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. Adv Chronic Kidney Dis. 2006;13:352–364.CrossRefPubMed
8.
go back to reference Lastra G, Manrique C, Sowers JR. Obesity, cardiometabolic syndrome, and chronic kidney disease: the weight of the evidence. Adv Chronic Kidney Dis. 2006;13:365–373.CrossRefPubMed Lastra G, Manrique C, Sowers JR. Obesity, cardiometabolic syndrome, and chronic kidney disease: the weight of the evidence. Adv Chronic Kidney Dis. 2006;13:365–373.CrossRefPubMed
9.
go back to reference Kramer H, Luke A. Obesity and kidney disease: a big dilemma. Curr Opin Nephrol Hypertens. 2007;16:237–241.CrossRefPubMed Kramer H, Luke A. Obesity and kidney disease: a big dilemma. Curr Opin Nephrol Hypertens. 2007;16:237–241.CrossRefPubMed
10.
go back to reference Nast CC. Medication-induced interstitial nephritis in the 21st century. Adv Chronic Kidney Dis. 2017;24:72–79.CrossRefPubMed Nast CC. Medication-induced interstitial nephritis in the 21st century. Adv Chronic Kidney Dis. 2017;24:72–79.CrossRefPubMed
13.
go back to reference Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5:219–232.CrossRefPubMedPubMedCentral Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therap Adv Gastroenterol. 2012;5:219–232.CrossRefPubMedPubMedCentral
14.
go back to reference Danziger J, William JH, Scott DJ, et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney Int. 2013;83:692–699.CrossRefPubMed Danziger J, William JH, Scott DJ, et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney Int. 2013;83:692–699.CrossRefPubMed
15.
go back to reference Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170:784–790.CrossRefPubMed Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170:784–790.CrossRefPubMed
16.
go back to reference Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301:2120–2128.CrossRefPubMed Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301:2120–2128.CrossRefPubMed
17.
go back to reference Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–526.CrossRefPubMedPubMedCentral Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519–526.CrossRefPubMedPubMedCentral
18.
go back to reference Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107:1011–1019.CrossRefPubMed Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107:1011–1019.CrossRefPubMed
19.
go back to reference Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310–319.CrossRefPubMedPubMedCentral Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310–319.CrossRefPubMedPubMedCentral
20.
go back to reference Filion KB, Chateau D, Targownik LE, et al. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014;63:552–558.CrossRefPubMed Filion KB, Chateau D, Targownik LE, et al. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014;63:552–558.CrossRefPubMed
21.
go back to reference Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176:172–174.CrossRefPubMed Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176:172–174.CrossRefPubMed
22.
go back to reference Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27:339–347.CrossRefPubMed Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27:339–347.CrossRefPubMed
23.
go back to reference Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37:1237–1241.CrossRefPubMed Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37:1237–1241.CrossRefPubMed
24.
go back to reference Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017;7:e015735.CrossRefPubMed Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of proton pump inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017;7:e015735.CrossRefPubMed
25.
go back to reference Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician. 2017;63:354–364.PubMedPubMedCentral Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician. 2017;63:354–364.PubMedPubMedCentral
26.
go back to reference Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3:E166–E171.CrossRefPubMedPubMedCentral Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3:E166–E171.CrossRefPubMedPubMedCentral
27.
go back to reference Ardalan M-R, Ebrahimzade V, Kasra A, Tamadon M-R. Interstitial nephritis; a rising threat with different aspects. Ann Res Dial. 2017;2:e02. Ardalan M-R, Ebrahimzade V, Kasra A, Tamadon M-R. Interstitial nephritis; a rising threat with different aspects. Ann Res Dial. 2017;2:e02.
28.
go back to reference Hedaiaty M, Amiri A, Amiri A. Impact of proton pump inhibitors on renal function and structure; new concepts. J Prev Epidemiol. 2017;2:e05. Hedaiaty M, Amiri A, Amiri A. Impact of proton pump inhibitors on renal function and structure; new concepts. J Prev Epidemiol. 2017;2:e05.
29.
go back to reference Fisher AA, Le Couteur DG. Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. Drug Saf. 2001;24:39–57.CrossRefPubMed Fisher AA, Le Couteur DG. Nephrotoxicity and hepatotoxicity of histamine H2 receptor antagonists. Drug Saf. 2001;24:39–57.CrossRefPubMed
30.
31.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
32.
go back to reference Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–605.CrossRefPubMed Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–605.CrossRefPubMed
33.
35.
go back to reference Arora P, Gupta A, Golzy M, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17:112.CrossRefPubMedPubMedCentral Arora P, Gupta A, Golzy M, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17:112.CrossRefPubMedPubMedCentral
36.
go back to reference 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. 2016;95:e3363.CrossRefPubMedPubMedCentral 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. 2016;95:e3363.CrossRefPubMedPubMedCentral
37.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
38.
go back to reference Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16:e228–e234.PubMed Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16:e228–e234.PubMed
39.
go back to reference Hedaiaty M, Amiri A, Amiri M. Impact of proton pump inhibitors on renal function and structure; new concepts. J Prev Epidemiol. 2017;2:e05. Hedaiaty M, Amiri A, Amiri M. Impact of proton pump inhibitors on renal function and structure; new concepts. J Prev Epidemiol. 2017;2:e05.
40.
go back to reference Amiri M. Renal injury by administration of proton pump inhibitors. J Renal Endocrinol. 2017;3:e06. Amiri M. Renal injury by administration of proton pump inhibitors. J Renal Endocrinol. 2017;3:e06.
41.
go back to reference Hedaiaty M, Tamadon M, Amiri A, Mahmoodnia L. Proton-pump inhibitors and risk of renal disease. J Nephropharmacol. 2017;6:33–37. Hedaiaty M, Tamadon M, Amiri A, Mahmoodnia L. Proton-pump inhibitors and risk of renal disease. J Nephropharmacol. 2017;6:33–37.
42.
go back to reference 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 Dev Ther. 2017;11:1291–1299.CrossRef 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 Dev Ther. 2017;11:1291–1299.CrossRef
43.
go back to reference Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant. 2004;19:2778–2783.CrossRefPubMed Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant. 2004;19:2778–2783.CrossRefPubMed
44.
go back to reference Van Laecke S, Nagler EV, Verbeke F, Van Biesen W, Vanholder R. Hypomagnesemia and the risk of death and GFR decline in chronic kidney disease. Am J Med. 2013;126:825–831.CrossRefPubMed Van Laecke S, Nagler EV, Verbeke F, Van Biesen W, Vanholder R. Hypomagnesemia and the risk of death and GFR decline in chronic kidney disease. Am J Med. 2013;126:825–831.CrossRefPubMed
Metadata
Title
Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis
Authors
Karn Wijarnpreecha
Charat Thongprayoon
Supavit Chesdachai
Panadeekarn Panjawatanana
Patompong Ungprasert
Wisit Cheungpasitporn
Publication date
01-10-2017
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 10/2017
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-017-4725-5

Other articles of this Issue 10/2017

Digestive Diseases and Sciences 10/2017 Go to the issue