BACKGROUND: Arterial stiffness is a strong predictor of death and cardiovascular (CV) events in hemodialysis patients. Only few studies tested interventions aiming to improve arterial stiffness in this population. This study examines the effect of dry-weight reduction with a standardized lung-ultrasound-guided strategy on ambulatory aortic blood pressure (BP) and arterial stiffness parameters in hemodialysis.METHODS: Seventy-one clinically euvolemic hemodialysis patients with hypertension, were included in this single-blind randomized clinical-trial. Patients were randomized in the active group (n = 35), following dry-weight reduction guided by the total number of US-B lines before a mid-week dialysis session and the control group (n = 36), following standard treatment. Patients underwent office evaluation of arterial stiffness and 48-h ABPM to capture ambulatory central systolic (cSBP) and diastolic BP (cDBP) and arterial stiffness indexes at baseline and after 8-weeks.RESULTS: US-B lines decreased in the active and slightly increased in the control group (p < 0.001) during follow-up. Office-pulse-wave-velocity (PWV) decreased from baseline to study-end only in the active group, resulting in significant between-group differences (- 0.25 ± 0.71 vs 0.20 ± 1.18 m/s p = 0.037). Reduction in 48-h-cSBP (- 6.30 ± 8.90 vs - 0.50 ± 12.46; p = 0.027) was greater and in cDBP (- 3.85 ± 6.61 vs - 0.63 ± 8.36; p = 0.077) marginally greater in the active compared to control group. 48-h-central-pulse-pressure (cPP, 41.51 ± 9.63 vs 39.06 ± 9.61 mmHg; p = 0.004) and 48-h-PWV (9.30 ± 2.00 vs 9.08 ± 2.04 m/s p = 0.032) were significantly reduced during follow-up in the active group and were unchanged in controls, resulting in significant between-group differences. In contrast, 48-h-AIx and AIx(75) were not different between the two groups.CONCLUSION: Lung-ultrasound-guided dry-weight reduction decreased ambulatory aortic-BP and ambulatory or office-PWV, but not ambulatory-AIx(75). These results suggest that dry-weight reduction is an important treatment approach to improve these cardiovascular risk factors in hemodialysis.