Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease

Lazarus, Benjamin; Yuan, Chen; Wilson, F. Perry; Sang, Yingying; Chang, Alexander R.; Coresh, Josef

doi:10.1001/jamainternmed.2015.7193

Cited by 598 publications

(575 citation statements)

References 30 publications

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“…Additionally, there was a dose response association with increased doses of PPI and CKD. The association was replicated in another independent cohort from Geisinger Health system [84]. In addition to the association with CKD, PPI use has been associated with acute kidney injury (AKI).…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 88%

“…A recent analysis of patients from the Atherosclerosis Risk in Communities study (N = 10,439) who were followed for 13.9 years found that the prevalence of CKD is 50% higher in patients who used PPI compared to nonusers [84]. This association remained significant after performing a propensity-adjusted analysis.…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…While many of these epidemiological studies did not evaluate the influence of PPI dose, most of studies that evaluated doses, have shown that the documented risks are increased with higher PPI doses [84,89,94,96]. While these large epidemiological studies do not provide insight into the risk relative of CYP2C19 genotype, given that there does appear to be a link between dose and risk, it is plausible that these PPI-related adverse events are linked to higher exposure to PPIs in patients with CYP2C19 PM/IM phenotype versus NM or RM/UM phenotypes.…”

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

“…However, recent epidemiological studies have suggested this may not be the case, with a number of serious adverse outcomes linked to PPI use. Importantly some of these studies document a link between the risk under study and prolonged duration or dose [84,89,94], suggesting that increased drug concentrations may increase the risk of PPI associated adverse events. If this is the case, there may also be a link between CYP2C19 PM genotype and PPI associated risks as a result of increased drug concentrations.…”

Section: Expert Opinionsmentioning

confidence: 99%

See 3 more Smart Citations

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

189

172

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Introduction: Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism.Areas covered: This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism. Additionally, the role of CYP2C19 genetic variability in the therapeutic effectiveness or outcomes of PPI therapy is highlighted in details, to provide supporting evidence for the potential value of CYP2C19 genotype-guided approaches to PPI drug therapy.Expert opinion: There is a large body of evidence describing the impact of CYP2C19 variability on PPIs and its potential role in individualizing PPI therapy, yet, CYP2C19 pharmacogenetics has not been widely implemented into clinical practice. More data are needed but CYP2C19 genotype-guided dosing of PPIs is likely to become increasingly common and is expected to improve clinical outcomes, and minimize side effects related to PPIs.

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Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 88%

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Section: Cyp2c19 and Ppi Pharmacogeneticsmentioning

confidence: 99%

Section: Expert Opinionsmentioning

confidence: 99%

See 2 more Smart Citations

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Rouby

Lima

Johnson

2018

Expert Opinion on Drug Metabolism & Toxicology

189

172

View full text Add to dashboard Cite

show abstract

“…PPIs have been associated with negative side effects such as hypomagnesemia, hypocalcemia, hypoparathyroidism, chronic kidney disease, end-stage renal disease, hip fracture, community-acquired pneumonia, Clostridium difficile infection, and increased risk of SIBO (small intestinal bacterial overgrowth) [9,[22][23][24][25]. Millions of prescriptions are written and filled each year for antacids, H2 blockers, and PPIs [6].…”

Section: Discussionmentioning

confidence: 99%

Using Probiotics Instead of Pharmaceuticals to Treat Gastrointestinal Disorders

Rowles¹

2017

J Clin Gastroenterol Hepatol

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Chronic Kidney Disease Diagnosis and Management

Chen

Knicely

Grams

2019

JAMA

Self Cite

1,152

658

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hronic kidney disease (CKD) affects between 8% and 16% of the population worldwide and is often underrecognized by patients and clinicians. [1][2][3][4] Defined by a glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m 2 , albuminuria of at least 30 mg per 24 hours, or markers of kidney damage (eg, hematuria or structural abnormalities such as polycystic or dysplastic kidneys) persisting for more than 3 months, 5 CKD is more prevalent in low-and middle-income than in highincome countries. 6 Globally, CKD is most commonly attributed to diabetes and/or hypertension, but other causes such as glomerulonephritis, infection, and environmental exposures (such as air pollution, herbal remedies, and pesticides) are common in Asia, sub-Saharan Africa, and many developing countries. 4 Genetic risk factors may also contribute to CKD risk. For example, sickle cell trait and the presence of 2 APOL1 risk alleles, both common in people of African ancestry but not European ancestry, may double the risk of CKD. 4,[7][8][9][10] In the United States, the average rate of GFR decline is approximately 1 mL/min/1.73 m 2 per year in the general pop-ulation, 11,12 and the lifetime risk of developing a GFR of less than 60 mL/min/1.73 m 2 is more than 50%. 13 Early detection and treatment by primary care clinicians is important because progressive CKD is associated with adverse clinical outcomes, including endstage kidney disease (ESKD), cardiovascular disease, and increased mortality. [14][15][16][17] Recent professional guidelines suggest a risk-based approach to the evaluation and management of CKD. 5,[18][19][20] This review includes discussion of new calculators for determining risk of CKD progression that may be useful in clinical practice (eg, https://kidneyfailurerisk.com/) and focuses on the diagnosis, evaluation, and management of CKD for primary care clinicians. Considerations for referral to a nephrologist and dialysis initiation are also covered. MethodsA literature search to April 2019 was conducted using Medline and PubMed with search terms including CKD, chronic renal failure, IMPORTANCE Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death.OBSERVATIONS Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate [GFR] <60 mL/min/1.73 m 2 or albuminuria Ն30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular ...

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Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease

Cited by 598 publications

References 30 publications

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

Using Probiotics Instead of Pharmaceuticals to Treat Gastrointestinal Disorders

Chronic Kidney Disease Diagnosis and Management

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