Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial

Background SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (M...

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Autores: Provenzano, Michele, Puchades, Maria, Garofalo, Carlo, Jongs, Niels, D'Marco, Luis, Andreucci, Michele, De Nicola, Luca, Gorriz, Jose, Heerspink, Hiddo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p16568
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/16568
Access Level:acceso abierto
Palavra-chave:albuminuria
aldosterone
chronic kidney disease
randomized controlled trials
sodium glucose co transporter
mineralocorticoid receptor antagonist
dapagliflozin
eplerenone
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spelling Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical TrialProvenzano, MichelePuchades, MariaGarofalo, CarloJongs, NielsD'Marco, LuisAndreucci, MicheleDe Nicola, LucaGorriz, JoseHeerspink, Hiddoalbuminuriaaldosteronechronic kidney diseaserandomized controlled trialssodium glucose co transportermineralocorticoid receptor antagonistdapagliflozineplerenoneBackground SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplere-none alone and in combination in patients with CKD. Methods We conducted a randomized open-label crossover trial in patients with urinary albumin excretion >= 100 mg/24 hours, eGFR 30-90 ml/min per 1.73 m(2), who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-weektreatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in randomorder, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results Of 57 patients screened, 46 were randomly assigned (mean eGFR 58.1 ml/min per 1.73 m(2),median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was-19.6% (95% CI,-34.3 to-1.5),-33.7% (95% CI,-46.1 to-18.5), and-53% (95% CI,-61.7 to-42.4;P < 0.001 versus dapagli-flozin; P > 0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did notcorrelate with UACR change during dapagliflozin-eplerenone (r5-0.13;P50.47;r5-0.08;P50.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n58; 17.4%) compared with dapagliflozin (n50; 0%) or dapagliflozin-eplerenone (n52; 4.3%;P(between-groups)50.003). Conclusions Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenoneresulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirmlong-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. Clinical Trial registry name and registration number: European Union Clinical Trials Register, EU 2017-004641-25.AMER SOC NEPHROLOGY2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/16568JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGYISSN: 10466673ISSNe: 15333450reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p165682026-06-07T16:35:31Z
dc.title.none.fl_str_mv Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
title Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
spellingShingle Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
Provenzano, Michele
albuminuria
aldosterone
chronic kidney disease
randomized controlled trials
sodium glucose co transporter
mineralocorticoid receptor antagonist
dapagliflozin
eplerenone
title_short Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
title_full Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
title_fullStr Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
title_full_unstemmed Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
title_sort Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
dc.creator.none.fl_str_mv Provenzano, Michele
Puchades, Maria
Garofalo, Carlo
Jongs, Niels
D'Marco, Luis
Andreucci, Michele
De Nicola, Luca
Gorriz, Jose
Heerspink, Hiddo
author Provenzano, Michele
author_facet Provenzano, Michele
Puchades, Maria
Garofalo, Carlo
Jongs, Niels
D'Marco, Luis
Andreucci, Michele
De Nicola, Luca
Gorriz, Jose
Heerspink, Hiddo
author_role author
author2 Puchades, Maria
Garofalo, Carlo
Jongs, Niels
D'Marco, Luis
Andreucci, Michele
De Nicola, Luca
Gorriz, Jose
Heerspink, Hiddo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv albuminuria
aldosterone
chronic kidney disease
randomized controlled trials
sodium glucose co transporter
mineralocorticoid receptor antagonist
dapagliflozin
eplerenone
topic albuminuria
aldosterone
chronic kidney disease
randomized controlled trials
sodium glucose co transporter
mineralocorticoid receptor antagonist
dapagliflozin
eplerenone
description Background SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplere-none alone and in combination in patients with CKD. Methods We conducted a randomized open-label crossover trial in patients with urinary albumin excretion >= 100 mg/24 hours, eGFR 30-90 ml/min per 1.73 m(2), who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-weektreatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in randomorder, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results Of 57 patients screened, 46 were randomly assigned (mean eGFR 58.1 ml/min per 1.73 m(2),median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was-19.6% (95% CI,-34.3 to-1.5),-33.7% (95% CI,-46.1 to-18.5), and-53% (95% CI,-61.7 to-42.4;P < 0.001 versus dapagli-flozin; P > 0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did notcorrelate with UACR change during dapagliflozin-eplerenone (r5-0.13;P50.47;r5-0.08;P50.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n58; 17.4%) compared with dapagliflozin (n50; 0%) or dapagliflozin-eplerenone (n52; 4.3%;P(between-groups)50.003). Conclusions Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenoneresulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirmlong-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. Clinical Trial registry name and registration number: European Union Clinical Trials Register, EU 2017-004641-25.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/16568
url https://incliva.portalinvestigacion.com/publicaciones/16568
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv AMER SOC NEPHROLOGY
publisher.none.fl_str_mv AMER SOC NEPHROLOGY
dc.source.none.fl_str_mv JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN: 10466673
ISSNe: 15333450
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
repository.name.fl_str_mv
repository.mail.fl_str_mv
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