Association of Polypharmacy with Kidney Disease Progression in Adults with CKD

Kimura, Hiroshi; Tanaka, Kenichi; Saito, Hiroko; Iwasaki, Tsuyoshi; Oda, Akira; Watanabe, Shuhei; Kanno, Makoto; Shimabukuro, Michio; Asahi, Koichi; Watanabe, Tsuyoshi; Kazama, Junichiro James

doi:10.2215/cjn.03940321

Cited by 41 publications

(24 citation statements)

References 41 publications

(45 reference statements)

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“…Our results showed that elderly people with excessive polypharmacy (more than ten medications) are six times more likely to have renal impairment compared to elderly with less than ve medications. This is consistent with the literature, which shows that polypharmacy exposure is signi cantly associated with an increased risk of kidney dysfunction (7,28,29). Knowing that pharmacokinetic changes happen with aging, where renal elimination decreases, increases the risk of pharmaceutical ingredient and metabolite accumulation, which in this case increases the risk of renal impairment (9).…”

Section: Discussionsupporting

confidence: 86%

Polypharmacy associated with renal impairment in elderly people attending primary health care centers

Naghnaghia

Nazzal

Abualia

et al. 2022

Preprint

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Purpose: This study aimed to estimate the prevalence of renal impairment among primary health care (PHC) elderly, its association with polypharmacy, and the most frequent potentially inappropriate prescription (PIP) in renal impairment patients. Methods: A cross-sectional study was conducted among PHC clinic attendees aged 65 and older. We used medical records and an interviewer-administered questionnaire for data collection. Participants with eGFR less than 60mls/min/1.73m2 were categorized as renal impaired; we then calculated the prevalence of renal impairment and used multivariable analysis to identify its predictors. Beer's criteria and literature reviews were used to evaluate renal impairment patients' medication and to determine the frequency of PIPs. Results: The study included 421 participants (224 female, 197 male), and 66.3% were between the ages of 65 and 75. The prevalence of renal impairment was 30.2% (95%CI: 25.8-34.6%). Polypharmacy [aOR= 5.9, 95%CI: 2.4-14.6], stroke [aOR= 2.5, 95%CI: 1.2-5.4], Females [aOR= 2.6, 95%CI: 1.5-4.7], and elderly over the age of 80 [aOR= 4.4, 95%CI: 2.2-8.8] were the main predictors of renal impairment. RAAS (54.3%), metformin (39.3%) and sulfonylurea (20.4%) were the most frequent reported PIP in renal impairment patients. Conclusion: Renal impairment affects nearly one-third of elderly Palestinians who attend PHC clinics and has been strongly linked to polypharmacy in this population. Stroke, age, and gender are other identified risk factors in our study. It is recommended to raise healthcare providers' awareness to control elderly patients’ chronic conditions by cautiously prescribing only necessary medication, choosing non-nephrotoxic alternatives, and monitoring their renal function frequently.

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Section: Discussionsupporting

confidence: 86%

Polypharmacy associated with renal impairment in elderly people attending primary health care centers

Naghnaghia

Nazzal

Abualia

et al. 2022

Preprint

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“…In CKD, this adaptive response is lost, and a decrease in transporter expression is observed [33], possibly caused by aberrant gut-to-kidney signaling through increased blood concentrations of uremic toxins [34]. This assumption is further supported by recent observations in which protein-bound uremic toxins may compete with co-administered drugs commonly used in CKD management, which potentially compromise the residual tubular function [25,35,36]. The progressive loss of tubular function and accompanied increase in retention of uremic toxins fuel systemic metabolic disorders and comorbidities associated with the pathophysiology of CKD.…”

Section: Remote Sensing and Signaling: Linking The Kidney To The Gutmentioning

confidence: 88%

The Dual Roles of Protein-Bound Solutes as Toxins and Signaling Molecules in Uremia

Masereeuw

2022

Toxins

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In patients with severe kidney disease, renal clearance is compromised, resulting in the accumulation of a plethora of endogenous waste molecules that cannot be removed by current dialysis techniques, the most often applied treatment. These uremic retention solutes, also named uremic toxins, are a heterogeneous group of organic compounds of which many are too large to be filtered and/or are protein-bound. Their renal excretion depends largely on renal tubular secretion, by which the binding is shifted towards the free fraction that can be eliminated. To facilitate this process, kidney proximal tubule cells are equipped with a range of transport proteins that cooperate in cellular uptake and urinary excretion. In recent years, innovations in dialysis techniques to advance uremic toxin removal, as well as treatments with drugs and/or dietary supplements that limit uremic toxin production, have provided some clinical improvements or are still in progress. This review gives an overview of these developments. Furthermore, the role protein-bound uremic toxins play in inter-organ communication, in particular between the gut (the side where toxins are produced) and the kidney (the side of their removal), is discussed.

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“…A previous cohort comprised of U.S. adults aged ≥45 years with a 5-year follow-up showed that only major polypharmacy (≥ 8 medications) was associated with increased mortality (HR = 1.24 [1.06, 1.45]), but not for minor polypharmacy (6-7 medications) (HR = 1.15 [0.98, 1.36]) in those with CKD, and there was no evidence that this association was modified by CKD status (22). Another Japanese cohort consisting of 1,117 participants reported that both polypharmacy (5-9 medications) and hyperpolypharmacy (≥10 medications) were associated with kidney failure (HR = 2.28 [1.00, 5.21] and HR = 2.83 [1.21, 6.66], respectively), but only hyperpolypharmacy was related to all-cause mortality (HR = 2.80 [1.41-5.54]) (21). However, our sensitivity analysis suggested even minor polypharmacy significantly increased mortality in the elderly CKD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, evidence on polypharmacy and health outcomes in older adults with CKD is scarce. Several cohort studies indicated polypharmacy was associated with an increased risk of kidney failure, fragility fracture, CVD events, and all-cause mortality in patients with CKD (20)(21)(22), even regardless of CKD status (20,22,23).…”

Section: Introductionmentioning

confidence: 99%

Polypharmacy, chronic kidney disease, and mortality among older adults: A prospective study of National Health and nutrition examination survey, 1999–2018

Wang

Yang

Jiang

et al. 2023

Front. Public Health

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IntroductionPolypharmacy might contribute to a range of adverse outcomes, which could get worse in the elderly with chronic kidney disease (CKD). Evidence on polypharmacy, CKD, and mortality is scarce. We aimed to investigate the prospective association between polypharmacy, CKD and all-cause and cause-specific mortality in adults aged ≥65 years.MethodsA total of 13,513 adults from the National Health and Nutrition Examination Surveys were included, following up from 1999 to 2018 until December 31, 2019. The simultaneous use of ≥5 medications by one individual was defined as polypharmacy. Survey-weighted Cox proportional hazard models were used to estimate the hazard ratio (HRs) for mortality from all-cause, cardiovascular diseases (CVD), and cancer after adjusting for potential confounding factors.ResultsAmong the elderly with CKD, we identified 3,825 total deaths (1,325 CVD and 714 cancer) during a median follow-up of 7.7 years. Participants with polypharmacy had a 27% (HR = 1.27 [1.15, 1.39]) and 39% (HR = 1.39 [1.19, 1.62]) higher risk of all-cause and CVD mortality, respectively, but not for cancer mortality. Compared with the elderly with no polypharmacy and no CKD, the corresponding HRs (95%CIs) for all-cause mortality were 1.04 (0.96, 1.14) for those with no polypharmacy but CKD, 1.24 (1.11, 1.39) for with polypharmacy but no CKD, and 1.34 (1.21, 1.49) for those with both polypharmacy and CKD. A similar pattern was detected for CVD mortality.DiscussionPolypharmacy was associated with elevated risks of all-cause and CVD mortality among the elderly CKD patients. More evidence-based approaches should be promoted for the appropriate deprescribing in the older adults with CKD.

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Association of Polypharmacy with Kidney Disease Progression in Adults with CKD

Cited by 41 publications

References 41 publications

Polypharmacy associated with renal impairment in elderly people attending primary health care centers

Polypharmacy associated with renal impairment in elderly people attending primary health care centers

The Dual Roles of Protein-Bound Solutes as Toxins and Signaling Molecules in Uremia

Polypharmacy, chronic kidney disease, and mortality among older adults: A prospective study of National Health and nutrition examination survey, 1999–2018

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