Acid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis

Qiu, Tingting; Zhou, Junwen; Zhang, Chao

doi:10.1111/jgh.14157

Cited by 27 publications

(31 citation statements)

References 59 publications

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“…In recent years, the adverse effects of PPIs on the kidney have received increasing attention worldwide. Studies have shown that PPIs can increase the risk of AKI, acute interstitial nephritis (AIN), CKD, and end-stage renal disease [21, 22]. PPIs (mainly omeprazole) were the most common drugs that cause drug-induced AIN in the elderly in the US [23, 24].…”

Section: Discussionmentioning

confidence: 99%

Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Liu¹,

Yan²,

Wang³

et al. 2020

Kidney Dis

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Introduction: Drug-induced acute kidney injury (D-AKI) is one of the important types of AKI. The incidence of D-AKI in China has rarely been studied. Objective: This study aims to explore the disease burden, related drugs, and risk factors of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in China. Suspected AKI was screened based on serum creatinine changes in accordance with the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI, patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. Suspected AKI was firstly evaluated for the possibility of D-AKI by pharmacists using the Naranjo Scale and finally defined as D-AKI by nephrologists through reviewing AKI clinical features. Results: Altogether 280,255 hospitalized patients were screened and 1,960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as having D-AKI (37.50%, 735/1,960) with an in-hospital mortality rate of 13.88% and 54.34% of the survivors did not achieve full renal recovery. 1,642 drugs were related to AKI in these patients. Anti-infectives, diuretics, and proton pump inhibitors were the top 3 types of drugs relevant to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitute, and carbapenem related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Conclusion: In China, D-AKI has caused a substantial medical burden. Efforts should be made to pursue nephrotoxic drug stewardship to minimize attributable risk and improve the prevention, diagnosis, and treatment of D-AKI.

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Section: Discussionmentioning

confidence: 99%

Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Liu¹,

Yan²,

Wang³

et al. 2020

Kidney Dis

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“…Nevertheless, the list of potential side-effects related to long-term PPI use is increasing, including among others, chronic kidney disease, osteoporosis and fractures, Clostridium difficile infections, community acquired pneumonia, cardiac diseases, and even increased mortality [8][9][10][11][12][13][14][15][16][17][18][19]. An increasing number of studies have also investigated the risk of cancer with most evidence existing for gastric, colorectal and pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

2019

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Background The long-term safety of proton pump inhibitors (PPIs) is increasingly questioned. The aim of our study was to assess the risk of pancreatic cancer among longterm PPI users in Sweden. Methods This population-based nationwide Swedish cohort study including 796,492 adult long-term PPI users has been used to calculate the standardized incidence rate ratios (SIRs) and 95% confidence intervals (CI) for pancreatic cancer, stratifying by indications of use, age, sex, and duration of use. The risk among all 20,210 long-term H2-receptor antagonist users was assessed as comparison.Results Pancreatic cancer was found in 1733 long-term PPI users, and 25 H2-receptor antagonist users. For PPI users, the risk of pancreatic cancer was increased overall (SIRs = 2.22; 95% CI 2.12-2.32) and in all subgroup analyses, with the highest risk among PPI-users younger than 40 years (SIR = 8.90,, and among individuals with a history of Helicobacter pylori (SIR = 2.99, 95% CI 2.54-3.49). After the first year after enrolment (during which PPI use may be because of early symptoms of pancreatic cancer), the risk remained increased over time, with SIR = 1.57 (95% CI 1.38-1.76) after 5 years. No associations were found for H2-receptor antagonists (SIR = 1.02, 95% CI 0.66-1.51). Conclusions This large study showed an increased risk of pancreatic cancer in long-term users of PPIs in Sweden, in particular among the youngest users.

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“…Other possible mechanisms include inhibition of the lysosomal proton pump, with decreased nitric oxide synthesis and increased generation of superoxide anion, or hypomagnesemia, which could lead to increased secretion of inflammatory and atherogenic markers. Proton pump inhibitors were shown to be associated with adverse kidney outcomes; however, a recent systematic review noted that this evidence was of low or insufficient quality . Therefore, additional studies evaluating the relationship between PPI use and renal disease are necessary, especially considering the increasing global use of PPIs, because this relationship could pose a substantial disease and financial burden to health care systems.…”

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confidence: 99%

Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study

et al. 2019

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BACKGROUND Proton pump inhibitors (PPIs) have been linked to acute kidney injury (AKI) and chronic kidney disease (CKD); however, current evidence has only been evaluated in a small number of studies with short follow-up periods. This study examined the association between PPI use and risk of incident AKI and CKD in a large population-based health maintenance organization (HMO) cohort. METHODS Patients aged 18 years or older, without evidence of preexisting renal disease, started on PPI therapy, and those continuously enrolled for at least 12 months between July 1993 and September 2008 were identified in an HMO database. Incidences of AKI and CKD were defined using documented International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes or a glomerular filtration rate less than 60 ml/min/1.73 m 2 after initiation of PPI therapy. Patients with AKI were followed for up to 90 days (cohort 1), and patients with CKD required at least 1 year of follow-up (cohort 2). Multivariable logistic regression analyses were used to adjust for differences in demographics (excluding race), comorbidities, and medication use between groups. RESULTS In 93,335 patients in the AKI cohort, 16,593 of whom were exposed to PPIs, the incidence rate of AKI was higher in the PPI group than nonusers (36.4 vs 3.54 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPI exposure was associated with an increased risk of AKI (adjusted odds ratio [aOR] 4.35, 95% confidence interval [CI] 3.14-6.04, p<0.0001). In 84,600 patients in the CKD cohort, 14,514 of whom were exposed to PPIs, the incidence rate of CKD was higher in the PPI group than nonusers (34.3 vs 8.75 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPIs were associated with a higher risk of CKD compared with controls (aOR 1.20, 95% CI 1.12-1.28, p<0.0001). Associations between PPI use and AKI and CKD persisted in propensity score-matched analyses. CONCLUSION The use of PPIs is associated with an increased risk of incident AKI and CKD. This relationship could have a considerable public health impact; therefore, health care provider education and deprescribing initiatives will be necessary to raise awareness and reduce health care burden. KEY WORDS acute kidney injury, chronic kidney disease, observational study, proton pump inhibitors.

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Acid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis

Abstract: Proton pump inhibitor therapy significantly increased the risks of acute interstitial nephritis, AKI, CKD, and ESRD. Similar risks were not identified for H RA therapy. More clinical trials are needed to confirm our findings.

Cited by 27 publications

References 59 publications

Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Drug-Induced Hospital-Acquired Acute Kidney Injury in China: A Multicenter Cross-Sectional Survey

Long-term proton pump inhibitor usage and the association with pancreatic cancer in Sweden

Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study

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