Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial and serum uromodulin. Among these, uromodulin modulates renal sodium handling through the regulation of tubular sodium transporters that reabsorb sodium and are targeted by diuretics, such as the loop diuretic–sensitive Na⁺-K⁺-2Cl⁻ cotransporter type 2 (NKCC2) and the thiazide-sensitive Na⁺/Cl⁻ cotransporter (NCC). Given these roles, the contribution of uromodulin to sodium-sensitive hypertension has been proposed. However, recent studies in humans suggest a more complex interaction between dietary sodium intake, uromodulin and blood pressure. This review presents an updated overview of the uromodulin's biology and its various roles, and focuses on the interaction between uromodulin and sodium-sensitive hypertension.

Intradialytic hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137 mEq/L) compared with standard (140 mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. In this randomized, single-blind, crossover study, 29 patients with IDH underwent four hemodialysis sessions with low (137 mEq/L) followed by four sessions with standard (140 mEq/L) dialysate sodium, or vice versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. Mean 48-h systolic/diastolic BP (SBP/DBP) were significantly lower with low compared with standard dialysate sodium concentration (137.6 ± 17.0/81.4 ± 13.7 mmHg with low vs 142.9 ± 14.5/84.0 ± 13.9 mmHg with standard dialysate sodium, P = .005/P = .007, respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3 ± 22.3/91.2 ± 15.1 mmHg with low vs 166.6 ± 17.3/94.5 ± 14.9 mmHg with standard dialysate sodium, P < .001/P = .134, respectively) and intradialytic (141.4 ± 18.0/85.0 ± 13.4 mmHg with low vs 147.5 ± 13.6/88.1 ± 12.5 mmHg with standard dialysate sodium, P = .034/P = .013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B lines were also significantly decreased with low dialysate sodium. Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH. ClinicalTrials.gov study number NCT05430438.

The Fontan procedure is a definitive surgical approach for complex cardiac malformations, redirecting systemic venous blood into the pulmonary circulation through a staged repair that separates systemic and pulmonary venous returns in the absence of a subpulmonary ventricle. The ensuing unique hemodynamic conditions compromise the endothelial function both in the pulmonary and the systemic circulation. The underlying pathophysiological mechanisms, although distinct within each vascular bed, are interrelated and may collectively contribute to progressive end-organ dysfunction, ultimately accounting for the significant morbidity burden in Fontan patients. This review provides an overview of the current knowledge on the pathophysiology of pulmonary and systemic vasculopathy in Fontan circulation, with particular emphasis on the interplay between endothelial dysfunction and adverse clinical outcomes. Remaining gaps in knowledge and directions of future research are also discussed. Graphical abstract

Endothelial dysfunction is associated with increased cardiovascular risk in individuals with autoimmune diseases. This is a systematic review and meta-analysis of studies assessing endothelial function with functional methods in order to examine the differences on endothelium in children with rheumatic diseases versus controls. Literature search involved PubMed and Scopus databases from inception to February 2024 and manual search of article references. Studies assessing endothelial function by all available functional methods were eligible. Quality of studies was evaluated via Newcastle-Ottawa scale. Twenty-four studies (880 children with rheumatic diseases, 784 controls) were included in meta-analysis. In pooled analysis, a pronounced endothelial dysfunction was observed among patients with pediatric rheumatic diseases compared to controls (SMD: -0.74, 95%CI -1.10 to -0.39) but with high heterogeneity (I² = 91%, p < 0.001); this was also confirmed in the sensitivity analysis including only high-quality studies (SMD: -0.83, 95%CI -1.20 to -0.46). In subgroup analyses according to type of rheumatic disease, a significantly impaired endothelial function was showed for patients with juvenile idiopathic arthritis (SMD: -1.05, 95%CI -1.84 to -0.25), vasculitis (SMD: -0.74, 95%CI -1.11 to -0.37) and juvenile systemic sclerosis (SMD -2.48, 95%CI -4.34 to -0.61). Patients with pediatric rheumatic diseases show an impaired endothelial function. Future studies are needed to elucidate whether vascular endothelial dysfunction is involved in high cardiovascular risk of children with rheumatic diseases. CRD42023413799.

Introduction: Cardiac arrhythmias are the most common cause of death in hemodialysis. Autonomic dysfunction plays a central role in this arrhythmogenic background. Previous studies on hemodialysis-related changes in heart rate variability (HRV) give contradictory results. This study investigated HRV indices both at rest and in response to physical and mental stimulation maneuvers at multiple time-points around and during the hemodialysis procedure. Methods: Autonomic function was assessed by linear and nonlinear HRV indices at predialysis, during dialysis (3 equal time-periods), postdialysis, and on the nondialysis day in 36 hemodialysis patients. Continuous measurement of beat-by-beat heart rate was recorded with Finometer-PRO (The Netherlands) at rest and after orthostatic, sit-to-stand, handgrip, and mental-arithmetic test. Results: The RMSSD, SD1, and SD2 indices significantly increased during dialysis (early-HD, mid-HD, late-HD periods) compared with the predialysis levels (p < 0.05) and returned to baseline postdialysis (RMSSD: 54.39 ± 83.73 vs. 137.98 ± 109.53* vs. 119.85 ± 97.34* vs. 144.47 ± 88.74* vs. 85.82 ± 121.43msec, *p < 0.05 vs. predialysis and postdialysis). No differences were detected in the above indices between the predialysis and nondialysis day. However, postdialysis, the HRV responses to orthostatic and sit-to-stand tests were more exaggerated than in the predialysis measurements (p < 0.05). The HRV responses both at resting and physical tests in the nondialysis day were similar to the predialysis levels. HRV indices in the mental arithmetic test during hemodialysis were much higher than at the nondialysis day (RMSSD: 77.05 [180.41] versus 19.75 [105.47] msec; p = 0.031). Conclusions: Hemodialysis causes marked changes in the autonomic function. Resting HRV indices return to baseline postdialysis, but HRV responses to physical stress remain exaggerated and return to baseline on the nondialysis day. Detecting patients with significant autonomic dysfunction may help towards reduction of arrhythmia risk through individualized approaches.