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Khan A, Mushtaq M, Movva G, Sohal A, Yang J. Gastrointestinal disease in end-stage renal disease. World J Nephrol 2025; 14:101917. [PMID: 40134640 PMCID: PMC11755235 DOI: 10.5527/wjn.v14.i1.101917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 10/24/2024] [Accepted: 01/03/2025] [Indexed: 01/20/2025] Open
Abstract
When kidney function declines to a point where it can no longer maintain life and requires renal replacement therapy (i.e. renal transplant or dialysis), it is called end-stage renal disease (ESRD). Patients with ESRD often experience a range of gastrointestinal (GI) symptoms, with prevalence rates reported as high as 77%-79%. These symptoms and pathologies arise from various factors, including electrolyte imbalance, fluid imbalance, toxin buildup, uremia, medications, dietary and lifestyle restrictions, and the effects of dialysis. GI diseases in patients with renal failure can be further categorized into upper GI, small bowel, and lower GI issues. Common conditions include gastroesophageal reflux disease, nausea and vomiting, dysmotility within the esophagus and stomach, upper GI bleeding, peptic ulcer bleeding, angioectasia, irritable bowel syndrome, mesenteric ischemia, angiodysplasia, diverticular disease, constipation, pancreatitis, and diseases associated with peritoneal dialysis peritonitis and peritoneal stenosis. This review assesses the existing literature on the different GI diseases among individuals with ESRD, shedding light on their pathophysiology and prevalence.
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Affiliation(s)
- Ayesha Khan
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, United States
| | - Muhammad Mushtaq
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, United States
| | - Giri Movva
- Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77550, United States
| | - Aalam Sohal
- Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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Huang CH, Tsai CJ, Su CC, Yen CT, Chen JL, Cheng CL. Accelerated risk of renal disease progression in pre-ESRD patients with proton pump inhibitors use: a nationwide population-based study. BMC Nephrol 2024; 25:469. [PMID: 39716090 DOI: 10.1186/s12882-024-03867-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 11/18/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Although Proton pump inhibitors (PPIs) were mostly prescribed for gastrointestinal (GI) disease widely, there were numerous studies about PPIs and adverse renal outcome. Most evidence was to evaluate the risk of PPIs in patients with normal renal function and in the absence of the moderate to advanced chronic kidney disease (CKD). This study focuses on the accelerated progression of renal function following proton pump inhibitors (PPIs) use, and the increased risks of acute kidney injury (AKI) among moderate to advanced CKD (pre-ESRD) patients. PATIENTS AND METHODS A retrospective cohort study was conducted by including adult patients with chronic kidney disease (CKD) stages 3b to 5 who initiated PPI or H2 blocker (H2B) therapy between 2011 and 2018. The risk of renal events was assessed using the Cox proportional hazard model to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Sensitivity analyses were performed, including propensity score matching, as-treated analysis, and subgroup analysis. RESULTS The cohort comprised 83,432 pre-ESRD patients, with 5,138 treated with H2B and 1,051 with PPIs. The progression to ESRD was significantly more likely in patients using PPIs compared to those using H2B (adjusted HR, 1.495; 95% CI: 1.198-1.867). Specifically, omeprazole (adjusted HR, 1.784; 95% CI: 1.079-2.951) and esomeprazole (adjusted HR, 1.847; 95% CI: 1.332-2.561) were associated with a notably higher risk of ESRD and AKI. CONCLUSIONS The study highlights the significance of the accelerated renal risk, especially for moderate to advanced CKD patients, when prescribing PPIs and to implicate the clinicians prescribed PPIs and H2B in pre-ESRD patients.
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Affiliation(s)
- Chien-Huei Huang
- Department of Pharmacy, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan City, 701, Taiwan
| | - Chih-Jung Tsai
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan City, 701, Taiwan
- Department of General Medicine, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chien-Chou Su
- Clinical Innovation and Research Center, National Cheng Kung University Hospital, No. 138 Sheng Li Road, Tainan, Taiwan
| | - Chi-Tai Yen
- Department of Nephrology, Ministry of Health and Welfare, Tainan Hospital, Tainan, Taiwan
| | - Ju-Ling Chen
- Department of Pharmacy, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan City, 701, Taiwan
| | - Ching-Lan Cheng
- Department of Pharmacy, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
- School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, No. 1 University Road, Tainan City, 701, Taiwan.
- Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan.
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Andhale A, Abraham P, Dhoble P, Desai D, Joshi A, Gupta T, Kothari J, Bhangale N. Renal dysfunction in routine proton-pump inhibitor use may be linked to comorbidities: A real-world observational study. Indian J Gastroenterol 2024; 43:1203-1208. [PMID: 38407788 DOI: 10.1007/s12664-023-01515-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 12/26/2023] [Indexed: 02/27/2024]
Abstract
INTRODUCTION The use of proton-pump inhibitors (PPI) is linked with infrequent but serious adverse events, including acute kidney injury, chronic kidney disease (CKD) and progression of CKD. Data on renal safety in routine use of PPI are more relevant to clinical practice. We studied whether such use of PPI is associated with renal dysfunction. METHODS Patients taking PPI for at least six weeks had serum creatinine tested pre (n = 200) and post (n = 180) recruitment. These patients were then advised to follow-up: those taking PPI for at least 90 days in the next six months (n = 77) and at least another 90 days in the following six months (n = 50), had serum creatinine tested at such follow-up. Renal dysfunction was defined as any increase in serum creatinine level above baseline. RESULTS The 200 patients recruited had mean age 39.6 (SD 9.2) years. Ninety-eight (49%) patients had a history of previous PPI use (median six months; interquartile range [IQR] 3-24). Only 20 (11.1%) patients at six weeks, 11 (14.3%) at six months and six (12%) at one year had increase in creatinine level; a majority of them had less than 0.3 mg/dL increase. Ten of these 20 (six weeks), five of 11 (six months) and five of six (one year) had other risk factors for renal dysfunction. No patient developed CKD during the study period. CONCLUSIONS Mild and non-progressive increase in serum creatinine occurred in 10% to 15% of patients on routine PPI use. A majority of them had other risk factors. Small sample size and short follow-up duration are a few limitations of this study.
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Affiliation(s)
- Adeshkumar Andhale
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Philip Abraham
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India.
| | - Pavan Dhoble
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Devendra Desai
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Anand Joshi
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Tarun Gupta
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Jatin Kothari
- Division of Nephrology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
| | - Nikhil Bhangale
- Division of Gastroenterology, P D Hinduja Hospital and Medical Research Centre, Mahim, Mumbai, 400 016, India
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Murofushi T, Yagi T, Tsuji D, Furushima D, Fujikura T, Itoh K, Kawakami J. Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:4927-4938. [PMID: 38170305 DOI: 10.1007/s00210-023-02890-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 12/04/2023] [Indexed: 01/05/2024]
Abstract
Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.
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Affiliation(s)
- Takuma Murofushi
- Department of Clinical Pharmacology and Genetics, University of Shizuoka, Shizuoka, Japan
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, 431-3192, Japan
| | - Tatsuya Yagi
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, 431-3192, Japan.
| | - Daiki Tsuji
- Department of Clinical Pharmacology and Genetics, University of Shizuoka, Shizuoka, Japan
| | - Daisuke Furushima
- School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
| | - Tomoyuki Fujikura
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Kunihiko Itoh
- Department of Clinical Pharmacology and Genetics, University of Shizuoka, Shizuoka, Japan
| | - Junichi Kawakami
- Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Chuo-Ku, Hamamatsu, 431-3192, Japan
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Ang SP, Chia JE, Valladares C, Patel S, Gewirtz D, Iglesias J. Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis. Biomedicines 2024; 12:1414. [PMID: 39061988 PMCID: PMC11274577 DOI: 10.3390/biomedicines12071414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 06/16/2024] [Accepted: 06/22/2024] [Indexed: 07/28/2024] Open
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are among the most commonly prescribed medications. Recently, PPI use has been linked to the development of chronic kidney disease (CKD) and cardiovascular events. Our study aimed to investigate the relationship between PPI use and the incidence of chronic kidney disease using a systematic review and meta-analysis. METHODS We performed a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until March 2024 for relevant studies. We compared outcomes between patients using PPIs, those not using PPIs, and those using histamine-2 receptor antagonists (H2RAs). Endpoints were pooled using the DerSimonian-and-Laird random-effects model as the hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS Our analysis included twelve studies with a total of 700,125 participants (286,488 on PPIs, 373,848 not on PPIs, and 39,789 on H2RAs), with follow-up periods ranging from three months to 14 years. The current meta-analysis revealed that PPI use is associated with a statistically significant increased risk of incident CKD (HR: 1.26, 95% CI: 1.16-1.38, p < 0.001) compared with non-users. Moreover, the risk of incident CKD is significantly higher in patients with PPI use compared to H2RA use (HR: 1.34, 95% CI: 1.13-1.59, p < 0.001). The results remained unchanged in terms of magnitude and direction after a leave-one-out analysis for both outcomes. CONCLUSIONS Our multifaceted analysis showed that PPI use was associated with a higher incidence of CKD when compared to non-PPI use and H2RA use, respectively. These findings advocate for heightened vigilance and judicious use of long-term PPIs. Further large prospective longitudinal studies are warranted to validate these observations.
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Affiliation(s)
- Song Peng Ang
- Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA; (C.V.); (D.G.)
| | - Jia Ee Chia
- Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA;
| | - Carlos Valladares
- Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA; (C.V.); (D.G.)
| | - Shreya Patel
- Touro College of Osteopathic Medicine, New York, NY 10027, USA;
| | - Daniel Gewirtz
- Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA; (C.V.); (D.G.)
| | - Jose Iglesias
- Department of Medicine, Rutgers Health Community Medical Center, Toms River, NJ 08755, USA; (C.V.); (D.G.)
- Department of Medicine, Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
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Prabhoo RY, Pai UA, Wadhwa A, Pillai BV, D'souza C, Wadhawan M, Bhatnagar M, Prabhoo MR, Shetty S, Seshadri VP, Bhatnagar S, Manchanda SC, Kher V. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepatogastroenterol 2024; 14:99-119. [PMID: 39022200 PMCID: PMC11249898 DOI: 10.5005/jp-journals-10018-1430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 04/22/2024] [Indexed: 07/20/2024] Open
Abstract
The use of acid suppression therapy (AST) is a common approach for managing a wide spectrum of acid peptic disorders. Histamine type 2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the most widely prescribed AST in routine clinical practice. However, an exponential surge in the prescriptions of PPIs, such as Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole in recent years and their associated adverse effects have raised concern about their inappropriate and overuse, both in children and adults. To address these issues, a three-step modified Delphi polling process was employed to establish best practice consensus statements for rationalizing the use of acid suppressants. A multidisciplinary expert panel of 13 health professionals across medical specialties, including gastroenterologists, hepatologists, pediatric gastroenterologists, pediatricians, otolaryngologists, cardiologists, nephrologists, gynecologist and orthopedists actively contributed to this collaborative process of consensus development. The expert panel proposed 21 consensus statements providing best practice points on the general use and safety of acid suppressants based on a comprehensive review of scientific literature and clinical expertise. The panel also collaboratively developed a PPI deprescribing algorithm. Altogether, this consensus paper offers evidence-based recommendations and guidance for the rational use of acid suppressants with a blueprint for deprescribing PPIs. This consensus paper contributes to aiding primary care practitioners in improving patient outcomes and minimizing healthcare costs. Additionally, it enhances patient safety and curtail inappropriate usage. How to cite this article Prabhoo RY, Pai UA, Wadhwa A, et al. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepato-Gastroenterol 2024;14(1):99-119.
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Affiliation(s)
- Ram Y Prabhoo
- Department of Orthopedics, Mukund Hospital, Mumbai, Maharashtra, India
| | - Uday A Pai
- Department of Pediatrics, Sai Kutti Clinic, Mumbai, Maharashtra, India
| | - Arun Wadhwa
- Department of Pediatrics, Arun Wadhwa Clinic, New Delhi, India
| | - Bhanu V Pillai
- Department of Pediatric Gastroenterology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Chris D'souza
- Department of ENT, Holy Family Hospital, Mumbai, Maharashtra, India
| | - Manav Wadhawan
- Department of Hepatology and Liver Transplant, BLK-Max Super Speciality Hospital, Delhi, India
| | - Manish Bhatnagar
- Department of Gastroenterology, Orchid Mediservices, Ahmedabad, Gujarat, India
| | - Meena R Prabhoo
- Department of Gynecology, Mukund Hospital, Mumbai, Maharashtra, India
| | - Sadanand Shetty
- Department of Cardiology, Somaiya Super Specialty Institute, Mumbai, Maharashtra, India
| | | | - Shrish Bhatnagar
- Department of Pediatric Gastroenterology, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | | | - Vijay Kher
- Department of Nephrology and Transplant Medicine, Epitome Kidney and Urology Institute, New Delhi, India
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Parmar MP, Kaleem S, Samuganathan P, Ishfaq L, Anne T, Patel Y, Bollu S, Vempati R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review. Cureus 2023. [DOI: 10.7759/cureus.49883 | pmid: 38174181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2025] Open
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Parmar MP, Kaleem S, Samuganathan P, Ishfaq L, Anne T, Patel Y, Bollu S, Vempati R. Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review. Cureus 2023; 15:e49883. [PMID: 38174181 PMCID: PMC10762285 DOI: 10.7759/cureus.49883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 12/03/2023] [Indexed: 01/05/2024] Open
Abstract
Proton pump inhibitors (PPIs) are widely prescribed medications for the management of various gastrointestinal disorders, primarily gastroesophageal reflux disease (GERD) and peptic ulcers. However, recent concerns have emerged regarding their potential adverse effects on kidney function and their role in the progression of chronic kidney disease (CKD). This systematic review aims to comprehensively analyze the existing literature to assess the impact of PPI use on kidney function and CKD progression. We took information from PubMed, PubMed Central (PMC), and Google Scholar articles from the last 10 years, from 2013 to 2023, and looked for links between PPI use and a number of kidney-related outcomes. These included acute kidney injury, a drop in the estimated glomerular filtration rate (eGFR), and new cases of CKD. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve were taken out and looked at to see if there were any links between PPI use and different kidney-related events, such as acute kidney injury, a drop in the estimated eGFR, and the development of CKD. The review also explores potential mechanisms underlying PPI-induced nephrotoxicity. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve patient care. Further research is warranted to better understand the complex interplay between PPIs, kidney function, and CKD progression.
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Affiliation(s)
- Mihirkumar P Parmar
- Internal Medicine, Gujarat Medical Education and Research Society, Vadnagar, IND
| | - Safa Kaleem
- Internal Medicine, Shadan Institute of Medical Sciences, Hyderabad, IND
| | | | - Lyluma Ishfaq
- Internal Medicine, Government Medical College Srinagar, Srinagar, IND
| | - Tejawi Anne
- Internal Medicine, Gandhi Medical College & Hospital, Secunderabad, IND
| | - Yashaswi Patel
- Internal Medicine, Government Medical College Surat, Surat, IND
| | - Sashank Bollu
- Internal Medicine, Gandhi Medical College, Hyderabad, IND
| | - Roopeessh Vempati
- Internal Medicine, Gandhi Medical College & Hospital, Hyderabad, IND
- Cardiology, Heart and Vascular Institute, Detroit, USA
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Miedziaszczyk M, Idasiak-Piechocka I. Safety analysis of co-administering tacrolimus and omeprazole in renal transplant recipients - A review. Biomed Pharmacother 2023; 166:115149. [PMID: 37619481 DOI: 10.1016/j.biopha.2023.115149] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 07/01/2023] [Accepted: 07/07/2023] [Indexed: 08/26/2023] Open
Abstract
Tacrolimus is a calcineurin inhibitor used to prevent rejection in allogenic solid organ transplant recipients, which is metabolized in the liver with cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5). In turn, proton pump inhibitors (PPIs), such as Omeprazole - a substrate and inhibitor of CYP2C19 and CYP3A4 enzymes - are administered to kidney transplant patients in order to prevent duodenal and gastric ulcer disease, associated with the glucocorticoid treatment. Simultaneous administration of both drugs in renal patients has the potential to trigger drug interactions. In fact, there are several mechanisms which may impact the pharmacokinetics of tacrolimus. Inhibition of the CYP2C19 isoform may suppress the metabolism of omeprazole, subsequently altering its metabolic pathway to be metabolized by the CYP3A4 enzyme in order to maintain adequate biotransformation. Therefore, the competition for CYP3A4 may affect the metabolism of tacrolimus and result in its increased plasma concentrations, as well as in adverse reactions. Another mechanism has been related to the genetic polymorphism of the CYP2C19 isoform. Since all these interactions may lead to dysfunctions of the transplanted kidney, it seems significant to eliminate their consequences, for instance via the administration of drugs which are neither substrates, nor inhibitors of the CYP3A4 enzyme. Finally, the nephrotoxic effect of omeprazole should also be accounted for. Bearing in mind the aforementioned observations, the aim of the presented paper was to review the available studies addressing the effect of omeprazole on the pharmacokinetics of tacrolimus.
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Affiliation(s)
- Miłosz Miedziaszczyk
- Department of Nephrology, Transplantology and Internal Medicine, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland.
| | - Ilona Idasiak-Piechocka
- Department of Nephrology, Transplantology and Internal Medicine, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355 Poznan, Poland
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Barraquer Comes A, Roy Millán P. Proton Pump Inhibitor Deprescription Prospective Study in Patients Without Indication: Are There Differences in Proportion of Restarts According to Withdrawal Strategy? J Pharm Technol 2023; 39:224-230. [PMID: 37745729 PMCID: PMC10515970 DOI: 10.1177/87551225231195216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023] Open
Abstract
Background: The increasing utilization of proton pump inhibitors (PPIs) in patients without clear medical indications has raised concerns regarding potential risks, highlighting the importance of deprescription. However, comparative analyses of withdrawal strategies (abrupt vs gradual) in this context remain scarce or of low quality. Aim: This study aimed to evaluate the success rate of deprescribing PPIs in hospitalized patients without a documented indication and compare the proportion of treatment restarts based on withdrawal strategy. Method: An uncontrolled, open-label prospective observational study was conducted on patients receiving PPI treatment during hospital admission between May 2017 and July 2018. Deprescription was recommended for patients without a clear indication. Follow-up continued until discharge, with monitoring for rebound symptoms. The percentage of restarts based on the withdrawal strategy was compared using the chi-square test. Results: A total of 402 patients were reviewed, among whom 27% lacked a medical indication (mean age > 60 years, polymedicated), while 70% were prescribed PPIs electronically. Deprescription was performed in 49% of patients, with 64% undergoing abrupt withdrawal. Rebound symptoms led to treatment restart in 15% of cases. However, the chi-square test revealed no significant differences in restart proportions between the abrupt and gradual withdrawal groups (P = 0.365). Conclusion: Deprescribing PPIs is deemed safe, particularly for polymedicated geriatric patients, as it leads to a low percentage of restarts regardless of the chosen withdrawal strategy. However, the high percentage of PPI prescription without a clear indication underlines the need for periodic reassessment to avoid unnecessary risks and overuse.
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Affiliation(s)
- Anna Barraquer Comes
- Pharmaceutical specialist in hospital Pharmacy, Department manager, Hospital Mare de Déu de la Mercè, Barcelona, Spain
| | - Pedro Roy Millán
- Medical director, Hospital Mare de Déu de la Mercè, Barcelona, Spain
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Dos Santos AS, de Menezes ST, Silva IR, Oliveira WN, Pereira ML, Mill JG, Barreto SM, Figueiredo RC. Kidney function decline associated with proton pump inhibitors: results from the ELSA-Brasil cohort. BMC Nephrol 2023; 24:285. [PMID: 37770872 PMCID: PMC10538238 DOI: 10.1186/s12882-023-03300-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 08/16/2023] [Indexed: 09/30/2023] Open
Abstract
OBJECTIVE Investigate the longitudinal association of use and time of use of proton pump inhibitors (PPI) with incidence of chronic kidney disease (CKD) and kidney function change. METHODS Prospective study with 13,909 participants from baseline (2008-2010) and second wave (2012-2014) of the ELSA-Brasil (mean interval between visits = 3.9 years (1.7-6.0)). Participants answered about use and time use of the PPI in the two weeks prior the interview. Renal function was assessed by glomerular filtration rate estimated by the Collaboration Equation for the Epidemiology of Chronic Kidney Disease. Values below 60ml/min/1.73 m² in wave 2 were considered incident CKD. Associations between PPI use and time of use at baseline and incident CKD and decline in renal function were estimated, respectively, by logistic regression and linear models with mixed effects, after adjusting for confounders. RESULTS After adjustments, PPI users for more than six months had an increased risk of CKD compared to non-users. Compared to non-users, users PPIs for up to six months and above six months had greater decline in kidney function over time. CONCLUSION This cohort of adults and elderly, after a mean interval of 3.9 years, PPI use and initial duration were associated with kidney function change between visits.
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Affiliation(s)
- Andrêza Soares Dos Santos
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - Sara Teles de Menezes
- Longitudinal Study of Adult Health - ELSA-Brasil, Medical School & Clinical Hospital/EBSERH, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Isabella Ribeiro Silva
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - William Neves Oliveira
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - Mariana Linhares Pereira
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil
| | - José Geraldo Mill
- Department of Physiological Sciences & University Hospital, Universidade Federal do Espírito Santo, Vitória, Brazil
| | - Sandhi Maria Barreto
- Medical School & Clinical Hospital/EBSERH, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Roberta Carvalho Figueiredo
- Postgraduate Program in Health Sciences, Universidade Federal de São João del-Rei, Sebastião Gonçalves Coelho Street, 400 - Chanadour, Divinópolis, 35501-296, MG, Brazil.
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12
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Zhang Y, Ghahramani N, Razjouyan H, Ba DM, Chinchilli VM. The association between proton pump inhibitor use and risk of post-hospitalization acute kidney injury: a multicenter prospective matched cohort study. BMC Nephrol 2023; 24:150. [PMID: 37237361 DOI: 10.1186/s12882-023-03211-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 05/22/2023] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Proton Pump Inhibitors (PPI) are among the most commonly used drugs to treat acid-related gastrointestinal disorders in the USA. Although PPI use has been linked to acute interstitial nephritis, the side effects of post-hospitalization acute kidney injury (AKI) and the progression of kidney disease still are controversial. We conducted a matched cohort study to examine the associations between PPI use and the side effects, especially in post-hospitalization AKI. METHODS We investigated 340 participants from the multicenter, prospective, matched-cohort ASSESS-AKI study, which enrolled participants from December 2009 to February 2015. After the baseline index hospitalization, follow-up visits were conducted every six months, and included a collection of self-reported PPI use by participants. Post-hospitalization AKI was defined as the percentage increase from the nadir to peak inpatient SCr value was ≥ 50% and/or absolute increase ≥ 0.3 mg/dL in peak inpatient serum creatinine compared with baseline outpatient serum creatinine. We applied a zero-inflated negative binomial regression model to test the relationship between PPI use and post-hospitalization AKI. Stratified Cox proportional hazards regression models also were conducted to examine the association between PPI use and the risk of progression of kidney disease. RESULTS After controlling for demographic variables, baseline co-morbidities and drug use histories, there was no statistically significant association between PPI use and risk of post-hospitalization AKI (risk ratio [RR], 0.91; 95% CI, 0.38 to 1.45). Stratified by AKI status at baseline, no significant relationships were confirmed between PPI use and the risk of recurrent AKI (RR, 0.85; 95% CI, 0.11 to 1.56) or incidence of AKI (RR, 1.01; 95% CI, 0.27 to 1.76). Similar non-significant results also were observed in the association between PPI use and the risk of progression of kidney diseases (Hazard Ratio [HR], 1.49; 95% CI, 0.51 to 4.36). CONCLUSION PPI use after the index hospitalization was not a significant risk factor for post-hospitalization AKI and progression of kidney diseases, regardless of the AKI status of participants at baseline.
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Affiliation(s)
- Yue Zhang
- Department of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA, 17033, USA.
| | - Nasrollah Ghahramani
- Department of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA, 17033, USA
- Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Hadie Razjouyan
- Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Djibril M Ba
- Department of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA, 17033, USA
| | - Vernon M Chinchilli
- Department of Public Health Sciences, Penn State College of Medicine, 90 Hope Drive, Hershey, PA, 17033, USA
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Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J 2023; 59:115-127. [PMID: 37303818 PMCID: PMC10248387 DOI: 10.4068/cmj.2023.59.2.115] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/03/2023] [Accepted: 05/04/2023] [Indexed: 06/13/2023] Open
Abstract
Proton Pump Inhibitors are used widely to manage many gastric acid-related conditions such as gastroesophageal disease, gastritis, esophagitis, Barrett's esophagus, Zollinger-Ellison syndrome, peptic ulcer disease, nonsteroidal anti-inflammatory drug-associated ulcers, and Helicobacter pylori eradication, around the globe. This review article focuses on adverse effects associated with the long-term use of proton pump inhibitors. Various observational studies, clinical trials, and meta-analyses have established the adverse effects associated with the long-term use of proton pump inhibitors including renal disorders (acute interstitial nephritis, acute kidney injury, chronic kidney disease, and end-stage renal disease), cardiovascular risks (major adverse cardiovascular events, myocardial infarction, stent thrombosis, and stroke), fractures, infections (Clostridium difficile infection, community-acquired pneumonia, and Coronavirus disease 2019), micronutrient deficiencies (hypomagnesemia, anemia, vitamin B12 deficiency, hypocalcemia, hypokalemia), hypergastrinemia, cancers (gastric cancer, pancreatic cancer, colorectal cancer, hepatic cancer), hepatic encephalopathy, and dementia. Clinicians including prescribers and pharmacists should be aware of the adverse effects of taking proton pump inhibitors for an extended period of time. In addition, the patients taking proton pump inhibitors for long-term should be monitored for the listed adverse effects. The American Gastroenterological association recommends a few non-pharmacological measures and the use of histamine 2 blockers to lessen gastrointestinal symptoms of gastroesophageal reflex disease and the utilization of proton pump inhibitors treatment if there is a definitive indication. Additionally, the American Gastroenterological association's Best Practice Advice statements emphasize deprescribing when there is no clear indication for proton pump inhibitors therapy.
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14
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Kou N, Shimoda T, Ito H. Proton Pump Inhibitors and Acute Kidney Injury After Cardiac Surgery. Mayo Clin Proc 2023; 98:803. [PMID: 37137648 DOI: 10.1016/j.mayocp.2023.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 03/21/2023] [Indexed: 05/05/2023]
Affiliation(s)
- Noriaki Kou
- College of Medicine, School of Medicine and Health Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Tomonari Shimoda
- College of Medicine, School of Medicine and Health Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Hiroshi Ito
- Division of General Internal Medicine, Department of Internal Medicine, Tokyo Medical University Ibaraki Medical Center, Ibaraki, Japan
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15
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Koh HB, Park JT. In Reply-Proton Pump Inhibitors and Acute Kidney Injury After Cardiac Surgery. Mayo Clin Proc 2023; 98:803-804. [PMID: 37137647 DOI: 10.1016/j.mayocp.2023.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 03/21/2023] [Indexed: 05/05/2023]
Affiliation(s)
- Hee Byung Koh
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea; International Saint Mary's Hospital, Catholic Kwandong University, Seo-gu, Incheon, South Korea
| | - Jung Tak Park
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, Republic of Korea
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16
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Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies. J Clin Med 2023; 12:2262. [PMID: 36983271 PMCID: PMC10052387 DOI: 10.3390/jcm12062262] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/11/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Previous epidemiological studies have raised the concern that the use of proton pump inhibitors (PPIs) is associated with an increased risk of kidney diseases. To date, no comprehensive meta-analysis has been conducted to assess the association between PPIs and the risk of chronic kidney disease (CKD). Therefore, we conducted a systematic review and meta-analysis to address the association between PPIs and CKD. The primary search was conducted in the most popular databases, such as PubMed, Scopus, and Web of Science. All observational studies evaluated the risk of CKD among PPI users, and non-users were considered for inclusion. Two reviewers conducted data extraction and assessed the risk of bias. Random-effect models were used to calculate pooled effect sizes. A total of 6,829,905 participants from 10 observational studies were included. Compared with non-PPI use, PPI use was significantly associated with an increased risk of CKD (RR 1.72, 95% CI: 1.02-2.87, p = 0.03). This updated meta-analysis showed that PPI was significantly associated with an increased risk of CKD. Association was observed in the same among moderate-quality studies. Until further randomized control trials (RCTs) and biological studies confirm these results, PPI therapy should not stop patients with gastroesophageal reflux disease (GERD). However, caution should be used when prescribing to patients with high-risk kidney disease.
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Affiliation(s)
- Chieh-Chen Wu
- Department of Healthcare Information and Management, School of Health Technology, Ming Chuan University, Taoyuan 33300, Taiwan
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan
| | - Mao-Hung Liao
- Superintendent Office, Yonghe Cardinal Tien Hospital, New Taipei City 23148, Taiwan
| | - Woon-Man Kung
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan
- Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
| | - Yao-Chin Wang
- Department of Emergency, Min-Sheng General Hospital, Taoyuan 33044, Taiwan
- Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan
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Pannoi T, Promchai C, Apiromruck P, Wongpraphairot S, Yang CC, Pan WC. Estimates of Chronic Kidney Diseases Associated with Proton-Pump Inhibitors Using a Retrospective Hospital-Based Cohort in Thailand. Int J Nephrol Renovasc Dis 2022; 15:371-381. [PMID: 36530347 PMCID: PMC9753254 DOI: 10.2147/ijnrd.s389238] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Accepted: 12/01/2022] [Indexed: 02/07/2024] Open
Abstract
PURPOSE Potential adverse outcomes of Proton pump inhibitors (PPIs) have increasingly been reported. The potential risks to PPIs include hypomagnesemia and chronic kidney disease (CKD). Unlike a real-world electronic medical record (RW-EMR) with active-comparator design, claim databases and special population cohort with non-user design, using in previous studies, resulted in a wide range of strength of association with indication bias. This study aimed to measure the total effect of association between PPIs use and CKD incidence using Thai RW-EMR. PATIENTS AND METHODS A retrospective hospital-based cohort was applied into this study. Electronic medical records and administrative data of out- and inpatient were retrieved from October 1st, 2010 to September 30th, 2017. On-treatment with grace period as well as propensity score matching was used in data analysis. Cox proportional hazard models were applied to evaluate the PPIs-CKD association. RESULTS Of all 63,595 participants, a total of 59,477 new PPIs and 4118 Histamine 2-receptor antagonist (H2RA) users were eligible for follow-up. As compared with H2RA, the PPI users were non-elderly and more likely being female. The association of PPIs with CKD was statistically significant (adjusted hazard ratio [HR] = 3.753, 95% CI = 2.385-5.905). The HR were not statistically different by concomitant use PPIs with NSAIDs and by medication possession ratio levels. CONCLUSION The association between PPIs and CKD incidence was statistically significant in this hospital-based cohort. However, self-treatment with over-the-counter PPIs, as well as, smoking, drinking alcohol and body mass index could not be fully retrieved, affecting the estimation of treatment effect.
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Affiliation(s)
- Tanavij Pannoi
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhon-Si-Thammarat, Thailand
| | - Chissanupong Promchai
- Department of Pharmacy, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Penjamaporn Apiromruck
- Department of Pharmacy, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Suwikran Wongpraphairot
- Department of Nephrology Unit, Songklanagarind Hospital, Prince of Songkla University, Songkla, Thailand
| | - Chen-Chang Yang
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Department of Occupational Medicine and Clinical Toxicology, Taipei Veteran General Hospital, Taipei City, Taiwan
| | - Wen-Chi Pan
- International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei City, Taiwan
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei City, Taiwan
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18
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Dewan T, Turner J, Lethebe BC, Johnson DW. Gastro-oesophageal reflux disease in children with neurological impairment: a retrospective cohort study. BMJ Paediatr Open 2022; 6:10.1136/bmjpo-2022-001577. [PMID: 36645746 PMCID: PMC9490596 DOI: 10.1136/bmjpo-2022-001577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 09/06/2022] [Indexed: 02/02/2023] Open
Abstract
OBJECTIVES To determine the incidence and prevalence of gastro-oesophageal reflux disease (GERD) diagnosis and treatment in children with neurological impairment (NI) along with relationship to key variables. DESIGN This is a population-based retrospective cohort study. SETTING This study takes place in Alberta, Canada. PATIENTS Children with NI were identified by hospital-based International Classification of Diseases (ICD) codes from 2006 to 2018. MAIN OUTCOME MEASURES Incidence and prevalence of a GERD diagnosis identified by: (1) hospital-based ICD-10 codes; (2) specialist claims; (3) dispensation of acid-suppressing medication (ASM). Age, gender, complex chronic conditions (CCC) and technology assistance were covariates. RESULTS Among 10 309 children with NI, 2772 (26.9%) met the GERD definition. The unadjusted incidence rate was 52.1 per 1000 person-years (50.2-54.1). Increasing numbers of CCCs were associated with a higher risk of GERD. The HR for GERD associated with a gastrostomy tube was 4.56 (95% CI 4.15 to 5.00). Overall, 2486 (24.1%) of the children were treated with ASMs of which 1535 (61.7%) met no other GERD criteria. The incidence rate was 16.9 dispensations per year (95% CI 16.73 to 17.07). The prevalence of gastrojejunostomy tubes was 1.1% (n=121), surgical jejunostomy tubes was 0.7% (n=79) and fundoplication was 3.4% (n=351). CONCLUSIONS The incidence of GERD in children with NI greatly exceeds that of the general paediatric population. Similarly, incidence rate of medication dispensations was closer to the rates seen in adults particularly in children with multiple CCCs and gastrostomy tubes. Further research is needed to determine the appropriate use of ASMs balancing the potential for adverse effects in this population.
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Affiliation(s)
- Tammie Dewan
- Pediatrics, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
| | - Justine Turner
- Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | | | - David W Johnson
- Pediatrics, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
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Wei X, Yu J, Xu Z, Wang C, Wu Y. Incidence, Pathogenesis, and Management of Proton Pump Inhibitor-Induced Nephrotoxicity. Drug Saf 2022; 45:703-712. [PMID: 35641849 DOI: 10.1007/s40264-022-01181-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/26/2022] [Indexed: 11/25/2022]
Abstract
Proton pump inhibitors are widely used in the treatment of various acid-related diseases and are among the most commonly used drugs. Studies estimate that 25-70% of proton pump inhibitors are prescribed for inappropriate treatments, doses, and indications, where the benefits of proton pump inhibitor use may be less than the risk of adverse drug reactions for many patients. Acute interstitial nephritis is an immune-mediated atypical kidney injury in the long-term use of proton pump inhibitors that causes problems for clinicians and patients. In this review, we summarize the current knowledge of proton pump inhibitors inducing acute interstitial nephritis, chronic kidney disease, and even end-stage renal disease in terms of incidence, pathogenesis, factors, clinical features, and diagnosis. We discuss how these factors change under conditions of acute interstitial nephritis, chronic kidney disease, and end-stage renal disease. The purpose of this review is to assess the current evidence to help clinicians and patients interpret the potential causal relationship between proton pump inhibitor intake and nephrotoxicity. This prompts clinicians to consider the appropriate dose and duration of proton pump inhibitor therapy to avoid inappropriate use.
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Affiliation(s)
- Xiao Wei
- Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China.,Blood Purification Center, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Jun Yu
- Institute of Clinical Pharmacology, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Zhengkun Xu
- Institute of Clinical Pharmacology, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Chun Wang
- Institute of Clinical Pharmacology, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China.
| | - Yonggui Wu
- Department of Nephrology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China.
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20
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Kulkarni S, Raj J, Pinto R, Tomy S. Diabetic nephropathy and proton pump inhibitors – Pilot case-control study. Indian J Nephrol 2022; 32:127-131. [PMID: 35603105 PMCID: PMC9121724 DOI: 10.4103/ijn.ijn_397_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 10/10/2020] [Accepted: 06/01/2021] [Indexed: 11/04/2022] Open
Abstract
Introduction: Methods: Results: Conclusion:
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21
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Cholin L, Ashour T, Mehdi A, Taliercio JJ, Daou R, Arrigain S, Schold JD, Thomas G, Nally J, Nakhoul NL, Nakhoul GN. Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression. BMC Nephrol 2021; 22:264. [PMID: 34266395 PMCID: PMC8281649 DOI: 10.1186/s12882-021-02449-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/31/2021] [Indexed: 11/12/2022] Open
Abstract
Background The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk. Results 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71). Conclusions Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02449-0.
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Affiliation(s)
| | | | - Ali Mehdi
- Cleveland Clinic, Cleveland, OH, USA
| | | | - Remy Daou
- Saint-Joseph University, Beirut, Lebanon
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Giusti S, Lin Y, Sogbetun F, Nakhoul N, Liu S, Shi L, Batuman V. The Effect of Proton Pump Inhibitor Use on the Course of Kidney Function in Patients with Chronic Kidney Disease Stages G3a to G4. Am J Med Sci 2021; 362:453-461. [PMID: 34033809 DOI: 10.1016/j.amjms.2021.05.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 04/07/2021] [Accepted: 05/20/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are widely used and implicated in the progression of chronic kidney disease (CKD). We evaluated the relation between chronic PPI use in veterans with CKD G3a to G4 and the rate of decline in renal function. METHODS We accessed the Veteran Affairs Informatics and Computing Infrastructure national database to evaluate the relation between chronic PPI use and rate of decline in renal function in veterans with CKD (eGFR <60 ml/min1.73 m2). We applied Propensity Score Matching to match the PPI group and the no-PPI control group on age, sex, race, and Charlson Comorbidity Index. The final sample included 1406 patients (age: 62.07±7.82, 62.02% Caucasian) in the PPI cohort with a median 4.7 years follow-up and 1425 patients (age: 65.45±6.58, 71.16% Caucasian) in the control cohort with a median 3.9 years follow-up. Kaplan-Meier curve and Cox regression were performed to analyze the associations of PPI use with dialysis, all-cause mortality, metabolic acidosis, and CKD progression. RESULTS The PPI group had a significantly increased risk of CKD progression, dialysis and all-cause mortality (aHR, 1.83; 95% CI, 1.53 to 2.19; aHR, 1.84; 95% CI, 1.26 to 2.67; and aHR, 1.34; 95% CI, 1.08 to 1.65, respectively). The PPI cohort also had a trend for development of metabolic acidosis (aHR, 1.34; 95% CI, 0.998 to 1.80), although the difference was not statistically significant. CONCLUSIONS The data suggest that chronic PPI use accelerates progression of kidney disease and is associated with increased mortality in CKD patients.
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Affiliation(s)
- Sixto Giusti
- Tulane University School of Medicine, Deming Department of Medicine, Section of Nephrology, New Orleans, Louisiana; Southeast Louisiana Veterans Health Care System, Medicine Service, Section of Nephrology, New Orleans, Louisiana.
| | - Yilu Lin
- Tulane University School of Public Health Department of Global Health Management and Policy (GHMP) Tulane University School of Public Health and Tropical Medicine (TUSPHTM), New Orleans, Louisiana
| | - Folarin Sogbetun
- Tulane University School of Medicine, Deming Department of Medicine, Section of Nephrology, New Orleans, Louisiana
| | - Nazih Nakhoul
- Tulane University School of Medicine, Deming Department of Medicine, Section of Nephrology, New Orleans, Louisiana
| | - Shuqian Liu
- Tulane University School of Public Health Department of Global Health Management and Policy (GHMP) Tulane University School of Public Health and Tropical Medicine (TUSPHTM), New Orleans, Louisiana
| | - Lizheng Shi
- Tulane University School of Public Health Department of Global Health Management and Policy (GHMP) Tulane University School of Public Health and Tropical Medicine (TUSPHTM), New Orleans, Louisiana
| | - Vecihi Batuman
- Tulane University School of Medicine, Deming Department of Medicine, Section of Nephrology, New Orleans, Louisiana; Southeast Louisiana Veterans Health Care System, Medicine Service, Section of Nephrology, New Orleans, Louisiana
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Wakabayashi T, Hosohata K, Oyama S, Inada A, Niinomi I, Kambara H, Iida T, Hasebe K, Matsuoka H, Uchida M, Kumagai E. Association between a low dose of proton pump inhibitors and kidney function decline in elderly hypertensive patients: a retrospective observational study. J Int Med Res 2021; 49:3000605211006653. [PMID: 33845606 PMCID: PMC8047853 DOI: 10.1177/03000605211006653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Objectives Proton pump inhibitors (PPIs) are widely used for acid suppression therapy. Recently, PPI use was reported to be associated with chronic kidney disease (CKD); however, whether a low dose of PPIs is associated with CKD remains unknown. Methods This retrospective observational study included hypertensive patients who visited Kenwakai Hospital between 2017 and 2019. Renal parameters, such as the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), were extracted from medical records and compared between three years before treatment and the baseline. PPI use was assessed as cumulative exposure for three years. Results The study population included 152 patients (57.9% men; mean age, 74.5 years). Of those, 35.5% were PPI users (low dose, 17.1%; high dose, 18.4%). A significant decrease in eGFR and an increase in Scr were observed between three years before treatment and the baseline in the high-dose PPI group but not the non-use or low-dose PPI groups. Conclusions Our results suggest that a low dose of PPIs may be safe in clinical settings, but further prospective studies are needed to clarify our findings.
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Affiliation(s)
- Tomohito Wakabayashi
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Keiko Hosohata
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Saki Oyama
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Ayaka Inada
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Iku Niinomi
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Hiroko Kambara
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Tatsuya Iida
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Keiko Hasebe
- Department of Nephrology, Kenwakai Hospital, Nagano, Japan
| | | | - Mayako Uchida
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Osaka, Japan
| | - Etsuko Kumagai
- Department of Nephrology, Kenwakai Hospital, Nagano, Japan
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Schiffl H, Al-Nemnem E, Lang SM. Proton-pump inhibitors and chronic kidney disease: Hidden consequences of an inappropriate drug use? SAUDI JOURNAL OF KIDNEY DISEASES AND TRANSPLANTATION 2021; 31:312-319. [PMID: 32394903 DOI: 10.4103/1319-2442.284005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Proton-pump inhibitors (PPIs) are the most effective therapy for gastric acid- related diseases. They are generally well tolerated with rare, often self-limiting adverse reactions. On the other hand, there is growing concern regarding the increased public access and inappropriate PPI use. This review aims to give a critical appraisal of current literature and to analyze a possible relationship between renal disorders and PPI use. A plethora of observational pharmacoepidemiological studies link PPI therapy to the development of acute interstitial nephritis (AIN). Most of these studies show a higher risk for acute kidney injury, de novo chronic kidney disease, and end-stage renal disease. However, current evidence is inadequate to establish a causal relationship between PPI use and many of the proposed renal syndromes. Residual confounding and bias related to study design and the over extrapolation of quantitatively small treatment effects contributed to the unnecessary controversy about PPI safety. Undoubtedly, PPI use may rarely induce AIN. Given the worldwide use of PPIs, the number of patients with biopsy- proven AIN is extremely small. However, more research is required to explore the underlying pathophysiological mechanisms and possible differences between commercially available PPIs regarding adverse renal effects. Till then, the PPIs should be used in the lowest effective dose, and inappropriate use should be avoided.
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Affiliation(s)
- Helmut Schiffl
- Department of Internal Medicine IV, University Hospital Munich, Munich, Germany
| | - Emad Al-Nemnem
- Department of Internal Medicine 2, SRH Wald-Klinikum Gera, Gera, Germany
| | - Susanne M Lang
- Department of Internal Medicine 2, SRH Wald-Klinikum Gera, Gera, Germany
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Vengrus CS, Delfino VD, Bignardi PR. Proton pump inhibitors use and risk of chronic kidney disease and end-stage renal disease. Minerva Urol Nephrol 2021; 73:462-470. [PMID: 33769018 DOI: 10.23736/s2724-6051.21.04116-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
INTRODUCTION A possible association between long-term proton pump inhibitors (PPI) use and chronic kidney disease (CKD) has been recently described. Due to the potential health risk of this association, in the absence of proper clinical trials, we have decided to carry out a systematic review followed by meta-analysis. EVIDENCE ACQUISITION PubMed, Cochrane Library, and Lilacs databases were searched. Studies that reported an association between PPI use and CKD or End-stage Renal Disease (ESRD) published until December 23, 2019, were included. All selected studies present high quality according to the New-Castle-Ottawa. The risk ratio (RR) and confidence interval (CI) were pooled using a random-effects model in CKD outcome analysis and fixed effects model for ESRD. A total of 10 observational studies were selected. EVIDENCE SYNTHESIS Compared to patients who did not use PPI, the RR for CKD associated with PPI use was 1.35 (95% CI 1.15-1.56) with P<0.001, and the RR for ESRD associated with PPI use was 1.49 (95% CI 1.41-1.56) with P<0.001. CONCLUSIONS This study indicates the presence of a significant association between PPI use and an increased risk of CKD and ESRD and reiterates the need for the medical prescription of this class of drugs to be made following the guidelines of the FDA.
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Affiliation(s)
- Carolina S Vengrus
- School of Medicine, Pontifical Catholic University of Paraná, Londrina, Brazil
| | - Vinícius D Delfino
- School of Medicine, Pontifical Catholic University of Paraná, Londrina, Brazil.,Universidade Estadual de Londrina, Londrina, Brazil
| | - Paulo R Bignardi
- School of Medicine, Pontifical Catholic University of Paraná, Londrina, Brazil -
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Dharmarajan TS. The Use and Misuse of Proton Pump Inhibitors: An Opportunity for Deprescribing. J Am Med Dir Assoc 2020; 22:15-22. [PMID: 33321078 DOI: 10.1016/j.jamda.2020.09.046] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 08/26/2020] [Accepted: 09/06/2020] [Indexed: 02/07/2023]
Abstract
Proton pump inhibitors (PPIs) are proven medications of choice for gastroesophageal reflux disease (GERD), acid-related disorders, erosive esophagitis, Barrett esophagus, prevention of gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs, eosinophilic esophagitis, peptic ulcer disease, stress ulcer prophylaxis in critically ill patients, and other indications. Best practice guidelines from several sources on the appropriate indications and duration of PPI therapy have been summarized for easy assimilation. Individualized decision with regard to PPI use is illustrated by case vignettes; best approaches are provided. The significant increase in use of PPIs for ill-defined indications over the years, associated adverse outcomes with long-term use, and consequent increase in health care costs have drawn much attention. Adverse outcomes due to PPI therapy may be categorized as unrelated or related to gastric acid inhibition. Examples of outcomes unrelated to acid inhibition include allergic reactions, acute interstitial nephritis, chronic kidney disease, poor cardiovascular outcomes, dementia, and drug interactions; consequences of acid inhibition include gastrointestinal infections, pneumonia, nutrient deficiencies, fractures, spontaneous bacterial peritonitis, and small intestinal bacterial overgrowth. Provider awareness regarding best practice guidelines on PPI use and imparting pertinent education to patients may be the rational approach to safe and effective PPI therapy. In individuals in whom the drug is not indicated, efforts at deprescribing the PPI may be attempted following discussion with the patient. Approaches include stopping the drug, reducing the dose or using "on-demand" therapy after completing the course of treatment for the specific indication. Barriers to successful deprescribing exist. Follow-up is recommended for recurrence of manifestations; in the event of recurrence, the PPI may need to be re-instituted. PPIs are valuable, irreplaceable drugs in the prevention and treatment of certain disorders for specific durations of time. Evidence nevertheless suggests that excessive and inappropriately prolonged use of PPIs is associated with a broad range of adverse effects. Education of provider and patient, stewardship, and motivation are key to appropriate use of PPIs for the right indications. Key implications for practice are offered.
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Affiliation(s)
- Thiruvinvamalai S Dharmarajan
- Department of Medicine, Geriatric Medicine, Geriatric Medicine Fellowship Program, Montefiore Medical Center, Wakefield Campus, Bronx, NY, USA; Albert Einstein College of Medicine, Bronx, NY, USA.
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Liu Y, Zhu X, Li R, Zhang J, Zhang F. Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study. BMJ Open 2020; 10:e040473. [PMID: 33243802 PMCID: PMC7692833 DOI: 10.1136/bmjopen-2020-040473] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVES This study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review of electronic medical records in a single-centred hospital. DESIGN All patients admitted to the outpatient department of Jinshan Hospital, Fudan University, Shanghai, between 1 January 2018 and 31 December 2018 were evaluated. Individuals aged 18 years or above and with at least one dispensing for PPIs were identified as PPI users. New PPI users were defined as a subject who did not receive any dispensing for PPIs in the year prior to the index date. Baseline characteristics of PPI users and their therapies were described by treatment indication, economic indicators and co-prescription, overall and separately. SETTING The prescription database was retrieved from the hospital information system of Jinshan Hospital, Fudan University. RESULTS Among 18 435 identified PPI users in 2018, 14 219 patients (aged 18 years or above) who had at least one dispensing PPIs were new users (77%), and among them, men accounted for 47%. The mean treatment duration was 23 days. Omeprazole was the most commonly prescribed drug. PPIs are inappropriately prescribed in 50% (13 589/25 850) of prescriptions. Prescription appropriateness analysis indicated that the unapproved indications for PPI new users accounted for 47%; among them, the proportion of gastritis diagnosis was 34%. The proportion of PPI new users with co-prescription of glucocorticosteroids (GCs) who have risk factors accounted for 24% and lower than other co-prescription. A majority of PPI users (73%) reported high-dose PPI prescription. The defined daily dose of oral pantoprazole was the highest, and injectable omeprazole had the highest defined daily cost. In contrast, only the drug utilisation index value of oral esomeprazole was less than 1.0. CONCLUSION The results indicate the challenge of PPI use was accompanied by unapproved indications, frequent inappropriate co-prescription with GCs and excessive dosages. Efforts should be paid to promote rational use and ensure the choice of suitable PPI therapy in the future.
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Affiliation(s)
- Yujuan Liu
- Clinical Pharmacy Department, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Xian Zhu
- Emergency Department, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Rongxin Li
- Emergency Department, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Jun Zhang
- Clinical Pharmacy Department, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
| | - Feng Zhang
- Emergency Department, Jinshan Hospital Affiliated to Fudan University, Shanghai, China
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Abstract
Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett's esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of Helicobacter pylori. Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
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Affiliation(s)
- David A Katzka
- Mayo Clinic, Division of Gastroenterology and Hepatology, Rochester, MN, USA
| | - Peter J Kahrilas
- Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL USA
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January SE, Progar K, Nesselhauf NM, Hagopian JC, Malone AF. Choice of Acid Suppressant Therapy and Long-Term Graft Outcomes After Kidney Transplantation. Pharmacotherapy 2020; 40:1082-1088. [PMID: 33037663 DOI: 10.1002/phar.2470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
STUDY OBJECTIVE The purpose of this study was to comprehensively evaluate the long-term adverse effects of proton pump inhibitors (PPIs) compared with histamine-2 receptor antagonists (H2RAs) in kidney transplant recipients. METHODS This retrospective cohort compared 582 patients treated with PPI with 705 patients treated with H2RA and evaluated adverse effects throughout their course of acid suppressant therapy to a maximum of nine years posttransplant. The primary outcome of interest was renal function at 1 year posttransplant; secondary outcomes included renal function at 30 days, 3, 5, and 9 years posttransplant as well as rejection, electrolyte and laboratory abnormalities, osteoporosis, pneumonia, and Clostridium difficile infections. RESULTS Renal function did not significantly differ at any timepoint posttransplant. Rejection rates and Clostridium difficile infections were similar between groups; osteoporosis and pneumonia rates were numerically higher in the PPI treated arm but did not reach statistical significance. Proton pump inhibitor (PPI) treated patients were more likely to experience hypomagnesemia requiring supplementation. High dose PPI treated patients had significantly higher rates of pneumonia and osteoporosis compared with H2RA treated patients. Patients were maintained on PPI therapy for an average of 5 years and H2RA therapy for 3 years posttransplant, the majority without a clear indication for therapy. CONCLUSIONS There was no difference in renal function, rejection, or graft loss between PPI and H2RA treated patients. The majority of patients were maintained on PPI therapy for several years posttransplant without a clear indication; critical evaluation of ongoing need for acid suppressant therapy in the posttransplant course should be an area of future focus.
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Affiliation(s)
- Spenser E January
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, Missouri, USA
| | - Kristin Progar
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, Missouri, USA
| | | | | | - Andrew F Malone
- Division of Nephrology, Washington University Physicians, Saint Louis, Missouri, USA
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Wu J, Pu Y. Air pollution, general government public-health expenditures and income inequality: Empirical analysis based on the spatial Durbin model. PLoS One 2020; 15:e0240053. [PMID: 33002068 PMCID: PMC7529191 DOI: 10.1371/journal.pone.0240053] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 09/17/2020] [Indexed: 11/18/2022] Open
Abstract
Environmental pollution and income inequality are important issues related to sustainable economic and social development. Air pollution affects residents' physical health, and income inequality affects social stability and economic development. No scholar has yet confirmed the causal impact of air pollution on income inequality; therefore, this study is an important extension of the environmental Kuznets curve theory. This article examines the impact using balanced panel data from 156 countries (2004-2017) and applies the spatial Durbin model to analyze the mechanism of air pollution's impact on income inequality from the perspective of public health. The results prove the following. First, increasing air pollution does increase income inequality. Second, the spatial spillover effect of air pollution constitutes a relatively important part of the total effect of air pollution on income inequality compared with the direct effect. Third, general government public-health expenditures are an important transmission channel by which air pollution affects income inequality. The conclusions of the research have some important policy implications for environmental governance and income distribution policies at the national as well as supranational level.
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Affiliation(s)
- Jianli Wu
- Institute of Chinese Financial Studies, Southwestern University of Finance and Economics, Chengdu, Sichuan, China
| | - Yue Pu
- School of International Business, Southwestern University of Finance and Economics, Chengdu, Sichuan, China
- * E-mail:
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Gerstman BB. Proton pump inhibitors and chronic kidney disease: Reevaluating the evidence from a randomized controlled trial. Pharmacoepidemiol Drug Saf 2020; 30:4-8. [PMID: 32909330 DOI: 10.1002/pds.5101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/01/2020] [Accepted: 07/27/2020] [Indexed: 12/21/2022]
Affiliation(s)
- B Burt Gerstman
- Department of Health Science, San Jose State University, San Jose, California, USA
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32
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Latest insights into the hot question of proton pump inhibitor safety - a narrative review. Dig Liver Dis 2020; 52:842-852. [PMID: 32513631 DOI: 10.1016/j.dld.2020.04.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 04/14/2020] [Accepted: 04/17/2020] [Indexed: 02/06/2023]
Abstract
Proton pump inhibitors (PPIs) are among the most widely prescribed medications worldwide and their use is continuously increasing. Although they have been shown to combine high therapeutic efficacy and good safety profile in many studies, in last years we have witnessed the publication of many articles reporting the possible association of long-term PPI therapy with important unexpected adverse events and these observations have created alarmism in both patients and physicians. However, the majority of these studies are observational, retrospective and prone to residual confounding. Also, the odds ratio values are generally comprised between 1 and 2 and therefore devoid of strong clinical relevance. As it is unlikely that prospective randomized trials will be ever done to reinforce these associations, we can only attempt to distinguish clear- from unclear-defined adverse events from the available literature. Nowadays we can reasonably exclude cardiovascular diseases, community-acquired pneumonia, all-cause mortality, dementia and bone fractures from PPI-related adverse events. However, physicians should be aware of the existence of possible risks when treating their patients, especially the elderly and frail ones, with long-term PPIs, which should be prescribed only to persons with defined indications and at lowest dose and duration.
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Abstract
PURPOSE OF REVIEW Proton pump inhibitors (PPIs) are widely prescribed and have excellent short-term tolerability. Administrative database studies have highlighted that many diseases are associated with PPI therapy including pneumonia, fracture, cardiovascular disease, and all-cause mortality. This review therefore reviews the evidence of the risks and benefits of these drugs. RECENT FINDINGS There is high-to-moderate quality evidence that PPIs are effective at treating many acid-related disorders. Recent randomized trials have suggested that the associations between PPIs and various diseases are likely to be related to bias and residual confounding and these drugs appear to be safe apart from a possible increased risk of enteric infections. SUMMARY PPIs should be used at the lowest dose and for the shortest duration possible. They are still relatively well-tolerated drugs but should only be prescribed for proven indications.
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Kurani S, Jeffery MM, Thorsteinsdottir B, Hickson LJ, Barreto EF, Haag J, Giblon R, Shah ND, McCoy RG. Use of Potentially Nephrotoxic Medications by U.S. Adults with Chronic Kidney Disease: NHANES, 2011-2016. J Gen Intern Med 2020; 35:1092-1101. [PMID: 31792867 PMCID: PMC7174522 DOI: 10.1007/s11606-019-05557-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 10/22/2019] [Accepted: 11/11/2019] [Indexed: 01/10/2023]
Abstract
BACKGROUND People with chronic kidney disease (CKD) are at risk for adverse events and/or CKD progression with use of renally eliminated or nephrotoxic medications. OBJECTIVE To examine the prevalence of potentially inappropriate medication (PIM) use by U.S. adults by CKD stage and self-reported CKD awareness. DESIGN Cross-sectional analysis of National Health and Nutrition Examination Surveys, 2011-2016 PARTICIPANTS: Non-pregnant adults with stages 3a (eGFR 45-59 mL/min/1.73 m2), 3b (eGFR 30-44), or 4-5 (eGFR < 30) CKD, stratified as CKD-aware/unaware. MAIN MEASURES PIMs were identified on the basis of KDIGO guidelines, label information, and literature review. We calculated proportions using any and individual PIMs, assessing for differences over CKD awareness within each CKD stage. Analyses were adjusted for age, sex, race/ethnicity, education, comorbidities, and insurance type. KEY RESULTS Adjusted proportions of U.S. adults taking any PIM(s) exceeded 50% for all CKD stages and awareness categories, and were highest among CKD-unaware patients with stages 4-5 CKD: 66.6% (95% CI, 55.5-77.8). Proton pump inhibitors, opioids, metformin, sulfonylureas, and non-steroidal anti-inflammatory drugs (NSAIDs) were all used frequently across CKD stages. NSAIDs were used less frequently when CKD-aware by patients with stage 3a CKD (2.2% [95% CI, - 0.3 to 4.7] vs. 10.7% [95% CI, 7.6 to 13.8]) and stages 4-5 CKD (0.8% [95% CI, - 0.9 to 2.5] vs. 16.5% [95% CI, 4.0 to 29.0]). Metformin was used less frequently when CKD-aware by patients with stage 3b CKD (8.1% [95% CI, 0.3-15.9] vs. 26.5% [95% CI, 17.4-35.7]) and stages 4-5 CKD (none vs. 20.8% [95% CI, 1.8-39.8]). The impact of CKD awareness was statistically significant after correction for multiple comparisons only for NSAIDs in stage 3a CKD. CONCLUSIONS PIMs are frequently used by people with CKD, with some impact of CKD awareness on NSAID and metformin use. This may lead to adverse outcomes or hasten CKD progression, reinforcing the need for improved medication management among people with CKD.
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Affiliation(s)
- Shaheen Kurani
- Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA
| | - Molly Moore Jeffery
- Division of Health Care Policy & Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
| | - Bjorg Thorsteinsdottir
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
- Division of Community Internal Medicine, Department of Medicine, Mayo Clinic, First Street SW, Rochester, MN, USA
| | - LaTonya J Hickson
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
- Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Erin F Barreto
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
- Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - Jordan Haag
- Department of Pharmacy, Mayo Clinic, Rochester, MN, USA
| | - Rachel Giblon
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Nilay D Shah
- Division of Health Care Policy & Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Rozalina G McCoy
- Division of Health Care Policy & Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
- Division of Community Internal Medicine, Department of Medicine, Mayo Clinic, First Street SW, Rochester, MN, USA.
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Tsai IJ, Lai TS, Shiao CC, Huang TM, Wang CH, Tsao CH, Chen LW, Lin YH, Chen L, Wu VC, Chu TS. Proton Pump Inhibitors Augment the Risk of Major Adverse Cardiovascular Events and End-Stage Renal Disease in Patients With Acute Kidney Injury After Temporary Dialysis. Clin Pharmacol Ther 2020; 107:1434-1445. [PMID: 31901200 DOI: 10.1002/cpt.1762] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 11/12/2020] [Indexed: 01/16/2023]
Abstract
Proton pump inhibitors (PPIs) have been reported to increase the risk of acute and chronic renal disease. However, the data are unclear in patients with acute kidney injury (AKI) requiring dialysis (AKI-D) who are often candidates for PPIs. To investigate this important issue, we identified 26,052 AKI-D patients from Taiwan's National Health Insurance Research Database weaning from dialysis. During a mean follow-up period of 3.52 years, the PPI users had a higher incidence of end-stage renal disease (ESRD) than the PPI nonusers (P < 0.001). After propensity score matching and treating mortality as a competing risk factor, the PPI users had a higher risk of ESRD (subhazard ratio (sHR) 1.40; 95% confidence interval (CI), 1.31-1.50) and major adverse cardiac events (MACE, sHR 1.53; 95% CI, 1.37-1.71) compared with the PPI nonusers with AKI-D survivors. In conclusion, the use of PPIs was associated with a higher risk of ESRD and MACE, compared with the PPI nonusers in AKI-D patients who weaned from dialysis.
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Affiliation(s)
- I-Jung Tsai
- Division of Nephrology, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Shuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Chung Shiao
- Division of Nephrology, Department of Internal Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan
| | - Tao-Min Huang
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chih-Hsien Wang
- Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Hao Tsao
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Liang-Wen Chen
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Yen-Hung Lin
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Likwang Chen
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| | - Vin-Cent Wu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzong-Shinn Chu
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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de Godoi Rezende Costa Molino C, Meyer U, Ernst R, Bischoff-Ferrari HA. Proton Pump Inhibitors and Kidney Function Decline in Community-Dwelling Older Adults. J Am Med Dir Assoc 2019; 21:129-130. [PMID: 31784188 DOI: 10.1016/j.jamda.2019.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 10/20/2019] [Indexed: 11/17/2022]
Affiliation(s)
- Caroline de Godoi Rezende Costa Molino
- Department of Geriatric Medicine, University of Zurich, Zurich, Switzerland; Centre on Aging and Mobility, University Hospital Zurich, Stadtspital Waid, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
| | - Ursina Meyer
- Department of Geriatric Medicine, University of Zurich, Zurich, Switzerland; Centre on Aging and Mobility, University Hospital Zurich, Stadtspital Waid, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
| | - Rahel Ernst
- Department of Geriatric Medicine, University of Zurich, Zurich, Switzerland; Centre on Aging and Mobility, University Hospital Zurich, Stadtspital Waid, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
| | - Heike A Bischoff-Ferrari
- Department of Geriatric Medicine, University of Zurich, Zurich, Switzerland; Centre on Aging and Mobility, University Hospital Zurich, Stadtspital Waid, Zurich, Switzerland; University of Zurich, Zurich, Switzerland
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Al-Aly Z, Maddukuri G, Xie Y. Proton Pump Inhibitors and the Kidney: Implications of Current Evidence for Clinical Practice and When and How to Deprescribe. Am J Kidney Dis 2019; 75:497-507. [PMID: 31606235 DOI: 10.1053/j.ajkd.2019.07.012] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 07/12/2019] [Indexed: 12/14/2022]
Abstract
Proton pump inhibitors (PPIs), long thought to be safe, are associated with a number of nonkidney adverse health outcomes and several untoward kidney outcomes, including hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, kidney failure, and increased risk for all-cause mortality and mortality due to chronic kidney disease. PPIs are abundantly prescribed, rarely deprescribed, and frequently purchased over the counter. They are frequently used without medical indication, and when medically indicated, they are often used for much longer than needed. In this In Practice review, we summarize evidence linking PPI use with adverse events in general and adverse kidney outcomes in particular. We review the literature on the association of PPI use and risk for hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, end-stage kidney disease, and death. We provide an assessment of how this evidence should inform clinical practice. We review the impact of this evidence on patients' perception of risk, synthesize PPI deprescription literature, and provide our recommendations on how to approach PPI use and deprescription.
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Affiliation(s)
- Ziyad Al-Aly
- Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, Saint Louis, MO; Nephrology Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, MO; Veterans Research & Education Foundation of St. Louis, Saint Louis, MO; Department of Medicine, Washington University School of Medicine, Saint Louis, MO; Institute for Public Health, Washington University in Saint Louis, Saint Louis, MO.
| | - Geetha Maddukuri
- Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, Saint Louis, MO; Nephrology Section, Medicine Service, VA Saint Louis Health Care System, Saint Louis, MO
| | - Yan Xie
- Clinical Epidemiology Center, Research and Education Service, VA Saint Louis Health Care System, Saint Louis, MO; Veterans Research & Education Foundation of St. Louis, Saint Louis, MO
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Corley DA. Safety and Complications of Long-Term Proton Pump Inhibitor Therapy: Getting Closer to the Truth. Gastroenterology 2019; 157:604-607. [PMID: 31378636 DOI: 10.1053/j.gastro.2019.07.039] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Herzog AL, Lopau K. Interstitielle Nephritis. Internist (Berl) 2019; 60:821-839. [DOI: 10.1007/s00108-019-0634-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Cheema E. Investigating the association of proton pump inhibitors with chronic kidney disease and its impact on clinical practice and future research: a review. J Pharm Policy Pract 2019; 12:6. [PMID: 30976431 PMCID: PMC6440100 DOI: 10.1186/s40545-019-0167-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 03/07/2019] [Indexed: 01/04/2023] Open
Abstract
Background Proton pump inhibitors (PPIs) are used worldwide for the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). Although considered to be widely safe, PPIs have been associated with the potential risk of adverse effects such as infections including pneumonia and Clostridium difficile, malabsorption of vitamins and minerals, dementia and more recently with chronic kidney disease (CKD). Evidence including large cohort studies suggests that there is a greater risk of developing CKD in chronic users of PPIs. However, the association of CKD with PPI use reported in these studies is weak and does not establish a clear causality. This review aims to further investigate the association of CKD with PPI use by including studies with various study designs. Methods A literature search of published articles with no start date restrictions was undertaken in May 2018 in three electronic databases (PubMed, ScienceDirect, Google Scholar). Search terms included ‘Proton Pump Inhibitors’, ‘chronic kidney disease’, and ‘association’. Both observational and randomised controlled trials (RCTs) investigating the association of CKD with PPI use were eligible for inclusion. Results Ten observational studies with 1,005,899 patients contributed to the review. No experimental study was available for inclusion in the review. Of the included studies, six used a retrospective study design, while the rest were prospective (two) or a case-controlled studies (two). A large prospective cohort study with 144,032 patients conducted in the USA reported that PPI use compared to no PPI use was associated with an increased risk of CKD Hazard ratio [HR] 1.28; 95% Confidence Interval [CI] 1.22–1.34. However, the observational study design of this study together with other studies included in the review suggests that the strength of evidence associating PPI use with CKD is weak and does not establish true causality. Conclusions The current evidence related to the potential association of CKD with PPI use remains inconclusive in establishing true causality. Further prospective studies including randomised controlled trials and cohort studies would be required to confirm the findings reported in this review and to draw any conclusions.
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Affiliation(s)
- Ejaz Cheema
- Institute of clinical sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT UK
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