Incidence, Pathogenesis, and Management of Proton Pump Inhibitor-Induced Nephrotoxicity

Wei, Xiao; Wang, Yuanyuan; Xu, Zhaopeng; Wang, Chun; Wu, Yingliang

doi:10.1007/s40264-022-01181-4

Cited by 9 publications

(4 citation statements)

References 73 publications

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“…These variabilities of PKs in first‐generation PPIs are likely to be relevant to our results, and suggest that CYP2C19 PM is associated with increased kidney injury by lansoprazole, which is likely due to the high exposure level of lansoprazole. The pathogenic mechanism of PPI‐related renal injury has not been fully elucidated, but is suspected to involve specific immune‐mediated responses or changes in the gut microbiota 17,28 . This study showed that, in patients treated with lansoprazole, CYP2C19 PM was associated with a significantly shorter time to occurrence of a 30% decrease in eGFR.…”

Section: Discussionmentioning

confidence: 78%

“…The pathogenic mechanism of PPI-related renal injury has not been fully elucidated, but is suspected to involve specific immune-mediated responses or changes in the gut microbiota. 17,28 This study showed that, in patients treated with lansoprazole, CYP2C19 PM was associated with a significantly shorter time to occurrence of a 30% decrease in eGFR. The variability in PK and PD parameters of lansoprazole is likely to contribute to its efficacy and toxicity, and renal injury may result from the accumulation of unmetabolized lansoprazole.…”

Section: Discussionmentioning

confidence: 81%

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Relationships of Proton Pump Inhibitor‐Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study

Fukui,

Noda,

Ikeda

et al. 2024

Clin Pharma and Therapeutics

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Proton pump inhibitors (PPIs) have recently been reported to be linked with nephrotoxicity. PPIs are metabolized mainly or partly by cytochrome P450 2C19 (CYP2C19). However, the relationship between CYP2C19 genetic polymorphism and PPI‐induced nephrotoxicity is unclear. In this study, we aimed to analyze the association between the time of occurrence of renal injury by PPIs, including lansoprazole, esomeprazole, rabeprazole, and vonoprazan, and CYP2C19 metabolizer status classified by CYP2C19 genotypes. Patients prescribed PPIs were reviewed in this retrospective cohort study. The primary outcome was the time to a 30% decrease in estimated glomerular filtration rate (eGFR) from baseline. In patients treated with lansoprazole, the time to a 30% decrease in eGFR for the CYP2C19 poor metabolizer (PM) group was significantly shorter than that for the non‐PM group (hazard ratio for PM vs. non‐PM, 2.43, 95% confidence interval, 1.21 to 4.87, P = 0.012). In contrast, in patients that received esomeprazole, rabeprazole, or vonoprazan, no significant differences were found in the time to a 30% decrease in eGFR between non‐PM and PM groups. The adjusted hazard ratios for the time to a 30% eGFR decrease in patients treated with lansoprazole were significantly higher for CYP2C19 PM, hypertension, and a history of myocardial infarction. In conclusion, this retrospective study showed that CYP2C19 metabolizer status was associated with the time to a 30% eGFR decrease in patients treated with lansoprazole, but not with esomeprazole, rabeprazole, or vonoprazan.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 81%

Relationships of Proton Pump Inhibitor‐Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study

Fukui,

Noda,

Ikeda

et al. 2024

Clin Pharma and Therapeutics

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“…PPIs also increase the risk of acute interstitial nephritis; the specific mechanism is unknown, although it is thought to be linked to immune-mediated responses, oxidative stress, and possibly renal tubular death. 30 , 31 The nephrotoxic effect of these drugs is especially exacerbated when they are administered frequently in large doses to patients who have underlying medical conditions and complications such as dehydration and sepsis. Nephrotoxic drugs are the most common risk factors for HAAKI in medical patients, unlike surgical patients as reported in another study as well.…”

Section: Discussionmentioning

confidence: 99%

Hospital-Acquired Acute Kidney Injury in Non-Critical Medical Patients in a Developing Country Tertiary Hospital: Incidence and Predictors

Mekonnen,

Leulseged,

Hassen

et al. 2024

IJNRD

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Background Acute kidney injury (AKI) is a frequent complication in critical patients, leading to a worse prognosis. Although its consequences are worse among critical patients, AKI is also associated with less favorable outcomes in non-critical patients. Therefore, understanding the magnitude of the problem in these patients is crucial, yet there is a scarcity of evidence in non-critical settings, especially in resource limited countries. Hence, the study aimed at determining the incidence and predictors of hospital acquired acute kidney injury (HAAKI) in non-critical medical patients who were admitted at a large tertiary hospital in Ethiopia. Methods A retrospective chart review study was conducted from September 25, 2022 to January 20, 2023 among 232 hospitalized non-critical medical patients admitted to St. Paul’s Hospital Millennium Medical College between January 2020 and January 2022. The incidence of HAAKI was estimated using incidence density per total person day (PD) observation of the study participants. To identify predictors of HAAKI, a log binomial regression model was fitted at a p value of ≤0.05. The magnitude of association was measured using adjusted relative risk (ARR) with its 95% CI. Results During the median follow-up duration of 11 days (IQR, 6–19 days), the incidence of HAAKI was estimated to be 6.0 per 100 PD (95% CI = 5.5 to 7.2). Significant predictors of HAAKI were found to be having type 2 diabetes mellitus (ARR = 2.36, 95% CI = 1.03, 5.39, p-value=0.042), and taking vancomycin (ARR = 3.04, 95% CI = 1.38, 6.72, p-value=0.006) and proton pump inhibitors (ARR = 3.80, 95% CI = 1.34,10.82, p-value=0.012). Conclusion HAAKI is a common complication in hospitalized non-critical medical patients, and is associated with a common medical condition and commonly prescribed medications. Therefore, it is important to remain vigilant in the prevention and timely identification of these cases and to establish a system of rational prescribing habits.

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“…Studies have shown that vancomycin causes acute kidney injury through several mechanisms, the most well-known of which being oxidative stress in the kidney’s proximal tubules. PPIs also increase the risk of acute interstitial nephritis; the specific mechanism is unknown, although it is thought to be linked to immune-mediated responses, oxidative stress, and possibly renal tubular death (30, 31). The nephrotoxic effect of these drugs is especially exacerbated when they are administered frequently in large doses to patients who have underlying medical conditions and complications such as dehydration and sepsis.…”

Section: Discussionmentioning

confidence: 99%

Hospital-Acquired Acute Kidney Injury in Non-critical Medical Patients in a Developing Country Tertiary Hospital: Incidence and Predictors

Mekonnen,

Leulseged,

Hassen

et al. 2023

Preprint

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Background: Acute kidney injury (AKI) is a frequent complication in critical patients leading to worse prognosis. Although the consequences of AKI are worse among critical patients, AKI is also associated with less favorable outcomes in non-critical patients. Hence, understanding the magnitude of the problem in these patients is crucial, yet there is a scarcity of evidence in non-critical settings, especially in resource limited countries. Hence, the study aimed at determining the incidence and predictors of hospital acquired acute kidney injury (HAAKI) in non-critical medical patients who were admitted at a large tertiary hospital in Ethiopia. Methods: A retrospective chart review study was conducted among 232 hospitalized non-critical medical patients admitted to St. Paul's Hospital Millennium Medical College between January 2020 and January 2022. Data was characterized using frequency and median with interquartile range. To identify predictors of HAAKI, a log binomial regression model was fitted at a p value of ≤ 0.05. The magnitude of association was measured using adjusted relative risk (ARR) with its 95% CI. Results: During the median follow-up duration of 11 days (IQR, 6-19 days), the incidence of HAAKI was estimated to be 6.0 per 100 person-day observation (95% CI= 5.5 to 7.2). Significant predictors of HAAKI were found to be having type 2 diabetes mellitus (ARR=2.36, 95% CI= 1.03, 5.39, p-value=0.042), and taking vancomycin (ARR=3.04, 95% CI= 1.38, 6.72, p-value=0.006) and proton pump inhibitors (ARR=3.80, 95% CI = 1.34,10.82, p-value=0.012). Conclusions: HAAKI is a common complication in hospitalized non-critical medical patients, and is associated with a common medical condition and commonly prescribed medications. Therefore, it is important to remain vigilant in the prevention and timely identification of these cases and to establish a system of rational prescribing habits.

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Incidence, Pathogenesis, and Management of Proton Pump Inhibitor-Induced Nephrotoxicity

Cited by 9 publications

References 73 publications

Relationships of Proton Pump Inhibitor‐Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study

Relationships of Proton Pump Inhibitor‐Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study

Hospital-Acquired Acute Kidney Injury in Non-Critical Medical Patients in a Developing Country Tertiary Hospital: Incidence and Predictors

Hospital-Acquired Acute Kidney Injury in Non-critical Medical Patients in a Developing Country Tertiary Hospital: Incidence and Predictors

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