Evidence map›Paper›PMID 40905476›Full record

ReviewEuropean heart journal2025

Decline in glomerular filtration rate as an endpoint in heart failure clinical trials: challenges and solutions.

Lesley A Inker, Brendon L Neuen, Wendy McCallum, Muthiah Vaduganathan, Tom Greene, Hiddo J L Heerspink

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
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

6 authors.

Lesley A InkerDivision of Nephrology, Tufts Medical Center, 800 Washington Street, Box #391, Boston 02111, MA, USA.ORCID 0000-0003-2820-9482
Brendon L NeuenThe George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0001-9276-8380
Wendy McCallumDivision of Nephrology, Tufts Medical Center, 800 Washington Street, Box #391, Boston 02111, MA, USA.ORCID 0000-0003-1860-6302
Muthiah VaduganathanCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0885-1953
Tom GreenePopulation Health Sciences, University of Utah School of Medicine, Salt Lake City, UT, USA.ORCID 0000-0002-3706-7570
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.ORCID 0000-0002-3126-3730

Funding

Improving Kidney Function Assessment in Health and DiseaseR01DK116790 · NIDDK · TUFTS MEDICAL CENTER · PI INKER, LESLEY ANN · 2021 to 2024
$2.9M
Relation between acute changes in kidney function with clinical outcomes among patients with heart failureK23DK128657 · NIDDK · TUFTS MEDICAL CENTER · PI Wendy MCCALLUM · 2023 to 2026
$765k
NIDDK NIH HHS K23 DK128657NIDDK NIH HHS R01 DK116790Tufts Medical Centerfrom the National Institute of Diabetes and Digestive and Kidney Diseases
6 · The paper itself

Abstract

Chronic kidney disease (CKD) and cardiovascular disease are tightly interconnected, with common mechanisms that underlie the development and progression of both diseases, recently articulated into the framework of the cardiovascular-kidney-metabolic syndrome. CKD and heart failure commonly coexist in the same individual, with increasing evidence for common therapies in both disease states. It is valuable for patients, clinicians, and regulatory agencies to understand how to best assess CKD progression in patients with heart failure for evaluation of individual patients and as part of an endpoint for outcome trials. Given the relatively short duration of most heart failure outcome trials, early measures of CKD progression prior to the occurrence of clinical events of kidney replacement therapy would be desirable. Such surrogate measures include slowing of the decline in glomerular filtration rate (GFR) decline either computed as annualized mean change in GFR (GFR slope) or time to substantial declines in GFR by specified threshold percentages (40% or 50% GFR decline). Regulatory agencies accept these endpoints for full drug approval which has enabled progress in design and conduct of trials for CKD progression. Application of these endpoints in heart failure outcome trials has the potential for similar progress. However, an immediate reduction in GFR is common following initiation of several of the guideline directed therapy for heart failure. Understanding how to best interpret an immediate GFR reduction vs long term kidney benefit is critical to optimal assessment of endpoint in an outcome trial and in the use of these medications for management of patients with heart failure. Here, the intersection of heart failure and CKD is described, how GFR and its change over time are assessed in both individual patients and in interventional trials, the evidence supporting use of GFR changes as endpoints in CKD progression trials, and the challenges and possible solutions for the use of GFR as endpoint in heart failure outcome trials and for care of individual patients, guided by case studies to inform the discussion.

Indexed as

Glomerular Filtration RateHeart FailureRenal Insufficiency, ChronicClinical Trials as TopicDisease ProgressionEndpoint DeterminationHumansChronic kidney diseaseGFR slopeGlomerular filtration rateHeart failureRandomized control trials

Identifiers

PMID40905476
PMCPMC13047564

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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.