{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:27:59Z","timestamp":1790634479943,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:p>\n                    The association between proton pump inhibitors (PPI) use and risk of acute interstitial nephritis has been described. However, whether exposure to PPI associates with incident CKD, CKD progression, or ESRD is not known. We used Department of Veterans Affairs national databases to build a primary cohort of new users of PPI (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    =173,321) and new users of histamine H\n                    <jats:sub>2<\/jats:sub>\n                    -receptor antagonists (H\n                    <jats:sub>2<\/jats:sub>\n                    blockers;\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    =20,270) and followed these patients over 5 years to ascertain renal outcomes. In adjusted Cox survival models, the PPI group, compared with the H\n                    <jats:sub>2<\/jats:sub>\n                    blockers group, had an increased risk of incident eGFR&lt;60 ml\/min per 1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    and of incident CKD (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.18 to 1.26; and HR, 1.28; 95% CI, 1.23 to 1.34, respectively). Patients treated with PPI also had a significantly elevated risk of doubling of serum creatinine level (HR, 1.53; 95% CI, 1.42 to 1.65), of eGFR decline &gt;30% (HR, 1.32; 95% CI, 1.28 to 1.37), and of ESRD (HR, 1.96; 95% CI, 1.21 to 3.18). Furthermore, we detected a graded association between duration of PPI exposure and risk of renal outcomes among those exposed to PPI for 31\u201390, 91\u2013180, 181\u2013360, and 361\u2013720 days compared with those exposed for \u226430 days. Examination of risk of renal outcomes in 1:1 propensity score-matched cohorts of patients taking H\n                    <jats:sub>2<\/jats:sub>\n                    blockers versus patients taking PPI and patients taking PPI versus controls yielded consistent results. Our results suggest that PPI exposure associates with increased risk of incident CKD, CKD progression, and ESRD.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015121377","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T22:29:47Z","timestamp":1460672987000},"page":"3153-3163","source":"Crossref","is-referenced-by-count":286,"title":["Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD"],"prefix":"10.1681","volume":"27","author":[{"given":"Yan","family":"Xie","sequence":"first","affiliation":[{"name":"Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bowe","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xian","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System,"},{"name":"Department of Biostatistics, College for Public Health and Social Justice, Saint Louis University,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumitra","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyad","family":"Al-Aly","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Center, Veterans Affairs Saint Louis Health Care System,"},{"name":"Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri;"},{"name":"Division of Nephrology, Department of Medicine, Veterans Affairs Saint Louis Health Care System, Saint Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"E166","DOI":"10.9778\/cmajo.20140074","article-title":"Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study.","volume":"3","author":"Antoniou","year":"2015","journal-title":"CMAJ Open"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1471-2369-14-150","article-title":"Proton pump inhibitors and acute kidney injury: a nested case-control study.","volume":"14","author":"Klepser","year":"2013","journal-title":"BMC Nephrol"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/ki.2014.74","article-title":"A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use.","volume":"86","author":"Blank","year":"2014","journal-title":"Kidney Int"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1038\/ki.2010.89","article-title":"Acute interstitial nephritis.","volume":"77","author":"Praga","year":"2010","journal-title":"Kidney Int"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5414\/CNP68065","article-title":"Proton pump inhibitors and the kidney: critical review.","volume":"68","author":"Brewster","year":"2007","journal-title":"Clin Nephrol"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nrneph.2010.71","article-title":"Drug-induced acute interstitial nephritis.","volume":"6","author":"Perazella","year":"2010","journal-title":"Nat Rev Nephrol"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1046\/j.1523-1755.2001.060002804.x","article-title":"Drug-induced acute interstitial nephritis.","volume":"60","author":"Rossert","year":"2001","journal-title":"Kidney Int"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1001\/jamainternmed.2015.7193","article-title":"Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease.","volume":"176","author":"Lazarus","year":"2016","journal-title":"JAMA Intern Med"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1001\/jamainternmed.2015.7927","article-title":"Adverse Effects Associated With Proton Pump Inhibitors.","volume":"176","author":"Schoenfeld","year":"2016","journal-title":"JAMA Intern Med"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1136\/bmj.39406.449456.BE","article-title":"Overprescribing proton pump inhibitors.","volume":"336","author":"Forgacs","year":"2008","journal-title":"BMJ"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/j.1365-2036.2005.02454.x","article-title":"Long-term use of acid suppression started inappropriately during hospitalization.","volume":"21","author":"Zink","year":"2005","journal-title":"Aliment Pharmacol Ther"},{"key":"B13-20231016","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/ndt\/18.3.570","article-title":"Overuse of acid suppressant drugs in patients with chronic renal failure.","volume":"18","author":"Strid","year":"2003","journal-title":"Nephrol Dial Transplant"},{"key":"B14-20231016","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/ki.2012.452","article-title":"Proton-pump inhibitor use is associated with low serum magnesium concentrations.","volume":"83","author":"Danziger","year":"2013","journal-title":"Kidney Int"},{"key":"B15-20231016","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1053\/j.ajkd.2015.05.012","article-title":"Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.","volume":"66","author":"Kieboom","year":"2015","journal-title":"Am J Kidney Dis"},{"key":"B16-20231016","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1056\/NEJMp1014427","article-title":"Developing the Sentinel System--a national resource for evidence development.","volume":"364","author":"Behrman","year":"2011","journal-title":"N Engl J Med"},{"issue":"Suppl 1","key":"B17-20231016","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/pds.2311","article-title":"The US Food and Drug Administration\u2019s Sentinel Initiative: expanding the horizons of medical product safety.","volume":"21","author":"Robb","year":"2012","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1056\/NEJMp1401664","article-title":"Mini-Sentinel and regulatory science--big data rendered fit and functional.","volume":"370","author":"Psaty","year":"2014","journal-title":"N Engl J Med"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(06)68041-0","article-title":"Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis.","volume":"367","author":"Hackam","year":"2006","journal-title":"Lancet"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1479-5876-5-21","article-title":"In support of descriptive studies; relevance to translational research.","volume":"5","author":"Marincola","year":"2007","journal-title":"J Transl Med"},{"key":"B21-20231016","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/j.1365-2125.2007.02927.x","article-title":"Proton pump inhibitor-induced acute interstitial nephritis.","volume":"64","author":"H\u00e4rmark","year":"2007","journal-title":"Br J Clin Pharmacol"},{"key":"B22-20231016","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1586\/17512433.2015.1045489","article-title":"Review of select causes of drug-induced AKI.","volume":"8","author":"Perazella","year":"2015","journal-title":"Expert Rev Clin Pharmacol"},{"key":"B23-20231016","doi-asserted-by":"crossref","first-page":"520","DOI":"10.2215\/CJN.06711208","article-title":"The nexus of acute kidney injury, chronic kidney disease, and World Kidney Day 2009.","volume":"4","author":"Okusa","year":"2009","journal-title":"Clin J Am Soc Nephrol"},{"key":"B24-20231016","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1681\/ASN.2007080837","article-title":"Acute kidney injury increases risk of ESRD among elderly.","volume":"20","author":"Ishani","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B25-20231016","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/ki.2011.379","article-title":"Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis.","volume":"81","author":"Coca","year":"2012","journal-title":"Kidney Int"},{"key":"B26-20231016","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.amjmed.2013.02.036","article-title":"Hypomagnesemia and the risk of death and GFR decline in chronic kidney disease.","volume":"126","author":"Van Laecke","year":"2013","journal-title":"Am J Med"},{"key":"B27-20231016","doi-asserted-by":"crossref","first-page":"429","DOI":"10.5414\/CNP63429","article-title":"Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2.","volume":"63","author":"Pham","year":"2005","journal-title":"Clin Nephrol"},{"key":"B28-20231016","doi-asserted-by":"crossref","first-page":"375","DOI":"10.5414\/CNP71375","article-title":"The link between lower serum magnesium and kidney function in patients with diabetes mellitus Type 2 deserves a closer look.","volume":"71","author":"Pham","year":"2009","journal-title":"Clin Nephrol"},{"key":"B29-20231016","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2337\/dc12-0226","article-title":"Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease.","volume":"35","author":"Sakaguchi","year":"2012","journal-title":"Diabetes Care"},{"key":"B30-20231016","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1093\/ndt\/gfh831","article-title":"Low serum magnesium is associated with decreased graft survival in patients with chronic cyclosporin nephrotoxicity.","volume":"20","author":"Holzmacher","year":"2005","journal-title":"Nephrol Dial Transplant"},{"key":"B31-20231016","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1038\/ki.2014.331","article-title":"Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease.","volume":"87","author":"Tin","year":"2015","journal-title":"Kidney Int"},{"key":"B32-20231016","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.annepidem.2014.01.004","article-title":"Proton-pump inhibitor use and hip fractures in men: a population-based case-control study.","volume":"24","author":"Adams","year":"2014","journal-title":"Ann Epidemiol"},{"key":"B34-20231016","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/0895-4356(94)90170-8","article-title":"Evidence of the depletion of susceptibles effect in non-experimental pharmacoepidemiologic research.","volume":"47","author":"Moride","year":"1994","journal-title":"J Clin Epidemiol"},{"key":"B35-20231016","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1161\/CIRCOUTCOMES.113.000359","article-title":"Propensity score methods for confounding control in nonexperimental research.","volume":"6","author":"Brookhart","year":"2013","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"B36-20231016","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jclinepi.2005.07.004","article-title":"A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.","volume":"59","author":"St\u00fcrmer","year":"2006","journal-title":"J Clin Epidemiol"},{"key":"B37-20231016","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1093\/ndt\/gfh104","article-title":"Propensity scores: help or hype?","volume":"19","author":"Winkelmayer","year":"2004","journal-title":"Nephrol Dial Transplant"},{"key":"B38-20231016","doi-asserted-by":"crossref","first-page":"e0149283","DOI":"10.1371\/journal.pone.0149283","article-title":"Renal Function Trajectories in Patients with Prior Improved eGFR Slopes and Risk of Death.","volume":"11","author":"Xie","year":"2016","journal-title":"PLoS One"},{"issue":"Suppl","key":"B39-20231016","first-page":"E4","article-title":"Veterans Health Administration inpatient and outpatient care data: an overview.","volume":"5","author":"Murphy","year":"2002","journal-title":"Eff Clin Pract"},{"key":"B40-20231016","first-page":"35","article-title":"Veterans Affairs Research and Development: using science to improve health care for veterans.","volume":"69","author":"Oddone","year":"2008","journal-title":"N C Med J"},{"key":"B43-20231016","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ki.2012.418","article-title":"Prediction of renal end points in chronic kidney disease.","volume":"83","author":"Al-Aly","year":"2013","journal-title":"Kidney Int"},{"key":"B44-20231016","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1001\/jama.2014.6634","article-title":"Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.","volume":"311","author":"Coresh","year":"2014","journal-title":"JAMA"},{"key":"B46-20231016","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.2215\/CJN.09320913","article-title":"Relation of serum lipids and lipoproteins with progression of CKD: The CRIC study.","volume":"9","author":"Rahman","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"B47-20231016","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate.","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B48-20231016","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1007\/s11606-013-2345-0","article-title":"Proton pump inhibitor prescriptions and subsequent use in US veterans diagnosed with gastroesophageal reflux disease.","volume":"28","author":"Gawron","year":"2013","journal-title":"J Gen Intern Med"},{"key":"B49-20231016","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.2215\/CJN.04480415","article-title":"Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKD.","volume":"10","author":"Xie","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B50-20231016","article-title":"Bowe B, Xian H, Balasubramanian S, Al-Aly Z: Estimated GFR Trajectories of People Entering Stage 4 CKD and Subsequent Kidney Disease Outcomes and Mortality [publsihed online ahead of print March 4, 2016].","author":"Xie","journal-title":"Am J Kidney Dis"},{"key":"B51-20231016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/pds.3334","article-title":"The incident user design in comparative effectiveness research.","volume":"22","author":"Johnson","year":"2013","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"B52-20231016","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies.","volume":"46","author":"Austin","year":"2011","journal-title":"Multivariate Behav Res"},{"key":"B53-20231016","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1002\/sim.2580","article-title":"A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study.","volume":"26","author":"Austin","year":"2007","journal-title":"Stat Med"},{"key":"B54-20231016","author":"Siew"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201610000-00025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:27:48Z","timestamp":1786130868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201610000-00025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,14]]},"references-count":49,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2015121377","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726288701.793519221","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,14]]}}}