Publication

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

Douwes, R. M., Gomes-Neto, A. W., Eisenga, M. F., Van Loon, E., Schutten, J. C., Gans, R. O. B., Naesens, M., van den Berg, E., Sprangers, B., Berger, S. P., Navis, G., Blokzijl, H., Meijers, B., Bakker, S. J. L. & Kuypers, D., 15-Jun-2020, In : PLOS MEDICINE. 17, 6, 19 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Douwes, R. M., Gomes-Neto, A. W., Eisenga, M. F., Van Loon, E., Schutten, J. C., Gans, R. O. B., ... Kuypers, D. (2020). The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study. PLOS MEDICINE, 17(6). https://doi.org/10.1371/journal.pmed.1003140

Author

Douwes, Rianne M ; Gomes-Neto, António W ; Eisenga, Michele F ; Van Loon, Elisabet ; Schutten, Joëlle C ; Gans, Rijk O B ; Naesens, Maarten ; van den Berg, Else ; Sprangers, Ben ; Berger, Stefan P ; Navis, Gerjan ; Blokzijl, Hans ; Meijers, Björn ; Bakker, Stephan J L ; Kuypers, Dirk. / The association between use of proton-pump inhibitors and excess mortality after kidney transplantation : A cohort study. In: PLOS MEDICINE. 2020 ; Vol. 17, No. 6.

Harvard

Douwes, RM, Gomes-Neto, AW, Eisenga, MF, Van Loon, E, Schutten, JC, Gans, ROB, Naesens, M, van den Berg, E, Sprangers, B, Berger, SP, Navis, G, Blokzijl, H, Meijers, B, Bakker, SJL & Kuypers, D 2020, 'The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study', PLOS MEDICINE, vol. 17, no. 6. https://doi.org/10.1371/journal.pmed.1003140

Standard

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; Van Loon, Elisabet; Schutten, Joëlle C; Gans, Rijk O B; Naesens, Maarten; van den Berg, Else; Sprangers, Ben; Berger, Stefan P; Navis, Gerjan; Blokzijl, Hans; Meijers, Björn; Bakker, Stephan J L; Kuypers, Dirk.

In: PLOS MEDICINE, Vol. 17, No. 6, 15.06.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Douwes RM, Gomes-Neto AW, Eisenga MF, Van Loon E, Schutten JC, Gans ROB et al. The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study. PLOS MEDICINE. 2020 Jun 15;17(6). https://doi.org/10.1371/journal.pmed.1003140


BibTeX

@article{f55337be6824419dadcf3a92fd560f99,
title = "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.METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57{\%} were male, and 56.6{\%} used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95{\%} CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95{\%} CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95{\%} CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95{\%} CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.",
author = "Douwes, {Rianne M} and Gomes-Neto, {Ant{\'o}nio W} and Eisenga, {Michele F} and {Van Loon}, Elisabet and Schutten, {Jo{\"e}lle C} and Gans, {Rijk O B} and Maarten Naesens and {van den Berg}, Else and Ben Sprangers and Berger, {Stefan P} and Gerjan Navis and Hans Blokzijl and Bj{\"o}rn Meijers and Bakker, {Stephan J L} and Dirk Kuypers",
year = "2020",
month = "6",
day = "15",
doi = "10.1371/journal.pmed.1003140",
language = "English",
volume = "17",
journal = "PLOS MEDICINE",
issn = "1549-1277",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "6",

}

RIS

TY - JOUR

T1 - The association between use of proton-pump inhibitors and excess mortality after kidney transplantation

T2 - A cohort study

AU - Douwes, Rianne M

AU - Gomes-Neto, António W

AU - Eisenga, Michele F

AU - Van Loon, Elisabet

AU - Schutten, Joëlle C

AU - Gans, Rijk O B

AU - Naesens, Maarten

AU - van den Berg, Else

AU - Sprangers, Ben

AU - Berger, Stefan P

AU - Navis, Gerjan

AU - Blokzijl, Hans

AU - Meijers, Björn

AU - Bakker, Stephan J L

AU - Kuypers, Dirk

PY - 2020/6/15

Y1 - 2020/6/15

N2 - 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.METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.

AB - 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.METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation.CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.

U2 - 10.1371/journal.pmed.1003140

DO - 10.1371/journal.pmed.1003140

M3 - Article

C2 - 32542023

VL - 17

JO - PLOS MEDICINE

JF - PLOS MEDICINE

SN - 1549-1277

IS - 6

ER -

ID: 127965659