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Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

ABSTRACT: Over the last decades, proton pump inhibitors (PPIs) have been widely used as the mainstay for treatment and prevention of gastrointestinal side effects, gastroesophageal reflux, and peptic ulcer disease. However, their safety profile has come into question recently after reports relating them to several side effects as well as kidney disease. Omeprazole, one of the mainly used PPIs, is almost entirely metabolized by the liver but the resulting metabolites are renally excreted. These metabolites may inhibit cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) reversibly, but as recent evidence suggests, they may also be involved in causing kidney disease. In the setting of renal dysfunction, these metabolites will not be excreted from the body and will accumulate further causing kidney damage and inhibiting CYP enzymes to a greater extent. Abnormally high serum prolactin levels leading to galactorrhea may be the result of such an accumulation. To our knowledge, there have been only three previously reported cases of PPI-induced galactorrhea in the literature but none in a kidney transplant recipient. In patients with established kidney disease and reduced glomerular filtration rate like kidney transplant recipients, the use of PPIs should be thoroughly assessed. Reduced clearance of their metabolites may lead to progression of the kidney disease and lead to more unwanted side effects. We present a case of a female kidney transplant recipient with worsening allograft function who presented with sudden galactorrhea and hyperprolactinemia while on a high-dose omeprazole for gastroesophageal reflux disease.

SUBMITTER: Prikis M

PROVIDER: S-EPMC7254079 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

Prikis Marios M MacDougall Julie J Narasimhadevara Nina N

Case reports in transplantation 20200513

Over the last decades, proton pump inhibitors (PPIs) have been widely used as the mainstay for treatment and prevention of gastrointestinal side effects, gastroesophageal reflux, and peptic ulcer disease. However, their safety profile has come into question recently after reports relating them to several side effects as well as kidney disease. Omeprazole, one of the mainly used PPIs, is almost entirely metabolized by the liver but the resulting metabolites are renally excreted. These metabolites ...[more]

PMID: 32566351

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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.

Project description:BackgroundEsophageal eosinophilia can be proton pump inhibitor (PPI) resistant or responsive, representing 2 entities known as eosinophilic esophagitis (EoE) and PPI-responsive esophageal eosinophilia (PPI-REE), respectively. Although they present with similar clinical features, EoE is accepted to be an antigen-driven, TH2-associated allergic disorder, whereas the cause of PPI-REE remains a mystery.ObjectiveIn this study, our aim was to investigate the pathogenesis of PPI-REE by using a recently described EoE diagnostic panel (EDP) composed of a set of 94 esophageal transcripts and to determine whether PPI therapy reverses any esophageal transcriptional abnormalities.MethodsWe evaluated the EDP signature in biopsy samples obtained from adult and pediatric patients with PPI-REE from 4 institutions and compared the pre- and post-PPI therapy expression profiles of these subjects with those of patients with active EoE.ResultsThe EDP differentiated patients with EoE from control subjects with 100% accuracy among the 4 clinical sites. Bioinformatics analysis revealed largely overlapping transcriptomes between patients with PPI-REE and those with EoE, including the genes for eosinophil chemotaxis (eotaxin 3, CCL26), barrier molecules (desmoglein 1, DSG1), tissue remodeling (periostin, POSTN), and mast cells (carboxypeptidase A, CPA3). PPI monotherapy alone almost completely reversed the allergic inflammatory transcriptome of patients with PPI-REE. Furthermore, we identified a set of candidate genes to differentiate patients with EoE from those with PPI-REE before treatment.ConclusionThese findings provide definitive evidence that PPI-REE is a disease entity with significant molecular overlap with EoE, suggesting that many patients with PPI-REE represent a continuum of the same pathogenic allergic mechanisms that underlie EoE and thus might constitute a subphenotype of patients with EoE. The ability of PPI therapy to nearly entirely reverse gene expression associated with PPI-REE, particularly that associated with classic features of allergic inflammation, provides new insight into potential disease etiology and management strategies for patients with significant esophageal eosinophilia.

Project description:Rationale & objectiveKidney function can be adversely affected by significant tricuspid regurgitation (TR) owing to effects on cardiac output and systemic venous congestion. However, the impact of significant TR on short- and long-term kidney function following a kidney transplant remains uncertain.Study designRetrospective observational cohort.Setting & participantsKidney transplant recipients from a single center between 2016 and 2019.ExposureSignificant TR, defined by at least moderate regurgitation, on echocardiogram before kidney transplantation.OutcomesPrimary end points included the estimated glomerular filtration rate (eGFR) at the following 3 time points: 2 weeks, 3 months, and 1 year after transplantation. Secondary end points included major adverse cardiac events including nonfatal myocardial infarction, all-cause mortality, and hospitalization owing to cardiovascular disease.Analytical approachPropensity score matching was performed in 1:3 ratio between patients treated with significant TR and controls, within a caliper 0.05 standard deviation of the propensity score, to analyze for the primary end point.ResultsAmong 557 kidney transplant recipients, 26 (5%) exhibited significant TR pretransplantation. According to propensity score matching analysis, with 1:3 ratio between 24 patients with significant TR and 72 controls, the presence of significant TR was associated with a lower eGFR posttransplantation. Specifically, the mean eGFR was 41.2 mL/min/1.73 m2 compared to 53.3 mL/min/1.73 m2 at 2 weeks (P < 0.01), 50.0 mL/min/1.73 m2 versus 60.3 mL/min/1.73 m2 at 3 months (P < 0.01), and 49.4 mL/min/1.73 m2 versus 61.2 mL/min/1.73 m2 at 1 year (P < 0.01). Delayed graft function was observed in 41.7% of the patients with significant TR compared to 12.5% of those without significant TR (P < 0.01). No patients with significant TR required dialysis after 1 year. 1-year major adverse cardiac events were nonsignificantly higher among patients with significant TR (20.8% vs 8.1%; P = 0.16).LimitationsRetrospective design and relatively small TR population.ConclusionsThe presence of significant TR among kidney transplant recipients was associated with a lower eGFR at 2 weeks, 3 months, and 1 year following transplant, although all remained dialysis independent at 1 year.

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Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

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Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

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