Please use this identifier to cite or link to this item: http://hdl.handle.net/10637/16173

Glomerular and tubular effects of Dapagliflozin, Eplerenone and their combination in patients with Chronic Kidney Disease: a post-hoc analysis of the ROTATE-3 study


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Title: Glomerular and tubular effects of Dapagliflozin, Eplerenone and their combination in patients with Chronic Kidney Disease: a post-hoc analysis of the ROTATE-3 study
Authors : Lieverse, Tom T. G. F.
Puchades, María Jesús
Mulder, Udo D. J.
Provenzano, Michele
Krenning, Guido
Jongs, Niels
Wink, Simon E.
Slart, Riemer H. J. A.
Andreucci, Michele
D'Marco Gascón, Luis Gerardo
De Nicola, Luca
Górriz, José Luis
Heerspink, Hiddo J. L.
Keywords: DapagliflozinaDapagliflozinEplerenonaEplerenoneAlbuminuriaDiseasesEnfermedadUrinary systemSistema urinarioMedical treatmentTratamiento médicoDrugsMedicamento
Publisher: John Wiley & Sons
Citation: Lieverse, T.T.G.F., Puchades, M.J., Mulder, U.D.J., Provenzano, M., Krenning, G., Jongs, N., Wink, S.E., Slart, R.H.J.A., Andreucci, M., D'Marco, L., De Nicola, L., Gorriz, J.L. & Heerspink, H.J.L. (2024). Glomerular and tubular effects of Dapagliflozin, Eplerenone and their combination in patients with Chronic Kidney Disease: a post-hoc analysis of the ROTATE-3 study. Diabetes, Obesity & Metabolism, vol. 26, i. 2 (feb.), pp. 576–582. DOI: https://doi.org/10.1111/dom.15346
Abstract: Aim: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function. Methods: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models. Results: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)]. Conclusions: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects.
URI: http://hdl.handle.net/10637/16173
Rights : http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
Open Access
ISSN: 1462-8902
1463-1326 (Electrónico)
Issue Date: Feb-2024
Center : Universidad Cardenal Herrera-CEU
Appears in Collections:Dpto. Medicina y Cirugía





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