The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study

Douwes, Rianne M.; Gomes-Neto, António W; Eisenga, Michele F.; Loon, Elisabet Van; Schutten, Joëlle C; Gans, Rijk O. B.; Naesens, Maarten; Berg, Else van den; Sprangers, Ben; Berger, Stefan P.; Navis, Gerjan; Blokzijl, Hans; Meijers, Björn; Bakker, Stephan J. L.; Kuypers, Dirk

doi:10.1371/journal.pmed.1003140

Cited by 10 publications

(10 citation statements)

References 67 publications

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“…Xie and colleagues showed a small excess of cause specific mortality due to cardiovascular disease, chronic kidney, disease, and upper gastrointestinal cancer in patients taking PPIs [25]. In addition, another cohort study determined increased risk of overall mortality with PPI use in kidney transplant recipients with average eGFR of 52 [26]. These findings are in contrast with the results from Grant's study which looked at the CKD population specifically and found no association between PPI use and increased mortality.…”

Section: Discussionmentioning

confidence: 90%

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

et al. 2021

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Background The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. Methods Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk. Results 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71). Conclusions Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

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Section: Discussionmentioning

confidence: 90%

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

et al. 2021

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“…The comparable rates of mortality and graft loss are other important points to be considered. Higher rate of mortality was reported in PPIs‐treated patients among transplant and non‐transplant population in some studies 25,28,29 ; therefore, this result should be interpreted with caution and should be evaluated in further studies with a higher population number. PPIs use is associated with development of acute and chronic kidney damage with several mechanisms such as recurrent acute interstitial nephritis or endothelial dysfunction 8 …”

Section: Discussionmentioning

confidence: 76%

“…Our updated meta‐analysis of PPIs versus H2RAs confirmed these results. One large cohort study demonstrated that PPIs use is associated with a dose‐dependent, increased mortality risk in KTRs independent of potential confounders compared with non‐PPIs users 29 ; however, that study did not mention the rate of H2RAs users among patients in non‐PPIs user group. Other potential short‐ and long‐term adverse effects of the acid‐suppressive therapies, especially PPIs, are fracture risk, 4,8 hypomagnesemia 23,31 and risk of Clostridioides difficile infection.…”

Section: Discussionmentioning

confidence: 98%

“…9 Our updated meta-analysis of PPIs versus H2RAs confirmed these results. One large cohort study demonstrated that PPIs use is associated with a dose-dependent, increased mortality risk in KTRs independent of potential confounders compared with non-PPIs users 29 ; however, that study did not mention the rate of H2RAs users among Our results indicated the comparable rates of patient and graft loss, osteoporosis or fracture, Clostridioides difficile infection, and pneumonia between the two groups, while a non-significant higher rate of hypomagnesemia and/or need for magnesium supplementation was seen in PPIs-exposed KTRs. Hypomagnesemia has been recognized as a side effect of PPIs with various mechanisms such as the reduced gastrointestinal absorption of magnesium.…”

Section: Discussionmentioning

confidence: 99%

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Comparing safety of proton‐pump inhibitors versus H2‐receptor antagonists in kidney transplant recipients: A systematic review and meta‐analysis

Mohammadi

Yaribash

Razi

et al. 2021

Clinical Pharmacy Therapeu

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What is known and objective: Multiple studies have been conducted to compare the safety of proton-pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) as acidsuppressive treatment in kidney transplant recipients with conflicting results. This systematic review and meta-analysis aimed to evaluate the risk of adverse effects in kidney transplant patients receiving PPIs compared to those treated with H2RAs. Methods:A systematic search was performed on the databases from inception to June 2021. The treatment effects were expressed as odds ratio (OR), weighted mean differences (WMD) and their 95% confidence intervals (CI) and pooled by a randomeffects model. Results and Discussions:Eight studies, consisting 4,844 patients, were included.

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“…This is, however, not standard policy in transplant centers worldwide, probably because of an absence of scientific data and guideline recommendation that support the routine use of PPIs post‐transplant. Added to this, previous studies performed among chronic kidney disease (CKD) populations and transplant populations show that PPI use is associated with a higher risk of hypomagnesaemia, acute kidney injury, incident CKD, CKD progression and even premature mortality [ 27 , 28 ]. Although the evidence for these adverse effects mainly comes from observational studies, it does emphasize the need to avoid unnecessary use of PPIs after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Type of proton‐pump inhibitor and risk of iron deficiency in kidney transplant recipients – results from the TransplantLines Biobank and Cohort Study

et al. 2021

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Proton-pump inhibitors (PPIs) have been associated with iron deficiency (ID) in kidney transplant recipients (KTRs). Gastric acid plays a pivotal role in the intestinal absorption of non-heme iron, but the pharmacodynamics of PPIs differs in potency of acid suppression. We hypothesized that the risk of ID might be lower in KTRs using a less potent PPI. In a cohort of 724 KTRs from the TransplantLines Biobank and Cohort Study (NCT03272841), PPI use was associated with ID [odds ratio (OR) 2.02; 95% CI 1.36-2.98]. Compared with no PPI use, the point estimate of the odds ratio for risk of ID for pantoprazole (OR 1.55; 95%CI 0.78-3.10) was lower than for esomeprazole and omeprazole (3.58; 95%CI 1.73-7.40 and 1.96; 95%CI 1.31-2.94, respectively). When comparing pantoprazole users with omeprazole users on an equipotent dose (≤20 omeprazole equivalents (OE)/day) omeprazole, but not pantoprazole was associated with ID, although the lack of a significant effect of pantoprazole on the risk of ID could be caused by a lack of power. Furthermore, risk of ID was higher among users of a high PPI dose (≥ 20 OE/day) and OE as continuous variable was also independently associated with ID, indicating that risk of ID is higher while using a more potent PPI. Further investigation seems warranted to confirm whether pantoprazole leads to less ID in KTRs.

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The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study

Abstract: Background Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs.

Cited by 10 publications

References 67 publications

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression

Comparing safety of proton‐pump inhibitors versus H2‐receptor antagonists in kidney transplant recipients: A systematic review and meta‐analysis

Type of proton‐pump inhibitor and risk of iron deficiency in kidney transplant recipients – results from the TransplantLines Biobank and Cohort Study

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