Evidence map›Paper›PMID 40179340›Full record

Trial reportClinical journal of the American Society of Nephrology : CJASN2024

Frailty, Multimorbidity, and Polypharmacy: Exploratory Analyses of the Effects of Empagliflozin from the EMPA-KIDNEY Trial.

Kaitlin J Mayne, Rebecca J Sardell, Natalie Staplin, Parminder K Judge, Doreen Zhu, Emily Sammons, David Z I Cherney, Alfred K Cheung, Aldo P Maggioni, Masaomi Nangaku and 12 more

Abstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Clinical journal of the American Society of Nephrology : CJASN, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Review
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  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. The use of SGLT2 inhibitors in older people: What is important?Aging clinical and experimental research · 2025
    Review
  14. Review
  15. Maintaining kidney health in aging societies: a JSN and ERA call to action.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  16. Article
  17. Review
  18. The potential for improving cardio-renal outcomes in chronic kidney disease with the aldosterone synthase inhibitor vicadrostat (BI 690517): a rationale for the EASi-KIDNEY trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Kaitlin J MayneRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-5695-0270
Rebecca J SardellRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Natalie StaplinRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-4482-4418
Parminder K JudgeRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-0083-3649
Doreen ZhuRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Emily SammonsRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-8647-0366
David Z I CherneyUniversity of Toronto, Toronto, Ontario, Canada.
Alfred K CheungUniversity of Utah, Salt Lake City, Utah.
Aldo P MaggioniAssociazione Nazionale Medici Cardiologi Ospedalieri Research Centre, Florence, Italy.ORCID 0000-0003-2764-6779
Masaomi NangakuUniversity of Tokyo School of Medicine, Tokyo, Japan.ORCID 0000-0001-7401-2934
Xavier RosselloHospital Universitari Son Espases, Health Research Institute of the Balearic Islands, University of the Balearic Islands, Palma de Mallorca, Spain.ORCID 0000-0001-6783-8463
Katherine R TuttleUniversity of Washington, Seattle, Washington.ORCID 0000-0002-2235-0103
Katsuhito IharaMedicine Division, Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan.ORCID 0000-0001-9554-3646
Tomoko IwataBoehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
Christoph WannerRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-9507-5301
Jonathan EmbersonRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-7792-9422
David PreissRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-3139-1836
Martin J LandrayRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-6646-827
Colin BaigentRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Richard HaynesRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-1179-0023
William G HerringtonRenal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
EMPA-KIDNEY Collaborative Group

Funding

Boehringer IngelheimEli Lilly and CompanyMedical Research Council MC_UU_00017/3Medical Research Council MC_UU_00017/4Medical Research Council MR/R007764/1
6 · The paper itself

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors are recommended treatment for adults with CKD, but uncertainty exists regarding their use in patients with frailty and/or multimorbidity, among whom polypharmacy is common. We derived a multivariable logistic regression model to predict hospitalization (reflecting frailty) and assessed empagliflozin's risk–benefit profile in a post hoc analysis of the double-blind, placebo-controlled EMPA-KIDNEY trial. Methods: The EMPA-KIDNEY trial randomized 6609 patients with CKD (eGFR ≥20 to <45 ml/min per 1.73 m2, or ≥45 to <90 ml/min per 1.73 m2 with urinary albumin-to-creatinine ratio ≥200 mg/g) to receive either empagliflozin 10 mg daily or matching placebo and followed them for 2 years (median). Additional characteristics analyzed in subgroups were multimorbidity, polypharmacy, and health-related quality of life at baseline. Cox regression analyses were performed with subgroups defined by approximate thirds of each variable. Results: The strongest predictors of hospitalization were N-terminal prohormone of brain natriuretic peptide, poor mobility, and diabetes and then eGFR and other comorbidities. Empagliflozin was generally well tolerated independent of predicted risk of hospitalization. In relative terms, allocation to empagliflozin reduced the risk of the primary outcome of kidney disease progression or cardiovascular death by 28% (hazard ratio, 0.72; 95% confidence interval, 0.64 to 0.82) and all-cause hospitalization by 14% (hazard ratio, 0.86; 95% confidence interval, 0.78 to 0.95), with broadly consistent effects across subgroups of predicted risk of hospitalization, multimorbidity, polypharmacy, or health-related quality of life. In absolute terms, the estimated benefits of empagliflozin were greater in those at highest predicted risk of hospitalization (reflecting frailty) and outweighed potential serious harms. Conclusions: These findings support the use of sodium-glucose cotransporter-2 inhibitors in CKD, irrespective of frailty, multimorbidity, or polypharmacy.

Indexed as

Benzhydryl CompoundsFrailtyGlucosidesPolypharmacyRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAgedDouble-Blind MethodFemaleGlomerular Filtration RateHospitalizationHumansMaleMiddle AgedMultimorbidityQuality of LifeBenzhydryl CompoundsempagliflozinGlucosidesSodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID40179340
PMCPMC11390031

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.