Effects of dapagliflozin on vascular calcification among patients with chronic kidney disease without diabetes: a randomized controlled trial
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Abstract
Background: Chronic kidney disease (CKD) impairs the metabolic pathways and renal regulation, induces the release of proinflammatory cytokines and leads to endothelial and vascular smooth muscle cell injury. This injury results in subsequently increased vascular stiffness and calcification. Sodium glucose co-transporter 2 inhibitors (SGLT2i) have been proved to be cardio- and renoprotective. The outlying mechanism involves not only lowering glucose but is also hemodynamic-related and alters cytokine and adipokine production. This could explain the desired result of improved vascular stiffness, vascular calcification or inflammation.
Methods: This study was performed as a single center, prospective, double-blinded, randomized placebo-controlled trial among nondiabetic patients with CKD stages 3-4 in Vajira Hospital between July and October 2019. They were randomized to receive dapagliflozin 10 mg daily or placebo for 4 months. The primary outcomes were differences in vascular calcification measured by ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI). The secondary outcomes were change in inflammatory markers, eGFR, albuminuria and other adverse events.
Results: Fifty-seven patients were enrolled in the study, including 29 patients in the dapagliflozin group and 28 patients in the placebo group. Patients in the dapagliflozin group showed no improvement in vascular stiffness (right ABI; dapagliflozin 1.01 0.13 vs. placebo 1.02 0.15, p = 0.847, left ABI; dapagliflozin 0.99 0.14 vs. placebo 1.02 0.10, p = 0.244) nor in vascular calcification (right CAVI; dapagliflozin 9.06 1.77 vs. placebo 7.81 2.18, p = 0.021, left CAVI; dapagliflozin 8.96 1.65 vs. placebo 9.03 3.40, p = 0.913). Patients in the dapagliflozin group presented no significant change in inflammatory markers while the control group exhibited increased inflammatory markers. No serious adverse effect related to dapagliflozin was found in either group.
Conclusion: Beneficial effects of dapagliflozin on vascular stiffness or vascular calcification were inconclusive in this study. However, dapagliflozin could have significantly attenuated the inflammatory process which was evidently aggravated in the placebo group.
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