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Miyazaki Y, Iwama E, Ogata H, Ibusuki R, Shibahara D, Otsubo K, Shiaraishi Y, Yoneshima Y, Torisu K, Okamoto I. Renal dysfunction during osimertinib treatment in patients with non-small cell lung cancer positive for EGFR mutations. Respir Investig 2025; 63:438-443. [PMID: 40174243 DOI: 10.1016/j.resinv.2025.03.015] [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: 12/12/2024] [Revised: 02/25/2025] [Accepted: 03/23/2025] [Indexed: 04/04/2025]
Abstract
BACKGROUND Osimertinib is a standard treatment for non-small cell lung cancer (NSCLC) positive for EGFR activating mutations. Although renal dysfunction associated with osimertinib treatment is reported to be rare, detailed information on this adverse effect is needed because cytotoxic drugs such as pemetrexed are also widely administered for NSCLC but cannot be used in individuals with renal dysfunction. METHODS We retrospectively collected clinical data including the serum creatinine concentration and estimated glomerular filtration rate (eGFR) during osimertinib treatment for 130 NSCLC patients. RESULTS Serum creatinine and eGFR worsened gradually during osimertinib treatment, with the median value of creatinine at the point of greatest deterioration differing significantly from that at baseline (0.93 versus 0.72 mg/dL, P < 0.01). Seventy patients (54 %) experienced worsening of the CTCAE grade for creatinine increased, with the frequency of patients with grade 1 or 2 being increased significantly (P < 0.01) at the point of greatest deterioration relative to baseline (grade 1, 46.9 % versus 14.6 %; grade 2, 14.6 % versus 0.8 %, respectively). A higher serum creatinine level at baseline was a significant risk factor for worsening of the CTCAE grade (odds ratio of 1.66, P < 0.001). The median serum creatinine and eGFR at 4 weeks after osimertinib discontinuation had improved to levels similar to those for baseline. CONCLUSIONS Renal dysfunction occurred frequently during osimertinib treatment but was ameliorated after drug discontinuation, suggesting that, although renal function should be carefully monitored, its impairment is not likely to affect subsequent chemotherapy in most patients.
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Affiliation(s)
- Yui Miyazaki
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Eiji Iwama
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
| | - Hiroaki Ogata
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Ritsu Ibusuki
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Daisuke Shibahara
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kohei Otsubo
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshimasa Shiaraishi
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yasuto Yoneshima
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kumiko Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan; Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Isamu Okamoto
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Miedziaszczyk M, Karczewski M, Idasiak-Piechocka I. The effect of the use of omeprazole versus famotidine on the kidney transplant function: a randomized controlled study. Sci Rep 2025; 15:1805. [PMID: 39805983 PMCID: PMC11730594 DOI: 10.1038/s41598-025-85534-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 01/03/2025] [Indexed: 01/16/2025] Open
Abstract
Tacrolimus is metabolized in the liver with the participation of cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5). Omeprazole, unlike famotidine, is a substrate and inhibitor of CYP2C19, CYP3A4, CYP3A5 enzymes. The aim of the study is to compare the effect of omeprazole and famotidine on the tacrolimus concentration and the kidney transplant function. A randomized study was conducted in 24 adult patients with stable kidney transplant function who received a standard triple immunosuppression regimen. Patients were assigned to the group I (n = 12) additionally receiving omeprazole (20 mg) or the group II (n = 12) receiving famotidine (20 mg). At the time of qualification and during follow-up visits, tacrolimus blood concentration and selected laboratory tests were performed. Statistical analysis was performed using the MedCalc system. The value of tacrolimus concentration in the blood increased after a year in the group I (7.27 ± 2.33 vs 9.20 ± 2.46 ng/mL, p = 0.0478). A reduction in tacrolimus dosage was observed after three years in the group I (3.56 ± 1.75 vs 2.78 ± 1.00 mg, p = 0.0440) and in the group II (2.72 ± 0.84 vs 2.10 ± 0.48 mg, p = 0.0051). There was significant difference in the percentage changes of glomerular filtration rate between the groups after 3 years of the study (- 5.56% vs 9.13%, p = 0.0343). Omeprazole significantly change the concentration of tacrolimus in the blood when administered together with tacrolimus after one year of observation. There was no effect of famotidine or omeprazole on the function of the kidney transplant. ClinicalTrials.gov identifier: NCT05061303.
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Affiliation(s)
- Miłosz Miedziaszczyk
- Department of General and Transplant Surgery, Poznan University of Medical Sciences, 61-701, Poznan, Poland.
- Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, 61-701, Poznan, Poland.
| | - Marek Karczewski
- Department of General and Transplant Surgery, Poznan University of Medical Sciences, 61-701, Poznan, Poland
| | - Ilona Idasiak-Piechocka
- Department of General and Transplant Surgery, Poznan University of Medical Sciences, 61-701, Poznan, Poland
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Zhou X, Duan H, Li Q, Wang Q, Sun X. Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: a systematic review and meta-analysis. Scand J Gastroenterol 2024; 59:788-797. [PMID: 38741565 DOI: 10.1080/00365521.2024.2349638] [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: 12/09/2023] [Revised: 03/30/2024] [Accepted: 04/24/2024] [Indexed: 05/16/2024]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.
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Affiliation(s)
- Xinxu Zhou
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Hui Duan
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Qian Li
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Qiong Wang
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
| | - Xiaobin Sun
- Department of Gastroenterology of The Third People's Hospital of Chengdu, Chengdu, China
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Weir MR. Proton Pump Inhibitors and Kidney Disease: Fact or Fiction? Am J Nephrol 2024; 55:499-508. [PMID: 38583423 DOI: 10.1159/000538755] [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: 02/07/2024] [Accepted: 04/05/2024] [Indexed: 04/09/2024]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are commonly prescribed medications for dyspepsia and gastroesophageal reflux. There are concerns about their use in the development of chronic kidney disease (CKD). SUMMARY The available published literature fails to support an association with PPI and the development of CKD. Placebo-controlled trials demonstrate no difference in the incidence of CKD between placebo and PPI. If one examines the data according to the Bradford Hill perspective incorporating temporal relationship, the strength of association, dose-response relationship, replacement of findings, cessation of exposure, specificity of the association, and consistency with other knowledge, one can only conclude that there is no consistent relationship between PPI use and the development of CKD, or its progression. KEY MESSAGES There is insufficient evidence to link PPI exposure with the development or progression of CKD.
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Affiliation(s)
- Matthew R Weir
- Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, 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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Suzuki K, Watanabe A, Kiryu Y, Inoue E, Momo K. Self-controlled Case Series Study for Acute Kidney Injury after Starting Proton Pump Inhibitors or Potassium-Competitive Acid Blocker in Patients with Cancer Using a Large Claims Database. Biol Pharm Bull 2024; 47:518-526. [PMID: 38403662 DOI: 10.1248/bpb.b23-00676] [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] [Indexed: 02/27/2024]
Abstract
To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.
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Affiliation(s)
- Kosuke Suzuki
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
- Department of Pharmacy, Showa University Hospital
| | - Ayako Watanabe
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
- Department of Pharmacy, Showa University Koto Toyosu Hospital
| | - Yoshihiro Kiryu
- Department of Pharmacy, M&B Collaboration Medical corporation Hokuetsu Hospital
| | - Eisuke Inoue
- Showa University Research Administration Center, Showa University
| | - Kenji Momo
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
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Miao J, Herrmann SM. Immune checkpoint inhibitors and their interaction with proton pump inhibitors-related interstitial nephritis. Clin Kidney J 2023; 16:1834-1844. [PMID: 37915905 PMCID: PMC10616479 DOI: 10.1093/ckj/sfad109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Indexed: 11/03/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can cause a spectrum of immune-related adverse events (irAEs). Essentially, any organs can be affected by irAEs, which have emerged as therapy-limiting side effects. In the kidneys, ICI-associated acute interstitial nephritis (ICI-AIN) leads to acute kidney injury (AKI) in 2%-5% of patients on ICI therapy. AKI associated with ICI therapy pathologically presents with AIN in nearly 90% of the cases, but the pathophysiology of ICI-AIN remains to be defined. The generation of autoreactive T cells in patients receiving AIN-inducible drugs, such as proton pump inhibitors (PPIs), is one of the leading theories, supported by a higher incidence of ICI-AIN in patients on these AIN-inducible drugs. In this review, we will discuss our understanding of the incidence, potential pathophysiological mechanisms, clinical presentations, risk factors, diagnosis, and management of PPI-related AIN and its interaction with ICI therapy.
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Affiliation(s)
- Jing Miao
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA
| | - Sandra M Herrmann
- Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, 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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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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Begg M, Tarhuni M, N Fotso M, Gonzalez NA, Sanivarapu RR, Osman U, Latha Kumar A, Sadagopan A, Mahmoud A, Khan S. Comparing the Safety and Efficacy of Proton Pump Inhibitors and Histamine-2 Receptor Antagonists in the Management of Patients With Peptic Ulcer Disease: A Systematic Review. Cureus 2023; 15:e44341. [PMID: 37779765 PMCID: PMC10538946 DOI: 10.7759/cureus.44341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/29/2023] [Indexed: 10/03/2023] Open
Abstract
Peptic ulcer disease (PUD) refers to the occurrence of an open erosion in the inner lining of the stomach, duodenum, or sometimes lower esophagus. Treatments like proton pump inhibitors (PPIs) or histamine 2 receptor antagonists (H2RAs) are available on the market to efficiently treat the break in the mucosal lining. However, there is little evidence about the effects of the medication on the type and location of the ulcer and the epigastric pain caused by disintegration and increased acidity in the stomach. Given the above, we conducted a systematic review comparing the safety and efficacy of PPIs and H2RAs in various ulcer locations (gastric, duodenal, and pre-pyloric) and the effect of prolonging the treatment with the same medication or changing into a drug from another class in treatment-resistant ulcers. We employed major research literature databases and search engines such as PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, and Google Scholar to find relevant articles. After a thorough screening, a quality check using various tools, and applying filters that suited our eligibility criteria, we identified eight articles, of which five were random clinical trials (RCTs), two review articles, and one meta-analysis. This study compares the different side effects of PPIs and H2RAs. Most studies concluded that omeprazole is superior in healing ulcers and bringing pain relief and that patients resistant to H2RAs can be treated better when switched to a PPI. This study also discusses the adverse effects of chronic use, such as diarrhea, constipation, headaches, and gastrointestinal infections. Patients on long-term PPI therapy are required to take calcium supplements to prevent the risk of fractures in older adults. Regarding long-term outcomes, PPIs remain the mainstay of treatment for peptic ulcer disease, based on the papers we reviewed.
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Affiliation(s)
- Maha Begg
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mawada Tarhuni
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfiled, USA
| | - Monique N Fotso
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Natalie A Gonzalez
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Raghavendra R Sanivarapu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfiled, USA
| | - Usama Osman
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abishek Latha Kumar
- Internal Medicine, Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aishwarya Sadagopan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Anas Mahmoud
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfiled, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Ngwenya S, Simin J, Brusselaers N. Maintenance Proton Pump Inhibitor Use Associated with Increased All-Cause and Cause-Specific Mortality in Sweden. Dig Dis Sci 2023; 68:2252-2263. [PMID: 36629968 PMCID: PMC10188584 DOI: 10.1007/s10620-023-07820-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 12/31/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Proton pump inhibitor (PPI) use has increased over the last decades and has been associated with multiple adverse events and potentially even overall survival. AIMS We aimed to investigate the association between proton pump inhibitor maintenance use and all-cause and cause-specific mortality, addressing confounding by indication and duration of use. METHODS This Swedish population-based cohort study included all adult (N = 935,236) PPI and histamine-2 receptor antagonist maintenance users (≥ 180 days use) during 2005-2014. Standardised mortality ratios (SMRs) and 95% confidence intervals were calculated for all-cause and cause-specific mortality comparing the risk among PPI/H2RA users to that of the Swedish background population, stratified by age, sex, calendar period, indication and duration of use. Multivariable Poisson regression models were used to compare PPI use to H2RA use, expressed as incidence rate ratios and 95% confidence intervals. RESULTS PPI and histamine-2 receptor antagonist use were associated with an increased risk of all-cause mortality (SMR = 1.35; 1.34-1.36; SMR = 1.31; 1.27-1.36, respectively). The highest SMRs were found in the youngest age groups. In direct comparison, PPI use showed a higher mortality risk than histamine-2 receptor antagonist use (incidence rate ratios = 1.42; 1.38-1.46). PPIs were related to increased cancer (SMR = 1.21; 1.20-1.22), and cardiovascular mortality (SMR = 1.36; 1.35-1.37). Increased SMRs were observed for most indications. Longer duration of use was associated with a higher mortality among PPI users but not among histamine-2 receptor antagonist users. CONCLUSION Maintenance PPI use was associated with an increased risk of all-cause and cause-specific mortality, and the risk increased with prolonged duration.
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Affiliation(s)
- Sharon Ngwenya
- Centre for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Biomedicum A8, Solnavägen 9, 171 65 Stockholm, Sweden
- Department of Family Medicine and Population Health, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
| | - Johanna Simin
- Centre for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Biomedicum A8, Solnavägen 9, 171 65 Stockholm, Sweden
| | - Nele Brusselaers
- Centre for Translational Microbiome Research, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Biomedicum A8, Solnavägen 9, 171 65 Stockholm, Sweden
- Department of Family Medicine and Population Health, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium
- Department of Head and Skin, Ghent University, Corneel Heymanslaan 10, 9000 Ghent, Belgium
- Centre for Translational Microbiome Research, Solnavägen 9, 171 76 Stockholm, Sweden
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12
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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: 4] [Impact Index Per Article: 2.0] [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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13
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Meng R, Chen LR, Zhang ML, Cai WK, Yin SJ, Fan YX, Zhou T, Huang YH, He GH. Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta-Analyses. J Clin Pharmacol 2023; 63:7-20. [PMID: 36039014 DOI: 10.1002/jcph.2147] [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: 06/16/2022] [Accepted: 08/24/2022] [Indexed: 12/15/2022]
Abstract
Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.
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Affiliation(s)
- Rui Meng
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
- Kunming Medical University, Kunming, China
| | - Li-Rong Chen
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Man-Li Zhang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
- Kunming Medical University, Kunming, China
| | - Wen-Ke Cai
- Department of Cardio-Thoracic Surgery, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Sun-Jun Yin
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Yu-Xin Fan
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Tao Zhou
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Yan-Hua Huang
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
| | - Gong-Hao He
- Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force of People's Liberation Army, Kunming, China
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14
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Zhang XY, He QS, Jing Z, He JX, Yuan JQ, Dai XY. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank. Front Pharmacol 2022; 13:949699. [PMID: 36438798 PMCID: PMC9685407 DOI: 10.3389/fphar.2022.949699] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 10/25/2022] [Indexed: 02/07/2024] Open
Abstract
Background: Proton pump inhibitors (PPIs) are widely used and have been linked to kidney diseases. However, the role of PPI use in the development of chronic kidney disease (CKD) remains unclear. We undertook this study to examine the association between PPI use and the subsequent risk of CKD. Methods: This is a prospective analysis of 462,421 participants free of cancer diagnosis or chronic kidney disease from the United Kingdom Biobank. Self-reported PPI use was recorded using an electronic questionnaire and confirmed by a trained staff. Incident CKD was identified based on the medical history. Overlap propensity score weighting with the Cox model was used to calculate the effect of PPI use on CKD risk. The number needed to harm (NNH) was calculated at 5 and 10 years of follow-up. Results: We documented 7,031 cases of CKD over a median follow-up of 8.1 years. Overlap propensity score weighting analysis showed that regular PPI users had a 37% higher risk of CKD incident than non-users (HR 1.37, 95% CI 1.28-1.47). The association persisted across subgroup analyses, different types of PPIs, and several sensitivity analyses. Quantitative bias analysis indicated that the result was robust to unmeasured confounding (E-value 2.08, lower 95% CI 1.88). The NNH was 147.9 and 78.6 for 5 and 10 years of follow-up, respectively. A head-to-head comparison showed that PPI users had a 19% higher risk of CKD than H2RA users (HR 1.19, 95% CI 1.02-1.39). Conclusion: The regular use of PPI is associated with a higher risk of CKD. Healthcare providers should carefully weigh up the potential benefits against the risk in prescribing PPIs, particularly for patients requiring long-term treatment.
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Affiliation(s)
- Xing-Yu Zhang
- Department of Nephrology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
| | - Qiang-Sheng He
- Clinical Research Center, Guangdong; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Zhong Jing
- Department of Nephrology, Mianyang 404 Hospital, Mianyang, China
| | - Juan-Xia He
- Department of Information Engineering, University of Lanzhou City, Lanzhou, China
| | - Jin-Qiu Yuan
- Clinical Research Center, Guangdong; Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiao-Yu Dai
- Department of Nephrology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China
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15
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Leowattana W, Leowattana T. Potassium-competitive acid blockers and gastroesophageal reflux disease. World J Gastroenterol 2022; 28:3608-3619. [PMID: 36161043 PMCID: PMC9372813 DOI: 10.3748/wjg.v28.i28.3608] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 04/24/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer disease, and relegate anti-reflux surgery to patients with gastroesophageal reflux disease (GERD) who are inadequately managed by medical therapy. However, PPI medications still leave some therapeutic demands of GERD unmet. Furthermore, up to 40%-55% of daily PPI users have chronic symptoms, due to PPI refractoriness. Potassium-competitive acid blockers (P-CABs) transcend many of the problems and limits of PPIs, delivering quick, powerful, and extended acid suppression and allowing for treatment of numerous unmet needs. Recently, it has become clear that compromised mucosal integrity plays a role in the etiology of GERD. As a result, esophageal mucosal protection has emerged as a novel and potential treatment approach. An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs (to regular treatment), they provide a considerable extra benefit, particularly in alleviating symptoms that do not respond to PPI therapy.
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Affiliation(s)
- Wattana Leowattana
- Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Tawithep Leowattana
- Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
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16
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Subramaniam A, Wengritzky R, Skinner S, Shekar K. Colorectal Surgery in Critically Unwell Patients: A Multidisciplinary Approach. Clin Colon Rectal Surg 2022; 35:244-260. [PMID: 35966378 PMCID: PMC9374534 DOI: 10.1055/s-0041-1740045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
A proportion of patients require critical care support following elective or urgent colorectal procedures. Similarly, critically ill patients in intensive care units may also need colorectal surgery on occasions. This patient population is increasing in some jurisdictions given an aging population and increasing societal expectations. As such, this population often includes elderly, frail patients or patients with significant comorbidities. Careful stratification of operative risks including the need for prolonged intensive care support should be part of the consenting process. In high-risk patients, especially in setting of unplanned surgery, treatment goals should be clearly defined, and appropriate ceiling of care should be established to minimize care that is not in the best interest of the patient. In this article we describe approaches to critically unwell patients requiring colorectal surgery and how a multidisciplinary approach with proactive intensive care involvement can help achieve the best outcomes for these patients.
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Affiliation(s)
- Ashwin Subramaniam
- Department of Intensive Care Medicine, Peninsula Health, Frankston, Victoria, Australia
- Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
- Department of Intensive Care, The Bays Healthcare, Mornington, Victoria, Australia
| | - Robert Wengritzky
- Department of Anaesthesia, Peninsula Health, Frankston, Victoria, Australia
| | - Stewart Skinner
- Department of Surgery, Peninsula Health, Frankston, Victoria, Australia
| | - Kiran Shekar
- Adult Intensive Care Services, the Prince Charles Hospital, Brisbane, Queensland, Australia
- Queensland University of Technology, University of Queensland, Brisbane, Queensland, Australia
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17
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Rajan P, Iglay K, Rhodes T, Girman CJ, Bennett D, Kalantar-Zadeh K. Risk of bias in non-randomized observational studies assessing the relationship between proton-pump inhibitors and adverse kidney outcomes: a systematic review. Therap Adv Gastroenterol 2022; 15:17562848221074183. [PMID: 35173802 PMCID: PMC8841917 DOI: 10.1177/17562848221074183] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 12/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) are widely prescribed as acid-suppression therapy. Some observational studies suggest that long-term use of PPIs is potentially associated with certain adverse kidney outcomes. We conducted a systematic literature review to assess potential bias in non-randomized studies reporting on putative associations between PPIs and adverse kidney outcomes (acute kidney injury, acute interstitial nephritis, chronic interstitial nephritis, acute tubular necrosis, chronic kidney disease, and end-stage renal disease). METHODS We searched the medical literature within 10 years of 17 December 2020. Pre-specified criteria guided identification of relevant English language articles for assessment. Risk of bias on an outcome-specific basis was evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool by two independent reviewers. RESULTS Of 620 initially identified records, 26 studies met a priori eligibility criteria and underwent risk of bias assessment. Nineteen studies were judged as having a moderate risk of bias for reported adverse kidney outcomes, while six studies were judged as having a serious risk of bias (mainly due to inadequate control of confounders and selection bias). We were unable to determine the overall risk of bias in two studies (one of which was assessed as having a moderate risk of bias for a different adverse kidney outcome) due to insufficient information presented. Effect estimates for PPIs in relation to adverse kidney outcomes varied widely (0.24-7.34) but associations mostly showed increased risk. CONCLUSION Using ROBINS-I, we found that non-randomized observational studies suggesting kidney harm by PPIs have moderate to serious risk of bias, making it challenging to establish causality. Additional high-quality, real-world evidence among generalizable populations are needed to better understand the relation between PPI treatment and acute and chronic kidney outcomes, accounting for the effects of varying durations of PPI treatment, self-treatment with over-the-counter PPIs, and potential critical confounders.
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Affiliation(s)
- Pradeep Rajan
- CERobs Consulting, LLC, 2612 N Lumina Beach, Wrightsville Beach, NC, USA
| | - Kristy Iglay
- CERobs Consulting, LLC, Wrightsville Beach, NC, USA
| | | | | | - Dimitri Bennett
- Global Evidence and Outcomes, Takeda Pharmaceuticals USA, Inc., Cambridge, MA, USA
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Kamyar Kalantar-Zadeh
- Division of Nephrology, Hypertension & Kidney Transplantation, School of Medicine, University of California, Irvine, Irvine, CA, USA
- Department of Epidemiology, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA
- Tibor Rubin Veterans Administration Long Beach Healthcare System, Long Beach, CA, USA
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18
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Franciosi JP, Mougey EB, Dellon ES, Gutierrez-Junquera C, Fernandez-Fernandez S, Venkatesh RD, Gupta SK. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy 2022; 15:281-302. [PMID: 35250281 PMCID: PMC8892718 DOI: 10.2147/jaa.s274524] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/14/2022] [Indexed: 12/11/2022] Open
Abstract
Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.
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Affiliation(s)
- James P Franciosi
- Division of Gastroenterology, Nemours Children’s Hospital, Orlando, FL, USA
- College of Medicine, University of Central Florida, Orlando, FL, USA
- Correspondence: James P Franciosi, Division of Gastroenterology, Nemours Children’s Hospital, 6535 Nemours Parkway, Orlando, FL, 32827, USA, Email
| | - Edward B Mougey
- Center for Pharmacogenomics and Translational Research, Nemours Children’s Health System, Jacksonville, FL, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carolina Gutierrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Autonomous University of Madrid, Madrid, Spain
| | | | - Rajitha D Venkatesh
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Sandeep K Gupta
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine and Community Health Network, Indianapolis, IN, USA
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19
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ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022; 117:27-56. [PMID: 34807007 PMCID: PMC8754510 DOI: 10.14309/ajg.0000000000001538] [Citation(s) in RCA: 423] [Impact Index Per Article: 141.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/30/2021] [Indexed: 01/30/2023]
Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
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20
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Salvo EM, Ferko NC, Cash SB, Gonzalez A, Kahrilas PJ. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther 2021; 54:129-143. [PMID: 34114655 DOI: 10.1111/apt.16407] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/04/2020] [Accepted: 04/30/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. AIMS To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. METHODS In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. RESULTS Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. CONCLUSIONS This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.
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Affiliation(s)
- Elizabeth M Salvo
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Nicole C Ferko
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Sarah B Cash
- Value & Evidence Division, Marketing and Market Access, EVERSANA, Burlington, ON, Canada
| | - Ailish Gonzalez
- Health Economics and Market Access, Ethicon Inc, Somerville, NJ, USA
| | - Peter J Kahrilas
- Feinberg School of Medicine at Northwestern University, Chicago, IL, USA
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21
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Hatakeyama Y, Horino T, Matsumoto T, Terada Y, Okuhara Y. Long-term continuous use of proton-pump inhibitors is associated with renal function decline in patients without acute kidney injury. Clin Exp Nephrol 2021; 25:1087-1092. [PMID: 34089392 DOI: 10.1007/s10157-021-02066-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 04/19/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) are widely used to treat gastroesophageal reflex disease, peptic ulcer disease, and stress ulcer prophylaxis. This study estimated the progress rate of renal dysfunction in patients taking PPIs in clinical settings and compared the results with those of patients taking histamine-2 receptor antagonists (H2RAs). METHODS We retrospectively reviewed patients' data collected from Kochi Medical School Hospital's information system between 2001 and 2019. Patients were classified into PPI and H2RA groups, and survival time was defined as the period between initial drug administration and a 30% decrease in estimated glomerular filtration rate (eGFR). RESULTS On survival analysis, the PPI group was associated with higher event incidence rates compared to that in the H2RA group. The rate of underlying disease was significantly higher in the PPI group than in the H2RA group, with no significant differences in age and sex between the groups. Comparing the PPI group to the H2RA group, the use of aspirin, clopidogrel, statin, and angiotensin II receptor blocker was significantly higher, whereas the use of non-steroidal anti-inflammatory drugs and steroids was significantly less. Regarding survival rate and 30% decrease in eGFR, the PPI group had a significantly higher survival rate compared to that in the H2RA group at 730 days, but not earlier. PPI use, older age, and eGFR ≥ 90 mL/min/1.73 m2 exhibited high hazard ratios. CONCLUSIONS PPI use was significantly associated with an increased risk of chronic kidney disease development compared to that with H2RA use.
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Affiliation(s)
- Yutaka Hatakeyama
- Center of Medical Information Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Japan
| | - Taro Horino
- Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
| | - Tatsuki Matsumoto
- Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Yoshio Terada
- Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan
| | - Yoshiyasu Okuhara
- Center of Medical Information Science, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Japan
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22
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Yibirin M, De Oliveira D, Valera R, Plitt AE, Lutgen S. Adverse Effects Associated with Proton Pump Inhibitor Use. Cureus 2021; 13:e12759. [PMID: 33614352 PMCID: PMC7887997 DOI: 10.7759/cureus.12759] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2021] [Indexed: 12/13/2022] Open
Abstract
Proton pump inhibitors (PPIs) marked a before and after in the management of gastric acid-related disorders since their introduction to the market in 1989. Due to a novel, highly effective mechanism of action blocking the last converging step of gastric acid secretion by parietal cells and very few and mostly tolerable side effects, these drugs quickly displaced other pharmacological compounds such as H2 antagonists as the first treatment choice for peptic ulcer disease, gastroesophageal ulcers, Zollinger-Ellison syndrome, nonsteroidal anti-inflammatory drug-associated ulcers, and eradication of Helicobacter pylori, leading to an exponential increase in their prescription up to now. However, widespread PPI use has led to emerging evidence of long-term adverse effects not described previously, including increased risk of kidney, liver, and cardiovascular disease, dementia, enteroendocrine tumors of the gastrointestinal tract, susceptibility to respiratory and gastrointestinal infections, and impaired absorption of nutrients. Although the evidence published thus far has not established strong correlations, it has been relevant enough to raise new questions about PPIs' safety profile and reconsideration of their clinical indications. Hence, the aim of this review is to evaluate the association between PPI use and the risk of serious adverse effects given increasing concerns about the overuse of PPIs in the general population.
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Affiliation(s)
- Marcel Yibirin
- Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston, USA
| | - Diana De Oliveira
- Department of Research, Foundation for Clinic, Public Health, and Epidemiological Research of Venezuela (FISPEVEN), Caracas, VEN
| | - Roberto Valera
- Department of General Surgery, Cleveland Clinic Florida, Weston, USA
| | - Andrea E Plitt
- Critical Care, Dr. Ignacio Pirovano Hospital, Buenos Aires, ARG
| | - Sophia Lutgen
- Internal Medicine, Dr Juan A. Fernández Hospital, Buenos Aires, ARG
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Abstract
PURPOSE OF REVIEW This review explores the recent evidence and established scientific literature surrounding proton pump inhibitors in the context of laryngology. RECENT FINDINGS Proton pump inhibitors are often associated with gastroenterology; however, they also have a place in laryngology. Several laryngopharyngeal disorders are treated with proton pump inhibitors, though limited evidence regarding effectiveness, dosing and length of treatment exists. With the recent influx of articles reporting possible adverse effects of proton pump inhibitors, the appropriate prescribing of them has come under scrutiny. These reported risks include cancer, stroke, myocardial infarction, kidney disease and cognitive decline. It should be noted though that many of these studies by nature, are fraught with potential confounding. Regardless, clinicians ought to be aware of any risks associated with treatment regimens and prescribe the optimal dosage and duration. SUMMARY Proton pump inhibitor treatment should be dose-appropriate and for a limited duration. Concerning potential adverse effects, the limitations of retrospective cohort studies must be taken into consideration when reviewing the evidence.
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Moledina DG, Wilson FP, Kukova L, Obeid W, Luciano R, Kuperman M, Moeckel GW, Kashgarian M, Perazella MA, Cantley LG, Parikh CR. Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis. Nephrol Dial Transplant 2020; 36:1851-1858. [PMID: 33125471 DOI: 10.1093/ndt/gfaa169] [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: 12/09/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. METHODS In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. RESULTS In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. CONCLUSIONS Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.
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Affiliation(s)
- Dennis G Moledina
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA.,Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT, USA
| | - F Perry Wilson
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA.,Clinical and Translational Research Accelerator, Yale School of Medicine, New Haven, CT, USA
| | | | - Wassim Obeid
- Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Randy Luciano
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA
| | | | - Gilbert W Moeckel
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | | | - Mark A Perazella
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA
| | - Lloyd G Cantley
- Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, CT, USA
| | - Chirag R Parikh
- Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
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25
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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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26
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Molnar AO, Bota S, Jeyakumar N, McArthur E, Battistella M, Garg AX, Sood MM, Brimble KS. Potentially inappropriate prescribing in older adults with advanced chronic kidney disease. PLoS One 2020; 15:e0237868. [PMID: 32818951 PMCID: PMC7444541 DOI: 10.1371/journal.pone.0237868] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 08/04/2020] [Indexed: 12/13/2022] Open
Abstract
Background Older adults with chronic kidney disease (CKD) are at heightened risk for polypharmacy. We examined potentially inappropriate prescribing in this population and whether introducing pharmacists into the ambulatory kidney care model was associated with improved prescribing practices. Methods Retrospective cohort study using linked administrative databases. We included patients with an eGFR ≤30 mL/min/1.73 m2 ≥66 years of age followed in multidisciplinary kidney clinics in Ontario, Canada (n = 25,016 from 28 centres). The primary outcome was the absence of a statin prescription or the receipt of a potentially inappropriate prescription defined by the American Geriatric Society Beers Criteria® and a modified Delphi panel that identified key drugs of concern in CKD. We calculated the crude cumulative incidence and incidence rate for the primary outcome and used change-point regression to determine if a change occurred following pharmacist introduction. Results There were 6,007 (24%) and 16,497 patients (66%) not prescribed a statin and with ≥1 potentially inappropriate prescription, respectively. The rate of potentially inappropriate prescribing was 125.6 per 100 person-years and was higher in more recent years. The change-point regression analysis included 2,275 patients from two centres. No immediate change was detected at pharmacist introduction, but potentially inappropriate prescribing was increasing pre-pharmacist introduction, and this rising trend was reversed post-pharmacist introduction. The incidence of potentially inappropriate prescribing still remained high post-pharmacist introduction. Conclusions Potentially inappropriate prescribing practices were common. Incorporating pharmacists into the kidney care model may improve prescribing practices. The role of pharmacists in the ambulatory kidney care team warrants further investigation in a randomized controlled trial.
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Affiliation(s)
- Amber O. Molnar
- Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- * E-mail:
| | | | | | | | - Marisa Battistella
- University Health Network/Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
| | - Amit X. Garg
- Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada
| | - Manish M. Sood
- Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Canada
- Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - K. Scott Brimble
- Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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27
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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: 23] [Impact Index Per Article: 4.6] [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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28
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Kaur G, Krishan P. Serotonin 5HT 2A receptor antagonism mediated anti-inflammatory and anti-fibrotic effect in adriamycin-induced CKD in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2020; 393:1269-1279. [PMID: 32342136 DOI: 10.1007/s00210-020-01826-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 01/17/2020] [Indexed: 02/07/2023]
Abstract
A selective 5-HT2A receptor antagonist ketanserin has been used preclinically to improve renal blood flow because of its beneficial effect on autoregulation in various chronic kidney disease models. Ketanserin might be able to turn down adriamycin-induced chronic kidney disease, which is characterized by renal fibrosis, inflammation and structural and functional changes in glomeruli. In the present study, we investigated whether ketanserin suppresses these renal alterations or not. Wistar rats were administered with a single dose of adriamycin (6 mg/kg/i.v), which leads to development of severe tubulointerstitial fibrosis with altered renal function. Subsequent ketanserin treatment (5 mg/kg/p.o) for 4 weeks shown significant change in oxidative stress, serum and urine parameters in adriamycin-induced chronic kidney disease rats. Additionally, results showed that mRNA expression of TGF-β and collagen IV, which are known to promote fibrosis via various signaling pathways involved in the progression of renal disease, was suppressed by ketanserin treatment. Furthermore, expression levels of 5-HT2A and pro-inflammatory marker IL-6 have also been reduced significantly after ketanserin administration in adriamycin-treated animals. Moreover, histopathological studies also reveal the considerable structural changes after ketanserin treatment, and these results are further supported via data obtained from the percentage of glomeruli size changes. In conclusion, ketanserin reduces renal fibrosis and inflammation in adriamycin-induced chronic kidney disease by suppressing 5-HT2A, IL-6, TGF-β and collagen IV expression in renal tissue.
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Affiliation(s)
- Gagandeep Kaur
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India
| | - Pawan Krishan
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India.
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29
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Thongprayoon C, Kaewput W, Kovvuru K, Hansrivijit P, Kanduri SR, Bathini T, Chewcharat A, Leeaphorn N, Gonzalez-Suarez ML, Cheungpasitporn W. Promises of Big Data and Artificial Intelligence in Nephrology and Transplantation. J Clin Med 2020; 9:1107. [PMID: 32294906 PMCID: PMC7230205 DOI: 10.3390/jcm9041107] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 04/09/2020] [Indexed: 02/07/2023] Open
Abstract
Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as "big data", has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.
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Affiliation(s)
- Charat Thongprayoon
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; (C.T.); (A.C.)
| | - Wisit Kaewput
- Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand;
| | - Karthik Kovvuru
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.); (M.L.G.-S.)
| | - Panupong Hansrivijit
- Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA 17105, USA;
| | - Swetha R. Kanduri
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.); (M.L.G.-S.)
| | - Tarun Bathini
- Department of Internal Medicine, University of Arizona, Tucson, AZ 85721, USA;
| | - Api Chewcharat
- Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; (C.T.); (A.C.)
| | - Napat Leeaphorn
- Department of Nephrology, Department of Medicine, Saint Luke’s Health System, Kansas City, MO 64111, USA;
| | - Maria L. Gonzalez-Suarez
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.); (M.L.G.-S.)
| | - Wisit Cheungpasitporn
- Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; (K.K.); (S.R.K.); (M.L.G.-S.)
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Schnoll-Sussman F, Niec R, Katz PO. Proton Pump Inhibitors: The Good, Bad, and Ugly. Gastrointest Endosc Clin N Am 2020; 30:239-251. [PMID: 32146944 DOI: 10.1016/j.giec.2019.12.005] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Proton pump inhibitors (PPIs) continue to be the medication of choice for treatment of acid-related disease, with few if any overt side effects seen with daily use. They are often prescribed empirically, often in high doses and with many patients being treated with multiple PPIs without an objective diagnosis. Therefore, they are believed to be overprescribed and used without indication. In this article we discuss the appropriate clinical indications for PPIs, review in detail the major associated adverse events, and put in perspective key issues in balancing benefits and risk of this exceptional (and safe) class of drug.
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Affiliation(s)
- Felice Schnoll-Sussman
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA
| | - Rachel Niec
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA
| | - Philip O Katz
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, 1315 York Avenue, New York City, NY 10021, USA.
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31
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Guedes JVM, Aquino JA, Castro TLB, Augusto de Morais F, Baldoni AO, Belo VS, Otoni A. Omeprazole use and risk of chronic kidney disease evolution. PLoS One 2020; 15:e0229344. [PMID: 32130255 PMCID: PMC7055824 DOI: 10.1371/journal.pone.0229344] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 02/04/2020] [Indexed: 12/26/2022] Open
Abstract
RATIONALE, AIMS AND OBJECTIVES In recent years, the use of proton pump inhibitors (PPI), especially omeprazole, has been associated with development of chronic kidney disease (CKD). These drugs are widely used worldwide. Although some studies have found an association between the use of PPI and the onset of acute renal failure and CKD. This study aims to analyze the association between the continuous use of omeprazole and the progression of CKD in adult and elderly individuals. METHOD A retrospective cohort study was conducted with patients followed up at a nephrology clinic in Brazil, in 2016 and 2017. Information about clinical and sociodemographic data, health behaviors, and medication use were collected from all patients diagnosed with CKD through consultation of medical charts and the Brazilian health information system (SIS). The participants were allocated into two groups: users and non-users of omeprazole, and the progression of CKD was then evaluated for each group. In the bivariate analysis, the Mann-Whitney U test to compare the quantitative variables between groups, and the Pearson/Fisher two-tailed chi-square test to compare the categorical variables were applied. Multivariate analysis was performed using Cox regression. RESULTS A total of 199 CKD patients were attended in the polyclinic, and of these, 42.7% were omeprazole users. There was a higher percentage of CKD progression in users (70.6%) compared to non-users (10.5%). The hazard ratio was 7.34 (CI: 3.94-13.71), indicating a higher risk of progression to worse stages of CKD in omeprazole users than in non-users. As for the other variables, no statistically significant difference was found between groups (p > 0.05). CONCLUSION An association between omeprazole use and progression of CKD stage was identified, showing a higher risk of disease evolution among omeprazole users.
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Affiliation(s)
- João Victor Marques Guedes
- Department of Health Sciences, Federal University of São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil
| | - Jéssica Azevedo Aquino
- Department of Health Sciences, Federal University of São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil
| | | | - Flávio Augusto de Morais
- Department of Nephrology, Ambulatory of Municipal Polyclinic of Divinopolis, Divinópolis, Minas Gerais, Brazil
| | - André Oliveira Baldoni
- Department of Health Sciences, Federal University of São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil
| | - Vinícius Silva Belo
- Department of Health Sciences, Federal University of São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil
| | - Alba Otoni
- Department of Health Sciences, Federal University of São João Del-Rei (UFSJ), Divinópolis, Minas Gerais, Brazil
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Kosedo I, Tokushige A, Takumi T, Yoshikawa A, Teraguchi K, Takenouchi K, Shiraishi K, Ikeda D, Imamura M, Sonoda T, Kanda D, Ikeda Y, Ido A, Ohishi M. Use of proton pump inhibitors is associated with an increase in adverse cardiovascular events in patients with hemodialysis: Insight from the kids registry. Eur J Intern Med 2020; 72:79-87. [PMID: 31735546 DOI: 10.1016/j.ejim.2019.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 10/04/2019] [Accepted: 11/06/2019] [Indexed: 12/27/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are known to increase the risk of mortality and cardiovascular events in the general population. However, in patients with maintenance hemodialysis, PPI effects are under investigated. METHODS We analyzed the risk of PPIs for cardiovascular events using the Kagoshima Dialysis (KIDS) registry, a prospective, multicenter, observational study in patients with maintenance hemodialysis in Japan. RESULTS In all, 531 patients were enrolled from June 2015 to December 2018. One-year follow-up data were available for 376 patients (Use of PPIs at baseline (PPI group): 217 patients and without PPIs (No PPI group): 159 patients). The incidence of a composite outcome (all-cause mortality, non-fatal myocardial infarction, or non-fatal stroke) was higher in patients in the PPI group than the No PPI group (15.2% vs. 4.4%; hazard ratio (HR): 3.65, 95% confidence interval (CI): 1.61-8.23, P = 0.002). In the multivariate analysis, even after adjustment for covariates, the use of PPIs was an independent risk factor for a composite outcome (HR: 2.38, 95% CI: 1.02-5.54, P = 0.045). We performed propensity score matching analysis as a sensitivity analysis, showing a consistent result. The incidence of bleeding showed no difference between the two groups (15.7% vs. 11.3%; HR: 1.46, 95% CI: 0.83-2.59, P = 0.19). CONCLUSIONS These results indicate that the use of PPIs in patients with maintenance hemodialysis might increase mortality and cardiovascular events without decreasing the risk of bleeding. Therefore, it should always be analyzed if a patient truly needs PPIs.
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Affiliation(s)
- Ippei Kosedo
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Akihiro Tokushige
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
| | - Takuro Takumi
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | | | | | | | | | | | | | - Takeshi Sonoda
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Daisuke Kanda
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Yoshiyuki Ikeda
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Akio Ido
- Department of Digestive and Lifestyle Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Mitsuru Ohishi
- Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Prevention and Analysis of Cardiovascular Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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Hussain S, Singh A, Zameer S, Jamali MC, Baxi H, Rahman SO, Alam M, Altamish M, Singh AK, Anil D, Hussain MS, Ahmad A, Najmi AK. No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis. J Gastroenterol Hepatol 2020; 35:19-28. [PMID: 31334885 DOI: 10.1111/jgh.14789] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 06/30/2019] [Accepted: 07/16/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.
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Affiliation(s)
- Salman Hussain
- Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Ambrish Singh
- Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
| | - Saima Zameer
- Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Mohammad Chand Jamali
- Department of Health and Medical Sciences, Khawarizmi International College, Abu Dhabi, United Arab Emirates
| | - Harveen Baxi
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Syed Obaidur Rahman
- Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Mahtab Alam
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Mohammad Altamish
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Avinash Kumar Singh
- Department of Pharmaceutical Medicine (Division of Pharmacology), School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | | | - Md Sarfaraj Hussain
- Institute of Pharmaceutical Sciences, Sanskriti University, Mathura, Uttar Pradesh, India
| | - Adil Ahmad
- Department of Pharmacognosy, Jamia Hamdard, New Delhi, India
| | - Abul Kalam Najmi
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
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Abstract
A substantial volume of literature exists linking proton pump inhibitor (PPI) use with a multitude of serious adverse events. There is uncertainty, however, over whether these associations are clinically important. Excessive concern about PPI-related adverse events may leave patients at risk of harm by leaving acid-related upper gastrointestinal disease untreated. Conversely, the risk of treatments may outweigh the benefits if any of the purported adverse events are directly caused by PPI use; this is of particular concern where indications for PPI use are not present. In this paper, we review the studies which have reported associations between adverse events and PPI use, discuss the proposed mechanisms of action, grade the confidence in whether these associations are truly causal, and provide advice regarding balancing the benefits of PPI use against their possible harms.
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Affiliation(s)
- Evan Elias
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada
| | - Laura E Targownik
- Section of Gastroenterology, Department of Internal Medicine, Rady School of Medicine, University of Manitoba, 805G-715 McDermot Avenue, Winnipeg, MB, R3E 3P4, Canada.
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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: 75] [Impact Index Per Article: 12.5] [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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Cardiovascular and non-cardiovascular concerns with proton pump inhibitors: Are they safe? Trends Cardiovasc Med 2019; 29:353-360. [DOI: 10.1016/j.tcm.2018.10.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 10/09/2018] [Accepted: 10/16/2018] [Indexed: 12/11/2022]
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Tuppin P, Rivière S, Deutsch D, Gastaldi-Menager C, Sabaté JM. Burden of drug use for gastrointestinal symptoms and functional gastrointestinal disorders in France: a national study using reimbursement data for 57 million inhabitants. Therap Adv Gastroenterol 2019; 12:1756284819853790. [PMID: 31320929 PMCID: PMC6628544 DOI: 10.1177/1756284819853790] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 05/08/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Gastrointestinal therapeutic drugs (GTDs) are extensively prescribed. The aim of this study was to investigate the characteristics of GTD use in a large population: the French general health scheme beneficiaries (87% of the 66 million inhabitants) in 2016. METHODS The national health data system was used to identify individual characteristics, diseases and GTD classes reimbursed, together with the costs, using anatomical therapeutic chemical class. RESULTS Among the 57.5 million individuals included, 45% received at least one reimbursement among the 130 million prescriptions reimbursed (90% prescribed by a general practitioner): proton-pump inhibitors (PPI; A02BC: 24%), drugs for functional gastrointestinal disorders (A03: 20%), drugs for constipation (A06: 10%), antidiarrheals, intestinal anti-inflammatory/anti-infective agents (A07: 10%), antiemetics and antinauseants (A04: 7%), other drugs for acid-related disorders (A02X: 6%), other drugs for peptic ulcer and gastro-oesophageal reflux disease (A02BX: 4.5%), antacids (A02A: 1.5%). The overall cost of reimbursed GTDs was €707 million and the mean cost per user was €28. Marked variations were observed according to age, sex, and disease. The rates of at least one reimbursement among infants were A07: 28%, A03: 17%, A02BX: 9%, A02X: 7%, A02BC: 6% and A06: 5%. Women more frequently received a reimbursement than men for each GTD class. Reimbursement rates also varied according to health status (end-stage renal disease A02BC: 66%, pregnancy A03: 53%, A04: 11%), treatments (people with at least six reimbursements for nonsteroidal anti-inflammatory drugs in 2016 A02BC: 62%). Chronic GTD use (>10 reimbursements/year) was observed in 19% of people with at least one A02BC reimbursement, A02BX: 11%, A03: 7%, A04: 2%, A06: 17% and A07: 3%. CONCLUSIONS This study demonstrates extensive and chronic use of GTD in France, raising the question of their relevance according to current guidelines. They must be disseminated to general practitioners, who are the main prescribers of these drugs.
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Affiliation(s)
| | | | - David Deutsch
- Service de Gastroentérologie Hôpital Avicenne,
AP-HP, Bobigny, France
| | | | - Jean-Marc Sabaté
- Service de Gastroentérologie Hôpital Avicenne,
AP-HP, Bobigny, France INSERM U-987, Physiopathologie et Pharmacologie
Clinique de la Douleur, Hôpital Ambroise Paré, Boulogne-Billancourt,
France
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Desbuissons G, Mercadal L. Is red meat consumption the confounding factor explaining the association between chronic kidney disease and proton pump inhibitors? Nephrol Ther 2019; 15:191-192. [DOI: 10.1016/j.nephro.2018.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 11/28/2018] [Indexed: 10/26/2022]
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Ribiere S, Guillaumot MA, Barré A, Abou Ali E, Barret M, Chaussade S, Coriat R. Quel est le VRAI risque au long cours des inhibiteurs de la pompe à protons ? Presse Med 2019; 48:503-510. [PMID: 30926204 DOI: 10.1016/j.lpm.2019.02.011] [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: 01/29/2019] [Accepted: 02/11/2019] [Indexed: 11/30/2022] Open
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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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Analysis of postmarketing safety data for proton-pump inhibitors reveals increased propensity for renal injury, electrolyte abnormalities, and nephrolithiasis. Sci Rep 2019; 9:2282. [PMID: 30783195 PMCID: PMC6381091 DOI: 10.1038/s41598-019-39335-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 01/18/2019] [Indexed: 12/13/2022] Open
Abstract
Proton pump inhibitors, PPIs, are widely prescribed and sold globally. Although initially intended for time-limited treatment of acute disorders, such as gastric ulcers and esophagitis, PPIs are now commonly used for prolonged durations and are considered safe for over the counter access. Recent studies have raised concern over associations between PPI use and acute kidney injury, chronic kidney disease, end-stage renal disease, and electrolyte abnormalities. The growing concern over potentially serious adverse drug reactions warrants an evaluation of post marketing surveillance data. In this study of over ten million FDA Adverse Event Reporting System records, we provided evidence of kidney injury and electrolyte imbalances in an alarming number of patients taking PPIs. Additionally, we assessed differences between specific PPIs and observed significant electrolyte and renal abnormalities for each individual drug with varying magnitudes.
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The association of proton pump inhibitors and chronic kidney disease: cause or confounding? Curr Opin Nephrol Hypertens 2019; 27:182-187. [PMID: 29432214 DOI: 10.1097/mnh.0000000000000406] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW To discuss whether the recently described relationship between proton pump inhibitor (PPI) use and the risk of adverse kidney outcomes represents a causal relationship or is merely the result of confounding. RECENT FINDINGS A wave of observational studies has described an association between PPI use and the risk of development of chronic kidney disease and its progression to end-stage renal disease. The results are generally robust and remarkably consistent across different studies. The application of modern pharmacoepidemiologic methods to estimate the effect of a putative unmeasured or unknown confounder or set of confounders on the relationship of PPI use and risk of adverse renal outcomes suggests that confounding is unlikely to explain away the reported association. SUMMARY The constellation of evidence from all available studies suggests that PPI use is associated with increased risk of adverse kidney outcomes. Exercising vigilance in the use of PPI is warranted.
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Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf 2018; 10:2042098618809927. [PMID: 31019676 PMCID: PMC6463334 DOI: 10.1177/2042098618809927] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 09/28/2018] [Indexed: 12/17/2022] Open
Abstract
Proton pump inhibitors (PPIs) are among the most frequently prescribed
medications. Their use is likely even higher than estimated due to an increase
in the number of PPIs available without a prescription. Appropriate indications
for PPI use include Helicobacter pylori infection, erosive
esophagitis, gastric ulcers, and stress ulcer prevention in high-risk critically
ill patients. Unfortunately, PPIs are often used off-label for extended periods
of time. This increase in PPI usage over the past two decades has called into
question the long-term effects of these medications. The association between PPI
use and infection, particularly Clostridium difficile and
pneumonia, has been the subject of several studies. It’s proposed that
the alteration in gastrointestinal microflora by PPIs produces an environment
conducive to development of these types of infections. At least one study has
suggested that long-term PPI use increases the risk of dementia. Drug
interactions are an important and often overlooked consideration when
prescribing any medication. The potential interaction between PPIs and
antiplatelet agents has been the subject of multiple studies. One of the more
recent concerns with PPI use is their role in the development or progression of
chronic kidney disease. There is also some literature suggesting that PPIs
contribute to the development of various micronutrient deficiencies. Most of the
literature examining the potential adverse effects of PPI use is composed of
retrospective, observation studies. There is a need for higher quality studies
exploring this relationship.
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Affiliation(s)
- Megan Jaynes
- Division of Critical Care, Department of Pharmacy, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Avinash B Kumar
- Division of Critical Care, Department of Anesthesiology, Vanderbilt University, Nashville, TN 37212, USA
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Abstract
PURPOSE OF REVIEW The present review summarizes the past year's literature, both clinical and basic science, regarding potential adverse effects of proton pump inhibitors. RECENT FINDINGS Proton pump inhibitors are amongst the most widely prescribed and overprescribed medications worldwide. Although generally considered well tolerated, epidemiologic studies mining large databases have reported a panoply of purported serious adverse effects associated with proton pump inhibitors, including chronic kidney disease, cognitive decline, myocardial infarction, stroke, bone fracture and even death. It should be noted that the quality of the evidence underlying these associations is very low and these studies, by design, cannot ascribe cause and effect. Nonetheless, these associations have been sensationalized in the media and misinterpreted by patients and providers. Unintended consequences of the fake news are that patients are not being prescribed and/or taking clinical guideline-recommended proton pump inhibitors to prevent and treat complications from gastroesophageal reflux disease and upper gastrointestinal bleeding precipitated by NSAIDs and dual antiplatelet therapies. In addition, physicians, who already have limited time to interact with their patients, are spending an inordinate amount of additional time placing these findings into proper perspective and reassuring their patients when initiating treatment as well as on every follow-up visit. SUMMARY Most of the recent highly publicized serious adverse effects ascribed to proton pump inhibitors are not based on demonstrable evidence. Nevertheless, when proton pump inhibitors are prescribed long-term, they should be used at the lowest effective dose and the need for their use periodically reassessed.
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Locatelli F, Del Vecchio L, Ponticelli C. Should we really STOP treating patients with IgA nephropathy with steroids? Physiol Int 2018; 105:101-109. [PMID: 29975121 DOI: 10.1556/2060.105.2018.2.10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis all over the world. Once considered as a benign disease, today the scientific community is aware that a significant percentage of patients eventually progress to end-stage kidney disease (ESKD). The rate of progression is often very slow. Since 1980s, several therapeutic attempts have been made with steroids. Despite different molecules, doses, and lengths of treatment, the majority of uncontrolled and controlled studies found benefits in terms of proteinuria reduction and reduction of the risk of ESKD. This was obtained with reasonable safety and tolerability, especially when steroids are given at relatively low dose and for a period not exceeding 6 months. Recently, two randomized controlled trials have questioned the efficacy and safety of steroid therapy in IgAN. However, these trials have many drawbacks that are to be considered when interpreting the findings.
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Affiliation(s)
- F Locatelli
- 1 Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, ASST Lecco , Lecco, Italy
| | - L Del Vecchio
- 1 Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, ASST Lecco , Lecco, Italy
| | - C Ponticelli
- 2 Department of Nephrology and Dialysis, Ospedale Maggiore Policlinico , Milan, Italy
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Haastrup PF, Thompson W, Søndergaard J, Jarbøl DE. Side Effects of Long-Term Proton Pump Inhibitor Use: A Review. Basic Clin Pharmacol Toxicol 2018; 123:114-121. [PMID: 29658189 DOI: 10.1111/bcpt.13023] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Accepted: 04/05/2018] [Indexed: 12/13/2022]
Abstract
Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have been raised. Therefore, side effects are important to be aware of and several suggested side effects of long-term use have been studied. In this MiniReview, we sum up the evidence of side effects related to long-term PPI treatment. Suspected side effects are mainly related to increased susceptibility to infections, secondary hypergastrinaemia, impeded absorption of micronutrients or idiosyncratic reactions. Most of the potential side effects have only been evaluated in observational studies demonstrating conflicting and weak associations with a substantial risk of confounding. However, a high probability of causality seems to be established for the side effects increased risk of gastrointestinal infections and rebound acid hypersecretion following discontinuation of treatment due to secondary hypergastrinaemia. The risk of side effects should not be a reason to withhold PPIs from patients with a true indication, and worry about poorly proven side effects should not lead to unnecessary discontinuation. The most important safety issue regarding PPI therapy is to critically evaluate the indication when initiating treatment and reconsidering the indication in long-term-treated patients.
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Affiliation(s)
- Peter Fentz Haastrup
- Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense C, Denmark
| | - Wade Thompson
- Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense C, Denmark
| | - Jens Søndergaard
- Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense C, Denmark
| | - Dorte Ejg Jarbøl
- Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense C, Denmark
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Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, Holland L, Wilson K, Bhala N, Hawkey C, Hochberg M, Hunt R, Laine L, Lanas A, Patrono C, Baigent C. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol 2018; 3:231-241. [PMID: 29475806 PMCID: PMC5842491 DOI: 10.1016/s2468-1253(18)30037-2] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 01/05/2018] [Accepted: 01/08/2018] [Indexed: 12/13/2022]
Abstract
Background Gastroprotectant drugs are used for the prevention and treatment of peptic ulcer disease and might reduce its associated complications, but reliable estimates of the effects of gastroprotectants in different clinical settings are scarce. We aimed to examine the effects of proton-pump inhibitors (PPIs), prostaglandin analogues, and histamine-2 receptor antagonists (H2RAs) in different clinical circumstances by doing meta-analyses of tabular data from all relevant unconfounded randomised trials of gastroprotectant drugs. Methods We searched MEDLINE and Embase from Jan 1, 1950, to Dec 31, 2015, to identify unconfounded, randomised trials of a gastroprotectant drug (defined as a PPI, prostaglandin analogue, or H2RA) versus control, or versus another gastroprotectant. Two independent researchers reviewed the search results and extracted the prespecified outcomes and key characteristics for each trial. We did meta-analyses of the effects of gastroprotectant drugs on ulcer development, bleeding, and mortality overall, according to the class of gastroprotectant, and according to the individual drug within a gastroprotectant class. Findings We identified comparisons of gastroprotectant versus control in 849 trials (142 485 participants): 580 prevention trials (110 626 participants), 233 healing trials (24 033 participants), and 36 trials for the treatment of acute upper gastrointestinal bleeding (7826 participants). Comparisons of one gastroprotectant drug versus another were available in 345 trials (64 905 participants), comprising 160 prevention trials (32 959 participants), 167 healing trials (28 306 participants), and 18 trials for treatment of acute upper gastrointestinal bleeding (3640 participants). The median number of patients in each trial was 78 (IQR 44·0–210·5) and the median duration was 1·4 months (0·9–2·8). In prevention trials, gastroprotectant drugs reduced development of endoscopic ulcers (odds ratio [OR] 0·27, 95% CI 0·25–0·29; p<0·0001), symptomatic ulcers (0·25, 0·22–0·29; p<0·0001), and upper gastrointestinal bleeding (0·40, 0·32–0·50; p<0·0001), but did not significantly reduce mortality (0·85, 0·69–1·04; p=0·11). Larger proportional reductions in upper gastrointestinal bleeding were observed for PPIs than for other gastroprotectant drugs (PPIs 0·21, 99% CI 0·12–0·36; prostaglandin analogues 0·63, 0·35–1·12; H2RAs 0·49, 0·30–0·80; phet=0·0005). Gastroprotectant drugs were effective in preventing bleeding irrespective of the use of non-steroidal anti-inflammatory drugs (phet=0·56). In healing trials, gastroprotectants increased endoscopic ulcer healing (3·49, 95% CI 3·28–3·72; p<0·0001), with PPIs more effective (5·22, 99% CI 4·00–6·80) than prostaglandin analogues (2·27, 1·91–2·70) and H2RAs (3·80, 3·44–4·20; phet<0·0001). In trials among patients with acute bleeding, gastroprotectants reduced further bleeding (OR 0·68, 95% CI 0·60–0·78; p<0·0001), blood transfusion (0·75, 0·65–0·88; p=0·0003), further endoscopic intervention (0·56, 0·45–0·70; p<0·0001), and surgery (0·72, 0·61–0·84; p<0·0001), but did not significantly reduce mortality (OR 0·90, 0·72–1·11; p=0·31). PPIs had larger protective effects than did H2RAs for further bleeding (phet=0·0107) and blood transfusion (phet=0·0130). Interpretation Gastroprotectants, in particular PPIs, reduce the risk of peptic ulcer disease and its complications and promote healing of peptic ulcers in a wide range of clinical circumstances. However, this meta-analysis might have overestimated the benefits owing to small study bias. Funding UK Medical Research Council and the British Heart Foundation.
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Affiliation(s)
- Benjamin Scally
- Emergency Department, Glasgow Royal Infirmary, Glasgow, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Jonathan R Emberson
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, Oxford, UK
| | - Enti Spata
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, Oxford, UK
| | - Christina Reith
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Kelly Davies
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Heather Halls
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Lisa Holland
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Kate Wilson
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Oxford, UK
| | - Neeraj Bhala
- Gastroenterology and Liver Unit, Queen Elizabeth Hospital, Mindelsohn Way, Birmingham, UK; Institute of Applied Health Research, University of Birmingham, Edgbaston, UK
| | - Christopher Hawkey
- Nottingham Digestive Diseases Centre, Queen's Medical Centre, Nottingham, UK
| | - Marc Hochberg
- Department of Medicine and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Richard Hunt
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University Health Science Centre, Hamilton, ON, Canada
| | - Loren Laine
- Section of Digestive Diseases, Yale School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA
| | - Angel Lanas
- Service of Digestive Diseases, University Clinic Hospital, University of Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain
| | - Carlo Patrono
- Department of Pharmacology, Catholic University School of Medicine, Rome, Italy
| | - Colin Baigent
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, Oxford, UK.
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