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Introduction: Tissue Na + overload is present in patients receiving hemodialysis (HD) and is associated with cardiovascular mortality. Strategies to actively modify tissue Na + amount in these patients by adjusting the HD regimen have not been evaluated., Methods: In several substudies, including cross-sectional analyses ( n  = 75 patients on HD), a cohort study and a cross-over interventional study ( n  = 10 patients each), we assessed the impact of ultrafiltration (UF) volume, prolongation of dialysis treatment time, and modification of dialysate Na + concentration on tissue Na + content using 23 Na magnetic resonance imaging ( 23 Na-MRI)., Results: In the cross-sectional analysis of our patients on HD, differences in dialysate sodium concentration ([Na + ]) were associated with changes in tissue Na + content, whereas neither UF volume nor HD treatment time affected tissue Na + amount. Skin Na + content was lower in 17 patients on HD, with dialysate [Na + ] of <138 mmol/l compared to 58 patients dialyzing at ≥138 mmol/l (20.7 ± 7.3 vs. 26.0 ± 8.8 arbitrary units [a.u.], P  < 0.05). In the cohort study, intraindividual prolongation of HD treatment time was not associated with a reduction in tissue Na + content. Corresponding to the observational data, intraindividual modification of dialysate [Na + ] from 138 to 142 to 135 mmol/l resulted in concordant changes in skin Na + (24.3 ± 7.6 vs. 26.3 ± 8.0 vs. 20.8 ± 5.6 a.u, P  < 0.05 each), whereas no significant change in muscle Na + occurred., Conclusion: Solely adjustment of dialysate [Na + ] had a reproducible impact on tissue Na + content. 23 Na-MRI could be utilized to monitor the effectiveness of dialysate [Na + ] modifications in randomized-controlled outcome trials., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Sodium can accumulate in the skin at concentrations exceeding serum levels. A high sodium environment can lead to pathogenic T helper 17 cell expansion. Psoriasis is a chronic inflammatory skin disease in which IL-17‒producing T helper 17 cells play a crucial role. In an observational study, we measured skin sodium content in patients with psoriasis and in age-matched healthy controls by Sodium-23 magnetic resonance imaging. Patients with PASI > 5 showed significantly higher sodium and water content in the skin but not in other tissues than those with lower PASI or healthy controls. Skin sodium concentrations measured by Sodium-23 spectroscopy or by atomic absorption spectrometry in ashed-skin biopsies verified the findings with Sodium-23 magnetic resonance imaging. In vitro T helper 17 cell differentiation of naive CD4 + cells from patients with psoriasis markedly induced IL-17A expression under increased sodium chloride concentrations. The imiquimod-induced psoriasis mouse model replicated the human findings. Extracellular tracer Chromium-51-EDTA measurements in imiquimod- and sham-treated skin showed similar extracellular volumes, rendering excessive water of intracellular origin. Chronic genetic IL-17A‒driven psoriasis mouse models underlined the role of IL-17A in dermal sodium accumulation and inflammation. Our data describe skin sodium as a pathophysiological feature of psoriasis, which could open new avenues for its treatment., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic kidney disease (CKD) engenders salt-sensitive hypertension. Whether or not tissue Na + accumulation is increased in CKD patients remains uncertain. How tissue Na + is affected after renal transplantation has not been assessed., Methods: We measured tissue Na + amount in 31 CKD patients (stage 5) and prospectively evaluated tissue Na + content at 3 and 6 months, following living-donor kidney transplantation. Additionally, pre- and post-transplantation data were compared to 31 age- and sex-matched control subjects. 23 Na-magnetic resonance imaging ( 23 Na-MRI) was used to quantify muscle and skin Na + of the lower leg and water distribution was assessed by bioimpedance spectroscopy., Results: Compared to control subjects, CKD patients showed increased muscle (20.7 ± 5.0 vs. 15.5 ± 1.8 arbitrary units [a.u.], P  < 0.001) and skin Na + content (21.4 ± 7.7 vs. 15.0 ± 2.3 a.u., P  < 0.001), whereas plasma Na + concentration did not differ between groups. Restoration of kidney function by successful renal transplantation was accompanied by mobilization of tissue Na + from muscle (20.7 ± 5.0 vs. 16.8 ± 2.8 a.u., P  < 0.001) and skin tissue (21.4 ± 7.7 vs. 16.8 ± 5.2 a.u., P  < 0.001). The reduction of tissue Na + after transplantation was associated with improved renal function, normalization of blood pressure as well as an increase in lymphatic growth-factor concentration (vascular endothelial growth factor C [VEGF-C] 4.5 ± 1.8 vs. 6.7 ± 2.7 ng/ml, P  < 0.01)., Conclusions: Tissue Na + accumulation in predialysis patients with CKD was almost completely reversed to the level of healthy controls after successful kidney transplantation., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Purpose: To quantify the reliability and agreement of sodium ( 23 Na) MRI in calf muscle and skin of healthy subjects and to measure the smallest real difference (SRD) in each., Subjects and Methods: Thirty healthy subjects underwent 23 Na MRI studies of the calf. A scan-rescan protocol was performed the same day and 1 week later. Relative sodium concentration was measured in the calf muscle and skin and compared between studies., Results: A high degree of reliability was confirmed between the scan and rescan tests using linear regression analysis. The Bland-Altman plots indicated high agreement between runs in all regions. The SRD was measured between scans taken the same day and one week later. Correlations were also reported with age, gender and race., Conclusions: Reliability and agreement of 23 Na MRI in the calf muscle and skin show promise for accurately assessing serial changes in patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Long-term elevated blood sugar levels result in tissue matrix compositional changes in patients with diabetes mellitus type 2 (T2DM). We hypothesized that hemodialysis patients with T2DM might accumulate more tissue sodium than control hemodialysis patients. To test this, 23 Na magnetic resonance imaging ( 23 Na MRI) was used to estimate sodium in skin and muscle tissue in hemodialysis patients with or without T2DM. Muscle fat content was estimated by 1 H MRI and tissue sodium content by 23 Na MRI pre- and post-hemodialysis in ten hemodialysis patients with T2DM and in 30 matched control hemodialysis patients. We also assessed body fluid distribution with the Body Composition Monitor. 1 H MRI indicated a tendency to higher muscle fat content in hemodialysis patients with T2DM compared to non-diabetic hemodialysis patients. 23 Na MRI indicated increased sodium content in muscle and skin tissue of hemodialysis patients with T2DM compared to control hemodialysis patients. Multi-frequency bioimpedance was used to estimate extracellular water (ECW), and excess ECW in T2DM hemodialysis patients correlated with HbA1c levels. Sodium mobilization during hemodialysis lowered muscle sodium content post-dialysis to a greater degree in T2DM hemodialysis patients than in control hemodialysis patients. Thus, our findings provide evidence that increased sodium accumulation occurs in hemodialysis patients with T2DM and that impaired serum glucose metabolism is associated with disturbances in tissue sodium and water content., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic inflammatory demyelinating diseases of the CNS typically show a limited lesion size. However, extended lesions may appear with an atypical configuration. Large lesions with a diameter>2cm accompanied by tumor-like edema are entitled "tumefactive" and may occur in multiple sclerosis (MS) and other demyelinating diseases. Historically, differential diagnosis often requires histological analysis. Therefore, advanced imaging techniques are warranted to allow for a precise non-invasive diagnosis. Cerebral sodium ( 23 Na) MRI was recently described as a new method to investigate in vivo sodium accumulation. Indicating extended sodium levels in MS lesions, 23 Na MRI is a promising differential diagnostic tool further elucidating the role of sodium in demyelinating lesions., Methods: Repetitive 23 Na MRI measurements in a MS patient with a tumefactive demyelinating lesion providing insight into the medium-term course of cerebral sodium levels., Results and Conclusion: 23 Na MRI depicts persistent lesional sodium accumulation after anti-inflammatory treatment and provides the opportunity of a non-invasive, in vivo analysis of sodium levels in inflammatory CNS lesions without need for contrast enhancing media. As a result of the extended dimension, tumefactive lesions may have an appropriate size for the analysis of inflammatory demyelination by 23 Na MRI with sufficient resolution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We have previously reported that sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether (23)Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (>60 years) HD patients showed increased sodium and water in skin and muscle and lower VEGF-C levels compared with age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content compared with patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/l; high VEGF-C: 4.1 ng/ml and skin sodium: 18.2 mmol/l). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard end points could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.

Background: Prior studies found that some groups have lower genetic consent rates than others. Participant consent for genetic studies enables randomized trials to examine effects of interventions compared to control in participants with different genotypes., Methods: Unadjusted and multivariate associations between genetic consent rates and participant, study, and consent characteristics in 9573 participants approached for genetics consent in the multicenter Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which used a layered genetics consent., Results: Eighty-nine percent of eligible participants consented to genetic studies ("Any Consent") and 64.7% consented to studies of any genes by any investigator ("Full Consent"), with similar rates in randomized groups. Controlling for multiple characteristics, African-Americans had lower consent rates than others (Any Consent Odds Ratio, OR = 0.62, p = 0.0004; Full Consent OR = 0.67, p < 0.0001). Those with high school or higher education level had higher rates than less than high school graduates (Full Consent ORs 1.41-1.69, p-values < 0.0001). Consent rates were lower when genetics consent was separate from the main trial consent on the same day (Any Consent OR 0.30; Full Consent OR 0.52, p values < 0.0001) or on a subsequent day (Any Consent OR 0.70, p = 0.0022; Full Consent OR 0.76, p = 0.0002)., Conclusion: High rates of consent for genetic studies can be obtained in complex randomized trials, with lower consent rates in African-Americans, in participants with less than high-school education, and for sharing samples with other investigators. A genetics consent separated from the main trial consent was associated with lower consent rates., (Published by Elsevier Inc.)