Dapagliflozin attenuates progression from prefrailty to frailty in patients with hypertension and chronic kidney disease.
10 affiliations
- 1Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy.
- 2Clinica Montevergine, GVM Care and Research, Mercogliano (Avellino), Italy.
- 3Division of Internal Medicine, Veneziale Hospital, Isernia, Italy.
- 4Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy.
- 5Local Health Unit of the Italian Ministry of Health (ASL), Avellino, Italy.
- 6Department of Medicine, Surgery, and Dentistry, “Scuola Medica Salernitana”, University of Salerno, Baronissi (Salerno), Italy.
- 7Local Health Unit of the Italian Ministry of Health (ASL), Naples, Italy.
- 8Vascular Physiopathology Unit, IRCCS “Neuromed - Mediterranean Neurological Institute”, Pozzilli, Italy.
- 9San Pio Hospital, Benevento, Italy.
- 10Department of Molecular, Cellular, and Biomedical Sciences, City University of New York, School of Medicine, Manhattan, New York, USA
Abstract
BACKGROUNDChronic kidney disease (CKD) and hypertension share common pathophysiological pathways contributing to vascular damage, endothelial dysfunction, and physical decline, particularly in older adults with prefrailty. To evaluate the relationship among renal injury, physical performance, and frailty progression in hypertensive older adults with CKD and assess whether dapagliflozin associates with reduced frailty progression, we designed the study DAPA-FORTRESS (DAPAgliflozin and Frailty prOgression in hypeRTension and chRonic kidnEy diSeaSe).METHODSWe enrolled 135 prefrail hypertensive patients with CKD aged >65 years and followed them for 1 year. After coarsened exact matching, our balanced cohort had 105 patients (52 dapagliflozin). Associations between albuminuria, estimated glomerular filtration rate (eGFR), and physical performance were analyzed using correlation and regression models. Effect of dapagliflozin on frailty progression was evaluated using multivariable logistic regression.RESULTSA significant inverse association between gait speed and albuminuria (r2 = 0.48, P < 0.0001) and significant positive linear association between gait speed and eGFR (r2 = 0.18; P < 0.0001) were observed. Patients with eGFR <60 mL/min/1.73 m2 exhibited significantly worse physical performance than those with higher eGFR (P = 0.0003). In adjusted analyses, receiving dapagliflozin was independently associated with lower odds of progressing to frailty at 1 year (OR = 0.130; CI 0.045-0.381; P < 0.001).CONCLUSIONIn older hypertensive patients with CKD, greater renal injury is associated with worse physical performance, while dapagliflozin use reduces the risk of frailty progression. These findings indicate a potential protective role of sodium-glucose cotransporter 2 inhibition in mitigating functional decline in this high-risk population.FUNDINGNIH: National Heart, Lung, and Blood Institute (R01-HL146691), National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK123259); American Heart Association (AHA- 24IPA1268813, AHA-22-915561, AHA-24-1195524).
Related
- Influence of Perioperative Variables on Surgical Site Infection in Patients With Frailty and Prefrailty Undergoing Coronary Artery Bypass Grafting: Retrospective Multicenter Study
- Short-term clinical efficacy and recorded adverse events of semaglutide combined with dapagliflozin in patients with type 2 diabetes mellitus and chronic kidney disease
- Real-World Renal Effects of Dapagliflozin in Bulgarian Patients with Chronic Kidney Disease of Predominantly Glomerular Origin: A Two-Year Comparative Cohort Study with Historical Controls
- Antialbuminuric Effect of Dapagliflozin Correlates With Urinary Epidermal Growth Factor in Real-World Patients With Diabetic Kidney Disease
- Electroacupuncture attenuates high-salt-induced hypertension by modulating neuronal excitability and proteomic signatures in the paraventricular nucleus of mice
BibTeX
@article{mone2026dapagliflozin,
title = {{Dapagliflozin attenuates progression from prefrailty to frailty in patients with hypertension and chronic kidney disease.}},
author = {Pasquale Mone and Davide Viggiano and Antonella Pansini and Maria Virginia Soldovieri and Giada Sabatelli and Valeria Visco and Gaetano Macina and Eugenio Boccalone and Michele Ciccarelli and Giuseppe Martinelli and Marco Di Mauro and Carmine Vecchione and Maria Morgante and Fahimeh Varzideh and Germano Guerra and Gaetano Santulli},
journal = {The Journal of clinical investigation},
year = {2026},
month = nov,
doi = {10.1172/jci205416},
url = {https://europepmc.org/article/MED/42969229},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dapagliflozin attenuates progression from prefrailty to frailty in patients with hypertension and chronic kidney disease.
AU - Pasquale Mone
AU - Davide Viggiano
AU - Antonella Pansini
AU - Maria Virginia Soldovieri
AU - Giada Sabatelli
AU - Valeria Visco
AU - Gaetano Macina
AU - Eugenio Boccalone
AU - Michele Ciccarelli
AU - Giuseppe Martinelli
AU - Marco Di Mauro
AU - Carmine Vecchione
AU - Maria Morgante
AU - Fahimeh Varzideh
AU - Germano Guerra
AU - Gaetano Santulli
PY - 2026
DA - 2026/11/02
JO - The Journal of clinical investigation
DO - 10.1172/jci205416
UR - https://europepmc.org/article/MED/42969229
AB - BACKGROUNDChronic kidney disease (CKD) and hypertension share common pathophysiological pathways contributing to vascular damage, endothelial dysfunction, and physical decline, particularly in older adults with prefrailty. To evaluate the relationship among renal injury, physical performance, and frailty progression in hypertensive older adults with CKD and assess whether dapagliflozin associates with reduced frailty progression, we designed the study DAPA-FORTRESS (DAPAgliflozin and Frailty prOgression in hypeRTension and chRonic kidnEy diSeaSe).METHODSWe enrolled 135 prefrail hypertensive patients with CKD aged >65 years and followed them for 1 year. After coarsened exact matching, our balanced cohort had 105 patients (52 dapagliflozin). Associations between albuminuria, estimated glomerular filtration rate (eGFR), and physical performance were analyzed using correlation and regression models. Effect of dapagliflozin on frailty progression was evaluated using multivariable logistic regression.RESULTSA significant inverse association between gait speed and albuminuria (r2 = 0.48, P < 0.0001) and significant positive linear association between gait speed and eGFR (r2 = 0.18; P < 0.0001) were observed. Patients with eGFR <60 mL/min/1.73 m2 exhibited significantly worse physical performance than those with higher eGFR (P = 0.0003). In adjusted analyses, receiving dapagliflozin was independently associated with lower odds of progressing to frailty at 1 year (OR = 0.130; CI 0.045-0.381; P < 0.001).CONCLUSIONIn older hypertensive patients with CKD, greater renal injury is associated with worse physical performance, while dapagliflozin use reduces the risk of frailty progression. These findings indicate a potential protective role of sodium-glucose cotransporter 2 inhibition in mitigating functional decline in this high-risk population.FUNDINGNIH: National Heart, Lung, and Blood Institute (R01-HL146691), National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK123259); American Heart Association (AHA- 24IPA1268813, AHA-22-915561, AHA-24-1195524).
SN - 0021-9738
SN - 1558-8238
ER -