Chronic Use of Proton-Pump Inhibitors and Iron Status in Renal Transplant Recipients.
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SUBMITTER: Douwes RM
PROVIDER: S-EPMC6780301 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundKidney transplant recipients are commonly prescribed proton-pump inhibitors (PPIs), but due to concern for polypharmacy, chronic use should be limited.ObjectiveThe objective was to describe PPI use in kidney transplant recipients beyond their first year of transplant to better inform and support deprescribing initiatives.DesignWe conducted a retrospective, population-based cohort study using linked health care databases.SettingThis study was conducted in Alberta, Canada.PatientsWe included all prevalent adult, kidney-only transplant recipients between April 2008 and December 2017 who received their transplant between May 2002 and December 2017.MeasurementsThe primary outcome was ongoing or new PPI use and patterns of use, including frequency and duration of therapy, and assessment of indication for PPI use.MethodsWe ascertained baseline characteristics, covariate information, and outcome data from the Alberta Kidney Disease Network (AKDN). We compared recipients with evidence of a PPI prescription in the 3 months prior to study entry to those with a histamine-2-receptor antagonist (H2Ra) fill and those with neither.ResultsWe identified 1823 kidney transplant recipients, of whom 868 (48%) were on a PPI, 215 (12%) were on an H2Ra, and 740 (41%) were on neither at baseline. Over a median follow-up of 5.4 years (interquartile range [IQR] = 2.6-9.3), there were almost 45 000 unique PPI prescriptions dispensed, the majority (80%) of which were filled by initial PPI users. Recipients who were on a PPI at baseline would spend 91% (IQR = 70-98) of their graft survival time on a PPI in follow-up, and nephrologists were the main prescribers. We identified an indication for ongoing PPI use in 54% of recipients with the most common indication being concurrent antiplatelet use (26%).LimitationsOur kidney transplant recipients have access to universal health care coverage which may limit generalizability. We identified common gastrointestinal indications for PPI use but did not include rare conditions due to concerns about the validity of diagnostic codes. In addition, symptoms suggestive of reflux may not be well coded as the focus of follow-up visits is more likely to focus on kidney transplant.ConclusionsMany kidney transplant recipients are prescribed a PPI at, or beyond, the 1-year post-transplant date and are likely to stay on a PPI in follow-up. Almost half of the recipients in our study did not have an identifiable indication for ongoing PPI use. Nephrologists frequently prescribe PPIs to kidney transplant recipients and should be involved in deprescribing initiatives to reduce polypharmacy.
| S-EPMC10865938 | biostudies-literature
Project description:Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: -0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: -0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43-3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32-4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.
| S-EPMC6947083 | biostudies-literature
Project description:Hepcidin is a small peptide with a critical role in cellular iron homeostasis, as it regulates utilization of stored iron and antimicrobial defense in inflammation (bacterial and fungal). Since it was isolated in 2000, and especially in the last decade, numerous studies aimed to evaluate the clinical use of plasma and urine hepcidin as a marker of anemia, especially anemia of chronic disease and post-transplant anemia (PTA). Hepcidin regulation is delicately tuned by two inflammatory pathways activated by interleukin-6 (IL-6) and bone morphogenic proteins (BMPs) and iron regulated pathway sensitive to circulating transferin-iron (TR-Fe) complex. BMP-mediated pathway and TR-Fe sensitive pathway seem to be connected by hemojuveline, a BMP co-factor that interacts with transferine receptor 2 (TRF2) in cases of high TR-Fe circulatory concentration. In addition to these regulatory mechanisms other regulators and signaling pathways are being extensively researched. ?Hepcidin has been identified as an important contributor to morbidity and mortality in end stage renal disease (ESRD) but no such association has jet been found in case of PTA. However, there is an association between higher doses of erythropoiesis-stimulating agents (ESA) and mortality in the posttransplant period and the assumption that hepcidin might play a role in ESA resistance in PTA. Thus the review's main goal was to summarize papers published on the association of hepcidin with PTA, give up-to-date information on hepcidin regulation and on potential therapeutics that optimize hepcidin regulation. We also compared the performances of tests for hepcidin determination and reviewed research on immunosuppressants' (IS) effect on hepcidin concentration.
| S-EPMC4783088 | biostudies-other
Project description:IntroductionImmune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients.Patients and methodsWe performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis.ResultsA total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis.ConclusionIn addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.
| S-EPMC9701615 | biostudies-literature
Project description:Transplant recipients receive potent immunosuppressive drugs in order to prevent graft rejection. Therapeutic drug monitoring is the current approach to guide the dosing of calcineurin inhibitors, mammalian target of rapamycin inhibitors (mTORi) and mofetil mycophenolate. Target concentrations used in pediatric patients are extrapolated from adult studies. Gene polymorphisms in metabolizing enzymes and drug transporters such as cytochromes CYP3A4 and CYP3A5, UDP-glucuronosyl transferase, and P-glycoprotein are known to influence the pharmacokinetics and dose requirements of immunosuppressants. The implications of pharmacogenomics in this patient population is discussed. Genetic information can help with achieving target concentrations in the early post-transplant period, avoiding adverse drug reactions and drug-drug interactions. Evidence about genetic studies and transplant outcomes is revised.
| S-EPMC4332348 | biostudies-literature
Project description:To evaluate the characteristics of the prescription of the proton pump inhibitor drugs (PPI) and the adherence to the indications of the guidelines regulating the reimbursement limitations set forth by the Italian Drug Agency.Thirty general practitioners (GP) participated in the study, providing data on more than 40000 patients in total. The population was divided into non occasional users of PPI drugs (PPI users) and non-users (PPI non-users) based on evidence of a prescription of at least 3 packs of PPIs in the last 90 d before analysis. The data provided allowed an assessment of compliance with the requirements of eligibility for PPI reimbursement according to the Italian Drug Agency rules, in order to obtain subpopulations which complied or not with the rules.Six thousand three hundred and twenty-two patients were found to be PPI users, accounting for 14.9% of the patient population. PPI users were more frequently female, older and more frequently diagnosed with gastroesophageal reflux disease, gastric or duodenal ulcers, arthropathy, heart disease and cancer than the rest of the population. PPI users had more frequently received prescriptions for non-steroidal ant-inflammatory drugs (NSAIDS), acetylsalicylic acid (ASA), oral anticoagulant therapy (OAT) and systemic steroids. PPI reimbursement resulted applicable to 69.3% of the PPI users, but a potential for reimbursement of PPI prescriptions was identified in the non PPI users for the treatment of peptic or reflux disease (8.5%) and for the protection of gastric damage caused by NSAIDS (6.1%). Patients who are potentially eligible for reimbursement are older, diagnosed with arthropathy and heart disease more frequently and most commonly receive NSAID and ASA prescriptions compared with PPI users who do not satisfy eligibility requirements. Patients in whom it was not possible to identify conditions related to prescription suitability were more frequently associated with use of OAT.A substantial number of patients who apparently do not meet prescription suitability conditions can be identified, but among non PPI users on the contrary, it is possible to identify an equal number of patients for whom prescription would be suitable. Poor suitability can be identified in the population receiving OAT. Thus, there is scope for decreasing inappropriate use of PPI drugs by adhering to certain criteria and by involving all interested parties.
| S-EPMC5547376 | biostudies-other
Project description:Proton-pump inhibitors (PPIs) have been associated with iron deficiency (ID) in kidney transplant recipients (KTRs). Gastric acid plays a pivotal role in the intestinal absorption of non-heme iron, but the pharmacodynamics of PPIs differs in potency of acid suppression. We hypothesized that the risk of ID might be lower in KTRs using a less potent PPI. In a cohort of 724 KTRs from the TransplantLines Biobank and Cohort Study (NCT03272841), PPI use was associated with ID [odds ratio (OR) 2.02; 95% CI 1.36-2.98]. Compared with no PPI use, the point estimate of the odds ratio for risk of ID for pantoprazole (OR 1.55; 95%CI 0.78-3.10) was lower than for esomeprazole and omeprazole (3.58; 95%CI 1.73-7.40 and 1.96; 95%CI 1.31-2.94, respectively). When comparing pantoprazole users with omeprazole users on an equipotent dose (≤20 omeprazole equivalents (OE)/day) omeprazole, but not pantoprazole was associated with ID, although the lack of a significant effect of pantoprazole on the risk of ID could be caused by a lack of power. Furthermore, risk of ID was higher among users of a high PPI dose (≥ 20 OE/day) and OE as continuous variable was also independently associated with ID, indicating that risk of ID is higher while using a more potent PPI. Further investigation seems warranted to confirm whether pantoprazole leads to less ID in KTRs.
| S-EPMC9293430 | biostudies-literature
Project description:Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.
| S-EPMC6913203 | biostudies-literature
Project description:BackgroundProton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients.ObjectiveWe aimed to determine the net impact of PPIs on hospital mortality among medical inpatients.DesignA microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality.ParticipantsSimulated general medical inpatients outside the intensive care unit (ICU).Main measureChange in overall mortality during hospitalization.Key resultsNew initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios.ConclusionsFor the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.
| S-EPMC4803704 | biostudies-literature
Project description:BackgroundStatins achieve potent LDL lowering in the general population leading to a significant cardiovascular (CV) risk reduction. In renal transplant recipients (RTR) statins are included in treatment guidelines, however, conclusive evidence of improved cardiovascular outcomes has not been uniformly provided and concerns have been raised about simultaneous use of statins and the immunosuppressant cyclosporine. This study aimed to elucidate the effect of statins on a compound CV endpoint, comprised of ischaemic CV events and CV mortality in RTR, with subgroup analysis focussing on cyclosporine users.Method622 included RTR (follow-up 5.4 years) were matched based on propensity scores and dichotomized by statin use. Survival analysis was conducted.ResultsCox regression showed that statin use was not significantly associated with the compound CV endpoint in a fully adjusted model (HR = 0.81, 95% CI = 0.53-1.24, P = .33). Subgroup analyses in RTR using cyclosporine revealed a strong positive association of statin use with the CV compound outcome in a fully adjusted model (HR = 6.60, 95% CI 1.75-24.9, P = .005). Furthermore, statin use was positively correlated with cyclosporine trough levels (correlation coefficient 0.11, P = .04).ConclusionIn conclusion, statin use does not significantly decrease incident CV events in an overall RTR cohort, but is independently associated with CV-specific mortality and events in cyclosporine using RTR, possibly due to a bilateral pharmacological interaction.
| S-EPMC8596424 | biostudies-literature