Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Geriatrics
Published in: BMC Geriatrics 1/2024

Open Access 01-12-2024 | Chronic Kidney Disease | Research

Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults

Authors: Nina Mielke, Muhammad Helmi Barghouth, Anne-Katrin Fietz, Cédric Villain, Tim Bothe, Natalie Ebert, Elke Schaeffner

Published in: BMC Geriatrics | Issue 1/2024

Login to get access

Abstract

Background

Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults.

Methods

In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD.

Results

In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20–3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01–3.12).

Conclusions

This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.
Appendix
Available only for authorised users
Literature
1.
2.
Mehta RS, Kochar BD, Kennelty K, Ernst ME, Chan AT. Emerging approaches to polypharmacy among older adults. Nat Aging. 2021;1(4):347–56.PubMedCrossRef
3.
4.
O’Caoimh R, Sezgin D, O’Donovan MR, Molloy DW, Clegg A, Rockwood K, Liew A. Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies. Age Ageing. 2021;50(1):96–104.PubMedCrossRef
5.
Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. Journals Gerontol Ser A: Biol Sci Med Sci. 2001;56(3):M146–57.CrossRef
6.
Bandeen-Roche K, Xue Q-L, Ferrucci L, Walston J, Guralnik JM, Chaves P, et al. Phenotype of frailty: characterization in the women’s health and aging studies. Journals Gerontol Ser A: Biol Sci Med Sci. 2006;61(3):262–6.CrossRef
7.
Gutiérrez-Valencia M, Izquierdo M, editors. others. The relationship between frailty and polypharmacy in older people: A systematic review. British journal of. 2018.
8.
Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Cumming RG, Handelsman DJ, et al. High-risk prescribing and incidence of frailty among older community-dwelling men. Clin Pharmacol Ther. 2012;91(3):521–8.PubMedCrossRef
9.
Saum KU, Schottker B, Meid AD, Holleczek B, Haefeli WE, Hauer K, Brenner H. Is polypharmacy associated with frailty in older people? Results from the ESTHER Cohort Study. J Am Geriatr Soc. 2017;65(2):e27–32.PubMedCrossRef
10.
Jamsen KM, Bell JS, Hilmer SN, Kirkpatrick CM, Ilomaki J, Le Couteur D, et al. Effects of changes in number of medications and drug burden index exposure on transitions between frailty states and death: the concord health and ageing in men project cohort study. J Am Geriatr Soc. 2016;64(1):89–95.PubMedCrossRef
11.
Trevisan C, Veronese N, Maggi S, Baggio G, Toffanello ED, Zambon S, et al. Factors influencing transitions between frailty states in elderly adults: the Progetto Veneto Anziani longitudinal study. J Am Geriatr Soc. 2017;65(1):179–84.PubMedCrossRef
12.
Wang R, Chen L, Fan L, Gao D, Liang Z, He J, et al. Incidence and effects of polypharmacy on clinical outcome among patients aged 80+: a five-year follow-up study. PLoS ONE. 2015;10(11):e0142123.PubMedPubMedCentralCrossRef
13.
Shmuel S, Lund JL, Alvarez C, Hsu CD, Palta P, Kucharska-Newton A, et al. Polypharmacy and incident frailty in a longitudinal community-based cohort study. J Am Geriatr Soc. 2019;67(12):2482–9.PubMedCrossRef
14.
Palmer K, Villani ER, Vetrano DL, Cherubini A, Cruz-Jentoft AJ, Curtin D, et al. Association of polypharmacy and hyperpolypharmacy with frailty states: a systematic review and meta-analysis. Eur Geriatr Med. 2019;10(1):9–36.PubMedCrossRef
15.
Kimura H, Tanaka K, Saito H, Iwasaki T, Oda A, Watanabe S, et al. Association of polypharmacy with kidney disease progression in adults with CKD. Clin J Am Soc Nephrol. 2021;16(12):1797–804.PubMedPubMedCentralCrossRef
16.
Mielke N, Schneider A, Barghouth MH, Ebert N, van der Giet M, Huscher D et al. Association of kidney function and albuminuria with frailty worsening and death in very old adults. Age Ageing. 2023;52(5).
17.
Walker SR, Gill K, Macdonald K, Komenda P, Rigatto C, Sood MM, et al. Association of frailty and physical function in patients with non-dialysis CKD: a systematic review. BMC Nephrol. 2013;14:228.PubMedPubMedCentralCrossRef
18.
Bruck K, Stel VS, Gambaro G, Hallan S, Volzke H, Arnlov J, et al. CKD prevalence varies across the European general population. J Am Soc Nephrol. 2016;27(7):2135–47.PubMedCrossRef
19.
Tonelli M, Wiebe N, Guthrie B, James MT, Quan H, Fortin M, et al. Comorbidity as a driver of adverse outcomes in people with chronic kidney disease. Kidney Int. 2015;88(4):859–66.PubMedCrossRef
20.
Sundstrom J, Bodegard J, Bollmann A, Vervloet MG, Mark PB, Karasik A, et al. Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2.4 million patients from 11 countries: the CaReMe CKD study. Lancet Reg Health Eur. 2022;20:100438.PubMedPubMedCentralCrossRef
21.
Laville SM, Gras-Champel V, Moragny J, Metzger M, Jacquelinet C, Combe C, et al. Adverse drug reactions in patients with CKD. Clin J Am Soc Nephrol. 2020;15(8):1090–102.PubMedPubMedCentralCrossRef
22.
Schaeffner ES, van der Giet M, Gaedeke J, Tolle M, Ebert N, Kuhlmann MK, Martus P. The Berlin initiative study: the methodology of exploring kidney function in the elderly by combining a longitudinal and cross-sectional approach. Eur J Epidemiol. 2010;25(3):203–10.PubMedCrossRef
23.
Ebert N, Jakob O, Gaedeke J, van der Giet M, Kuhlmann MK, Martus P, et al. Prevalence of reduced kidney function and albuminuria in older adults: the Berlin initiative study. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association -. Eur Ren Association. 2017;32(6):997–1005.
24.
Mielke N, Huscher D, Douros A, Ebert N, Gaedeke J, van der Giet M, et al. Self-reported medication in community-dwelling older adults in Germany: results from the Berlin initiative study. BMC Geriatr. 2020;20(1):22.PubMedPubMedCentralCrossRef
25.
Mielke N, Schneider A, Huscher D, Ebert N, Schaeffner E. Gender differences in frailty transition and its prediction in community-dwelling old adults. Sci Rep. 2022;12(1):7341.PubMedPubMedCentralCrossRef
26.
Savva GM, Donoghue OA, Horgan F, O’Regan C, Cronin H, Kenny RA. Using timed up-and-go to identify frail members of the older population. The journals of gerontology Series A, Biological sciences and medical sciences. 2013;68(4):441–6.
27.
Brauns H, Scherer S, Steinmann S. The CASMIN educational classification in international comparative research. In: Hoffmeyer-Zlotnik JHPW, C., editor. editor. Advances in cross-national comparison. New York: Kluwer; 2003. pp. 221–44.CrossRef
28.
Schaeffner ES, Ebert N, Delanaye P, Frei U, Gaedeke J, Jakob O, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471–81.PubMedCrossRef
29.
Kidney Disease. Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Supplements. 2013;3(1):1–150.
30.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.PubMedCrossRef
31.
Greenland S, Pearl J, Robins JM. Causal diagrams for epidemiologic research. Epidemiology. 1999;10(1):37–48.PubMedCrossRef
32.
Wastesson JW, Morin L, Tan ECK, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opin Drug Saf. 2018;17(12):1185–96.PubMedCrossRef
33.
34.
Greenland S, Lash TL, Rothman KJ. Concepts of Interaction. In: Rothman KJ, Greenland S, Lash TL, editors. Modern epidemiology. 3 ed. Philadelphia, USA: Lippincott Williams & Wilkins; 2008.
35.
Vandenbroucke JP, von Elm E, Altman DG, Gotzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. Epidemiology. 2007;18(6):805–35.PubMedCrossRef
36.
Alli BY. InteractionR: an R package for full reporting of effect modification and interaction. Softw Impacts. 2021;10.
37.
Midao L, Giardini A, Menditto E, Kardas P, Costa E. Polypharmacy prevalence among older adults based on the survey of health, ageing and retirement in Europe. Arch Gerontol Geriatr. 2018;78:213–20.PubMedCrossRef
38.
Strampelli A, Cerreta F, Vucic K. Medication use among older people in Europe: implications for regulatory assessment and co-prescription of new medicines. Br J Clin Pharmacol. 2020;86(10):1912–20.PubMedPubMedCentralCrossRef
39.
Ofori-Asenso R, Chin KL, Mazidi M, Zomer E, Ilomaki J, Zullo AR, et al. Global incidence of frailty and prefrailty among community-dwelling older adults: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(8):e198398.PubMedPubMedCentralCrossRef
40.
Randles MA, O’Mahony D, Gallagher PF. Frailty and potentially inappropriate prescribing in older people with polypharmacy: a bi-directional relationship? Drugs Aging. 2022;39(8):597–606.PubMedPubMedCentralCrossRef
41.
Little MO. Updates in nutrition and polypharmacy. Curr Opin Clin Nutr Metab Care. 2018;21(1):4–9.PubMedCrossRef
42.
Thanoo N, Gilbert AL, Trainor S, Semanik PA, Song J, Lee J, et al. The relationship between polypharmacy and physical activity in those with or at risk of knee osteoarthritis. J Am Geriatr Soc. 2020;68(9):2015–20.PubMedPubMedCentralCrossRef
43.
44.
Secora A, Alexander GC, Ballew SH, Coresh J, Grams ME. Kidney function, polypharmacy, and potentially inappropriate medication use in a community-based cohort of older adults. Drugs Aging. 2018;35(8):735–50.PubMedPubMedCentralCrossRef
45.
Knol MJ, VanderWeele TJ, Groenwold RH, Klungel OH, Rovers MM, Grobbee DE. Estimating measures of interaction on an additive scale for preventive exposures. Eur J Epidemiol. 2011;26(6):433–8.PubMedPubMedCentralCrossRef
46.
Lu Y, Nyunt MSZ, Gao Q, Gwee X, Chua DQ, Yap KB et al. Malnutrition risk and kidney function and decline in community-dwelling older adults. J Ren Nutr. 2022.
47.
Sommer J, Seeling A, Rupprecht H. Adverse drug events in patients with chronic kidney disease associated with multiple drug interactions and polypharmacy. Drugs Aging. 2020;37(5):359–72.PubMedCrossRef
48.
Lun P, Law F, Ho E, Tan KT, Ang W, Munro Y, Ding YY. Optimising prescribing practices in older adults with multimorbidity: a scoping review of guidelines. BMJ Open. 2021;11(12):e049072.PubMedPubMedCentralCrossRef
49.
50.
Khezrian M, McNeil CJ, Murray AD, Myint PK. An overview of prevalence, determinants and health outcomes of polypharmacy. Ther Adv Drug Saf. 2020;11:2042098620933741.PubMedPubMedCentralCrossRef
51.
52.
Ouellet GM, Ouellet JA, Tinetti ME. Principle of rational prescribing and deprescribing in older adults with multiple chronic conditions. Ther Adv Drug Saf. 2018;9(11):639–52.PubMedPubMedCentralCrossRef
53.
Gillespie RJ, Harrison L, Mullan J. Deprescribing medications for older adults in the primary care context: a mixed studies review. Health Sci Rep. 2018;1(7):e45.PubMedPubMedCentralCrossRef
Metadata
Title
Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults
Authors
Nina Mielke
Muhammad Helmi Barghouth
Anne-Katrin Fietz
Cédric Villain
Tim Bothe
Natalie Ebert
Elke Schaeffner
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2024
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-024-04887-5

Other articles of this Issue 1/2024

BMC Geriatrics 1/2024 Go to the issue

Research

Influencing factors, gender differences and the decomposition of inequalities in cognitive function in Chinese older adults: a population-based cohort study

Research

Older people’s perception of being frail – a qualitative exploration

Study Protocol

Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol

Research

The Danish Aging and Cognition (DanACo) cohort

Correction

Correction: Psychometric evaluation of the Decision Support System (DSS) for municipal nurses encountering health deterioration among older adults

Research

Dependency and frailty in the older haemodialysis patient
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits