Dapagliflozin attenuates progression from prefrailty to frailty in patients with hypertension and chronic kidney disease

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Abstract

BACKGROUND Chronic 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).METHODS We 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.RESULTS A 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).CONCLUSION In 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.FUNDING NIH: 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).

Authors

Pasquale Mone, Davide Viggiano, Antonella Pansini, Maria Virginia Soldovieri, Giada Sabatelli, Valeria Visco, Gaetano Macina, Eugenio Boccalone, Michele Ciccarelli, Giuseppe Martinelli, Marco Di Mauro, Carmine Vecchione, Maria Morgante, Fahimeh Varzideh, Germano Guerra, Gaetano Santulli