TY - JOUR
T1 - Risk of Potentially Inappropriate Medications in Adults With CKD
T2 - Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study
AU - CRIC Study Investigators
AU - Hall, Rasheeda K.
AU - Blumenthal, Jacob B.
AU - Doerfler, Rebecca M.
AU - Chen, Jing
AU - Diamantidis, Clarissa J.
AU - Jaar, Bernard G.
AU - Kusek, John W.
AU - Kallem, Krishna
AU - Leonard, Mary B.
AU - Navaneethan, Sankar D.
AU - Sha, Daohang
AU - Sondheimer, James H.
AU - Wagner, Lee Ann
AU - Yang, Wei
AU - Zhan, Min
AU - Fink, Jeffrey C.
AU - Appel, Lawrence J.
AU - Feldman, Harold I.
AU - Go, Alan S.
AU - Rahman, Mahboob
AU - Rao, Panduranga S.
AU - Shah, Vallabh O.
AU - Townsend, Raymond R.
AU - Unruh, Mark L.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health (NIH) under Award Number K76AG059930 (to RH) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under Award Number R01DK090008 (to JCF). This study was also supported by the ASN Foundation for Kidney Research (to RH) and the Doris Duke Charitable Foundation Fund to Retain Clinical Scientist Award (to RH). Funding for the CRIC Study was obtained under a cooperative agreement from NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland , UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131. The NIH (and other sponsors) did not have a role in study design, data collection, analysis, or interpretation, or manuscript preparation.
Funding Information:
In addition to author Chen, the CRIC Study Investigators are Lawrence J. Appel, MD, MPH, Harold I. Feldman MD, MSCE, Alan S. Go, MD, Mahboob Rahman, MD, Panduranga S. Rao, MD, Vallabh O. Shah, PhD, MS, Raymond R. Townsend, MD, and Mark L. Unruh, MD, MS. Rasheeda K. Hall, MD, MBA, MHS, Jacob B. Blumenthal, MD, Rebecca M. Doerfler, MPH, Jing Chen, MD, MMSc, MSc, Clarissa J. Diamantidis, MD, MHS, Bernard G. Jaar, MD, John W. Kusek, PhD, Krishna Kallem, MD, MPH, Mary B. Leonard, MD, MSCE, Sankar D. Navaneethan, MD, MS, MPH, Daohang Sha, PhD, James H. Sondheimer, MD, Lee-Ann Wagner, MD, Wei Yang, PhD, Min Zhan, PhD, and Jeffrey C. Fink, MD. Research idea and design: all authors; data acquisition: RMD, JC, CJD, BGJ, JWK, KK, MBL, SDN, JHS, L-AW; data analysis/interpretation: all authors; statistical analysis: DS, WY; supervision or mentorship: JCF. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health (NIH) under Award Number K76AG059930 (to RH) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under Award Number R01DK090008 (to JCF). This study was also supported by the ASN Foundation for Kidney Research (to RH) and the Doris Duke Charitable Foundation Fund to Retain Clinical Scientist Award (to RH). Funding for the CRIC Study was obtained under a cooperative agreement from NIDDK (U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported in part by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/NCATS UL1TR000003, Johns Hopkins University UL1 TR-000424, University of Maryland GCRC M01 RR-16500, Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, Michigan Institute for Clinical and Health Research (MICHR) UL1TR000433, University of Illinois at Chicago CTSA UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology P30GM103337, and Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131. The NIH (and other sponsors) did not have a role in study design, data collection, analysis, or interpretation, or manuscript preparation. The authors declare that they have no relevant financial interests. The authors would like to thank Donna Crabtree at Duke University School of Medicine for her assistance with building supplemental table. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Received October 26, 2020. Evaluated by 3 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Biff F. Palmer, MD). Accepted in revised form March 3, 2021. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.
Publisher Copyright:
© 2021
PY - 2021/12
Y1 - 2021/12
N2 - Rationale & Objective: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls. Study Design: Retrospective observational study. Setting & Participants: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011. Exposure: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria. Outcome: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure. Analytical Approach: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome. Results: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or ≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n = 1,109), prescriptions for ≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes. Limitations: Measurement bias; confounding by indication. Conclusions: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription.
AB - Rationale & Objective: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls. Study Design: Retrospective observational study. Setting & Participants: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011. Exposure: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria. Outcome: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure. Analytical Approach: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome. Results: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or ≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n = 1,109), prescriptions for ≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes. Limitations: Measurement bias; confounding by indication. Conclusions: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription.
KW - Adverse drug event
KW - CKD progression
KW - adverse outcomes
KW - chronic kidney disease (CKD)
KW - drug safety
KW - falls
KW - hospitalizations
KW - kidney replacement therapy (KRT)
KW - mortality
KW - potentially inappropriate medications (PIMs)
KW - prescribing practices
KW - proton pump inhibitors (PPIs)
KW - α-blockers
UR - http://www.scopus.com/inward/record.url?scp=85111271862&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111271862&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2021.03.019
DO - 10.1053/j.ajkd.2021.03.019
M3 - Article
C2 - 34029681
AN - SCOPUS:85111271862
SN - 0272-6386
VL - 78
SP - 837-845.e1
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -