Skip to main content
Top
Published in: BMC Nephrology 1/2016

Open Access 01-12-2016 | Research article

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

Authors: Pradeep Arora, Anu Gupta, Mojgan Golzy, Nilang Patel, Randolph L. Carter, Kabir Jalal, James W. Lohr

Published in: BMC Nephrology | Issue 1/2016

Login to get access

Abstract

Background

Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death.

Methods

Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables.

Results

A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case–control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05–1.16) and mortality (OR 1.76, 95 % CI 1.67–1.84) among patients taking PPIs versus those not on PPIs.

Conclusions

Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.
Literature
1.
go back to reference Heidelbaugh J, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therapy Adv Gastroenterol. 2012;5:219–32.CrossRef Heidelbaugh J, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Therapy Adv Gastroenterol. 2012;5:219–32.CrossRef
2.
go back to reference Friedenberg FK, Hanlon A, Vanar V, Nehemia D, Mekapati J, Nelson DB, et al. Trends in gastroesophageal reflux disease as measured by the National Ambulatory Medical Care Survey. Dig Dis Sci. 2010;55:1911–7.CrossRefPubMed Friedenberg FK, Hanlon A, Vanar V, Nehemia D, Mekapati J, Nelson DB, et al. Trends in gastroesophageal reflux disease as measured by the National Ambulatory Medical Care Survey. Dig Dis Sci. 2010;55:1911–7.CrossRefPubMed
4.
go back to reference Maggio M, Corsonello A, Ceda GP, Cattabiani C, Lauretani F, Butto V, et al. Proton Pump Inhibitors and Risk of 1-Year Mortality and hospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173:518–23.CrossRefPubMed Maggio M, Corsonello A, Ceda GP, Cattabiani C, Lauretani F, Butto V, et al. Proton Pump Inhibitors and Risk of 1-Year Mortality and hospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173:518–23.CrossRefPubMed
5.
go back to reference Charlot M, Grove EL, Hansen PR, Olesen JB, Ahlehoff O, Selmer C, et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ. 2011;342:d2690. doi:10.1136/bmj.d2690.CrossRefPubMedPubMedCentral Charlot M, Grove EL, Hansen PR, Olesen JB, Ahlehoff O, Selmer C, et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ. 2011;342:d2690. doi:10.​1136/​bmj.​d2690.CrossRefPubMedPubMedCentral
6.
go back to reference Bell JS, Strandberg TE, Teramura-Gronblad M, Laurila JV, Tilvis RS, Pitkala KH. Use of proton pump inhibitors and mortality among institutionalized older people. Arch Intern Med. 2010;170:1604–5.PubMed Bell JS, Strandberg TE, Teramura-Gronblad M, Laurila JV, Tilvis RS, Pitkala KH. Use of proton pump inhibitors and mortality among institutionalized older people. Arch Intern Med. 2010;170:1604–5.PubMed
7.
go back to reference Brewster UC, Perazella MA. Acute kidney injury following proton pump inhibitor therapy. Kidney Int. 2007;71:589–93.CrossRefPubMed Brewster UC, Perazella MA. Acute kidney injury following proton pump inhibitor therapy. Kidney Int. 2007;71:589–93.CrossRefPubMed
8.
go back to reference Prentice RL, Pyke R. Logistic Incidence Models and Case-Control Studies. Biometrika. 1979;66:403–11.CrossRef Prentice RL, Pyke R. Logistic Incidence Models and Case-Control Studies. Biometrika. 1979;66:403–11.CrossRef
9.
go back to reference Anderson JA. Separate sample logistic discrimination. Biometrika. 1972;59:19–35.CrossRef Anderson JA. Separate sample logistic discrimination. Biometrika. 1972;59:19–35.CrossRef
10.
go back to reference Breslow NE, Powers W. Are there two logistic regressions for retrospective studies? Biometrics. 1978;34:100–5.CrossRefPubMed Breslow NE, Powers W. Are there two logistic regressions for retrospective studies? Biometrics. 1978;34:100–5.CrossRefPubMed
11.
go back to reference Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol. 2007;68:65–72.CrossRefPubMed Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol. 2007;68:65–72.CrossRefPubMed
13.
go back to reference Simpson IJ, Marshall MR, Pilmore H, Manley P, William L, Thein H, et al. Proton pump inhibitor and acute interstitial nephritis: report and analysis of 15 cases. Nephrology (Carlton). 2006;11:381–5.CrossRef Simpson IJ, Marshall MR, Pilmore H, Manley P, William L, Thein H, et al. Proton pump inhibitor and acute interstitial nephritis: report and analysis of 15 cases. Nephrology (Carlton). 2006;11:381–5.CrossRef
14.
go back to reference 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;86:837–44.CrossRefPubMedPubMedCentral 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;86:837–44.CrossRefPubMedPubMedCentral
15.
go back to reference Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol. 2006;4:597–604.CrossRefPubMed Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol. 2006;4:597–604.CrossRefPubMed
16.
go back to reference Sierra F, Suarez M, Rey M, Vela MF. Systematic review: proton pump inhibitor associated acute interstitial nephritis. Aliment Pharmacol Ther. 2007;26:545–53.CrossRefPubMed Sierra F, Suarez M, Rey M, Vela MF. Systematic review: proton pump inhibitor associated acute interstitial nephritis. Aliment Pharmacol Ther. 2007;26:545–53.CrossRefPubMed
17.
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. [epub ahead of print]. 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. [epub ahead of print].
18.
go back to reference 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(2):238–46.CrossRefPubMed 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(2):238–46.CrossRefPubMed
19.
go back to reference Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis. 2000;35(4 Suppl 1):117–31.CrossRef Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis. 2000;35(4 Suppl 1):117–31.CrossRef
20.
go back to reference Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y. Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 2007;458:48–56.CrossRefPubMed Mazur A, Maier JA, Rock E, Gueux E, Nowacki W, Rayssiguier Y. Magnesium and the inflammatory response: potential physiopathological implications. Arch Biochem Biophys. 2007;458:48–56.CrossRefPubMed
21.
go back to reference Wolf FI, Trapani V, Simonacci M, Ferré S, Maier JA. Magnesium deficiency and endothelial dysfunction: is oxidative stress involved? Magnes Res. 2008;21:58–64.PubMed Wolf FI, Trapani V, Simonacci M, Ferré S, Maier JA. Magnesium deficiency and endothelial dysfunction: is oxidative stress involved? Magnes Res. 2008;21:58–64.PubMed
22.
go back to reference Corsonello A, Ientile R, Buemi M, Cucinotta D, Mauro VN, Macaione S, et al. Serum ionized magnesium levels in type 2 diabetic patients with microalbuminuria or clinical proteinuria. Am J Nephrol. 2000;20:187–92.CrossRefPubMed Corsonello A, Ientile R, Buemi M, Cucinotta D, Mauro VN, Macaione S, et al. Serum ionized magnesium levels in type 2 diabetic patients with microalbuminuria or clinical proteinuria. Am J Nephrol. 2000;20:187–92.CrossRefPubMed
23.
go back to reference Pham PC, Pham PM, Pham PA, Pham SV, Pham HV, Miller JM, et al. Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2. Clin Nephrol. 2005;63:429–36.CrossRefPubMed Pham PC, Pham PM, Pham PA, Pham SV, Pham HV, Miller JM, et al. Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2. Clin Nephrol. 2005;63:429–36.CrossRefPubMed
24.
go back to reference Sakaguchi Y, Shoji T, Hayashi T, Suzuki A, Shimizu M, Mitsumoto K, et al. Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease. Diabetes Care. 2012;35:1591–7.CrossRefPubMedPubMedCentral Sakaguchi Y, Shoji T, Hayashi T, Suzuki A, Shimizu M, Mitsumoto K, et al. Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease. Diabetes Care. 2012;35:1591–7.CrossRefPubMedPubMedCentral
25.
go back to reference Matsuzaki H, Ohdachi J, Fuchigami M, Masuyama R, Uehara M, Nakamura K, et al. Changes in N-acetyl-beta-D-glucosaminidase activity in the urine and urinary albumin excretion in magnesium deficient rats. Biosci Biotechnol Biochem. 2002;66:192–4.CrossRefPubMed Matsuzaki H, Ohdachi J, Fuchigami M, Masuyama R, Uehara M, Nakamura K, et al. Changes in N-acetyl-beta-D-glucosaminidase activity in the urine and urinary albumin excretion in magnesium deficient rats. Biosci Biotechnol Biochem. 2002;66:192–4.CrossRefPubMed
Metadata
Title
Proton pump inhibitors are associated with increased risk of development of chronic kidney disease
Authors
Pradeep Arora
Anu Gupta
Mojgan Golzy
Nilang Patel
Randolph L. Carter
Kabir Jalal
James W. Lohr
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2016
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-016-0325-4

Other articles of this Issue 1/2016

BMC Nephrology 1/2016 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.