Evidence map›Paper›PMID 41223002›Full record

Trial reportKidney3602026

Dapagliflozin Mitigates Medullary Hypoxia in CKD Patients: Analysis of Blood Oxygenation Level-Dependent Magnetic Resonance Imaging Renal Data from the Randomized Glucose Transport and Renal Protection in CKD Trial.

Elisa Russo, Emilio Venturelli, Julie Di Vincenzo, Lucia Macciò, Pasquale Esposito, Francesca Cappadona, Giulio Ferrazzi, Rocco Grillo, Maria Beatrice Damasio, Giacomo Garibotto and 1 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Kidney360, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT05998837. 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.

NCT05998837 phase2 / phase3completed

Single-center, Randomized, Controlled Study to Evaluate the Effects of a Six-month Treatment With Renal Glucose Transport Inhibitor (SGLT2i) Drugs on Markers of Senescence, Inflammation and Tubulointerstitial Damage in the Kidney of Patients With Chronic Kidney Disease With or Without Type 2 Diabetes

Ran2021Enrolled34Registered outcomes8Posted comparisons0ConditionsChronic Kidney Disease, Diabetes Mellitus, Type 2, HypertensionArmsDapagliflozin 10mg Tab, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. 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

11 authors.

Elisa RussoNephrology, Dialysis and Transplantation Unit, IRCCS Policlinico San Martino, Genoa, Italy.ORCID 0000-0003-1279-3178
Emilio VenturelliDepartment of Internal Medicine, University of Genoa, Genoa, Italy.
Julie Di VincenzoDepartment of Internal Medicine, University of Genoa, Genoa, Italy.
Lucia MacciòNephrology, Dialysis and Transplantation Unit, IRCCS Policlinico San Martino, Genoa, Italy.ORCID 0009-0006-7018-6367
Pasquale EspositoNephrology, Dialysis and Transplantation Unit, IRCCS Policlinico San Martino, Genoa, Italy.ORCID 0000-0002-0834-5586
Francesca CappadonaDepartment of Internal Medicine, University of Genoa, Genoa, Italy.ORCID 0009-0008-8264-5318
Giulio FerrazziPhilips Healthcare, Milan, Italy.ORCID 0000-0001-7449-4718
Rocco GrilloRadiology Department, IRCCS Istituto Giannina Gaslini, Genova, Italy.ORCID 0009-0009-4420-8691
Maria Beatrice DamasioRadiology Department, IRCCS Istituto Giannina Gaslini, Genova, Italy.ORCID 0000-0001-6737-1090
Giacomo GaribottoDepartment of Internal Medicine, University of Genoa, Genoa, Italy.ORCID 0000-0001-6432-2429
Francesca ViazziNephrology, Dialysis and Transplantation Unit, IRCCS Policlinico San Martino, Genoa, Italy.ORCID 0000-0003-4219-7043

Funding

AstraZeneca
6 · The paper itself

Abstract

key pointsDapagliflozin significantly improves renal medullary oxygenation in CKD, constituting a potential mechanism of its nephroprotection. The enhancement of medullary oxygenation is more pronounced in nondiabetic patients, suggesting a distinct pathophysiologic response. Blood oxygenation level-dependent magnetic resonance imaging represents a promising noninvasive biomarker for assessing renal oxygenation.

backgroundRenal hypoxia is believed to play a central role in the pathophysiology of both diabetic and nondiabetic CKD. Dapagliflozin has been shown to slow the progression of kidney disease by counteracting several pathogenic mechanisms. The advent of blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) has enabled the noninvasive assessment of renal oxygenation in humans. However, it remains uncertain whether dapagliflozin affects changes in renal oxygenation. The aim of the study was to assess whether dapagliflozin modifies kidney oxygenation measured by BOLD-MRI.

methodsThe GLUcose Transport and Renal PROtection in chronic kidney disease study is a randomized controlled clinical trial investigating the effect of dapagliflozin on kidney measures. Here, we investigate whether changes in global and segmental renal oxygenation estimated by BOLD-MRI (namely, changes in R2* parameter) can be measured, after randomization to dapagliflozin or placebo. We analyzed data from 720 pairs of regions of interest of 20 patients who underwent BOLD-MRI on a 3T magnetic resonance imaging scanner, comparing baseline measurements against the ones obtained after 3 months from the onset of treatment.

resultsAfter 12 weeks, dapagliflozin treatment significantly reduced the medullary R2* relaxation rate, indicating improved oxygenation ( P = 0.015), while cortical R2* remained unchanged ( P = 0.56). This effect was more pronounced in nondiabetic patients. Dapagliflozin was identified as the sole independent determinant of improved medullary renal oxygenation ( β , -14.4; 95% confidence interval, -23.9 to -4.89; P = 0.003) after accounting for other confounding factors such as age, presence of diabetes or macroalbuminuria, and BP levels. In addition, dapagliflozin appeared to alter the relationship between changes in renal oxygenation and the eGFR slope.

conclusionsThese findings suggest that dapagliflozin may mitigate medullary hypoxia in patients with CKD. BOLD-MRI could serve as a valuable biomarker for assessing renal functional reserve and predicting CKD progression. Further studies are warranted to confirm these effects and explore underlying molecular mechanisms. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: EudraCT, 2020-004835-26 ; ClinicalTrials.gov, NCT05998837 .

Indexed as

Benzhydryl CompoundsGlucosidesHypoxiaKidney MedullaOxygenRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAdultAgedFemaleGlucoseHumansMagnetic Resonance ImagingMaleMiddle AgedBenzhydryl CompoundsdapagliflozinGlucoseGlucosidesOxygenSodium-Glucose Transporter 2 Inhibitorschronic hypoxiaCKDclinical trialkidney tubuleprogression of renal failureSGLT2

Identifiers

PMID41223002
PMCPMC13065203

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Registered trials

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.