Proton pump inhibitors and acute interstitial nephritis: Report and analysis of 15 cases

Simpson, Ian; Marshall, Mark R.; Pilmore, Helen; Manley, Paul; Williams, Laurie C.; Thein, Hla-Hla; Voss, David

doi:10.1111/j.1440-1797.2006.00651.x

Cited by 136 publications

(114 citation statements)

References 12 publications

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“…It is known that they can cause dark-colored urine, interstitial nephritis, urinary tract infection and frequent urination (20)(21)(22), but to the best of our knowledge and available data, this is the first report of a possible association between urinary incontinence and treatment with PPIs. The underlying mechanism remains unexplained.…”

Section: Discussionmentioning

confidence: 94%

Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

2017

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Ključne besede:gastroezofagealna refluksna bolezen; otrok; inhibitorji protonske črpalke; H2-blokatorji; eozinofilni ezofagitis; na inhibitor protonske črpalke odzivna ezofagealna eozinofilija Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report Klinični primer razvoja urinske inkontinence pri 7-letnem fantu med zdravljenjem z inhibitorjem protonske črpalke in izginotje kliničnopatoloških znakov eozinofilnega ezofagitisa po zdravljenju z antagonisti H2 receptorjev AbstractBackground: Several diseases result in profound infiltration of esophageal mucosa by eosinophilic granulocites, with gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE) and proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE) being the most prevalent. Proton-pump-inhibitor-responsive esophageal eosinophilia (PPI-REE) is a newly recognized entity that must be differentiated from eosinophilic esophagitis (EoE).Case presentation: A 7-year old Slovenian male presented with a few-month history of chest pain, regurgitation and heartburn. First endoscopy was performed and revealed pronounced longitudinal furrows, and on hystology examination > 70 eosinophils per high power field were found through the entire thickness of epithelium and in the submucosis with eosinophilic microabscess formation. Results of 24-hour pH-monitoring (without impedance monitoring) excluded pathologic acid reflux. All allergy tests were negative. The patient started treatment with proton pump inhibitors (PPIs) for three times, twice with pantoprazole before the endoscopy and once with esomeprasole after it to exclude the diagnosis of GERD and PPI-REE. Urinary incontinence reappeared each time just few days after starting treatment and disapeared few days after stopping it. Therefore, urinary incontinence was considered as a plausible adverse effect of therapy with PPIs. As treatment with PPIs was not tolerated, a therapy with H2-receptor antagonists ranitidine was applied for more than 2 months followed by a second endoscopy. Both symptoms and esophageal eosinophilia completely resolved with ranitidine. The resolution of esophageal eosinophilia in PPI-REE has been atributed to proton pump independent antiinflammatory effects of PPIs. No such effects have been described in H2-receptor antagonists. Conclusions:Two unique phenomena were observed in the pediatric patient with profound esophageal eosinophilia: urinary incontinence as an adverse effect of therapy with PPIs, and complete resolution of esophageal eosinophilic inflammation with typical features of EoE after treatment with H2-receptor antagonists. IzvlečekIzhodišča: Mnoge bolezni lahko privedejo do obsežne infiltracije sluznice požiralnika z eozinofilnimi granulociti. Med njimi so najbolj pogoste gastroezofagealna refluksna bolezen, eozinofilni ezofagitis in na inhibitor protonske črpalke odzivna ezofag...

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Section: Discussionmentioning

confidence: 94%

Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

2017

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“…In New Zealand, omeprazole, the most widely used PPI, was shown to be associated in AIN in older patients. Some individuals were exposed to the medication for up to 18 months prior to the onset of AIN and others developed AIN after a doubling in dose [1]. This raised the question of whether direct drug toxicity contributed to the development of interstitial inflammation.…”

Section: Introductionmentioning

confidence: 99%

Omeprazole‐induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype

Helsby¹,

Lo²,

Simpson³

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Omeprazole‐induced acute interstitial nephritis (OIAIN) is a rare adverse drug reaction. It is typically considered to be an idiosyncratic reaction affecting elderly patients. Omeprazole is a substrate for CYP2C19 and individuals who are homozygous variant for the null allele are poor metabolizers of this drug. These individuals have higher exposure to omeprazole. In the elderly metabolism of omeprazole is reported to be decreased despite a ‘normal activity’ genotype. WHAT THIS PAPER ADDS • The CYP2C19 poor metabolizer genotype was not over represented in patients with OIAIN. However, almost a third of the patients appeared to have deficient CYP2C19 function. • Metabolism of omeprazole may be compromised in the elderly and caution should be exercised when using this medication in this group of patients. AIM Omeprazole‐induced acute interstitial nephritis (OIAIN) is a rare adverse event. It is unknown if this is an idiosyncratic immune mediated reaction or if it relates to direct drug toxicity. Individuals who are homozygous for the variant alleles of CYP2C19 are poor metabolizers of omeprazole and have a greater exposure to the drug. The aim of this study was to determine the prevalence of the CYP2C19 poor metabolizer genotype and phenotype in patients with OIAIN. METHODS Twenty patients were genotyped for the CYP2C19 variant alleles (*2, 681G>A and *3, 636G>A) by RFLP‐PCR analysis and eighteen phenotyped for CYP2C19 metabolizer status. RESULTS The frequency of the CYP2C19*2 allelic variant was 12.5%, no *3 allelic variants were detected and no patient was a homozygous variant genotype. This was not different from the expected frequency. 33% of subjects were phenotypically CYP2C19 poor metabolizers. CONCLUSIONS There was discordance between CYP2C19 genotype and phenotype. However, up to 45% of healthy elderly subjects have a poor metabolizer phenotype. Thus neither CYP2C19 poor metabolizer genotype nor phenotype is a risk factor for OIAIN.

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“…95 Although many drugs can result in AIN, PPI-induced AIN requires special mention because it is one of the most common causes of AIN in some regions. 96 Since PPIs are widely prescribed drugs, the incidence of PPI-induced AIN is on the rise. As with most cases of drug-induced AIN, withdrawal of the drug usually results in recovery.…”

Section: Proton-pump Inhibitorsmentioning

confidence: 99%

Drug-induced impairment of renal function

Pazhayattil¹,

Shirali²

2014

IJNRD

117

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Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies.

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Proton pump inhibitors and acute interstitial nephritis: Report and analysis of 15 cases

Cited by 136 publications

References 12 publications

Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

Development of urinary incontinence in a 7-year old boy after therapy with proton pump inhibitors and complete resolution of his clinicopathologic features of eosinophilic esophagitis after H2-receptor antagonist treatment: A case report

Omeprazole‐induced acute interstitial nephritis is not related to CYP2C19 genotype or CYP2C19 phenotype

Drug-induced impairment of renal function

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