Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?

Background: Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23 Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. Methods: We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23 Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. Results: There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23–37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22–35] mmol/L), P =0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19–26] mmol/L), P =0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P =0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium ( P =0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% ( P =0.03). Conclusions: We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23 Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03004547.

Total Body Sodium Balance in Chronic Kidney Disease

Excess sodium intake is a leading but modifiable risk factor for mortality, with implications on hypertension, inflammation, cardiovascular disease, and chronic kidney disease (CKD). This review will focus mainly on the limitations of current measurement methods of sodium balance particularly in patients with CKD who have complex sodium physiology. The suboptimal accuracy of sodium intake and excretion measurement is seemingly more marked with the evolving understanding of tissue (skin and muscle) sodium. Tissue sodium represents an extrarenal influence on sodium homeostasis with demonstrated clinical associations of hypertension and inflammation. Measurement of tissue sodium has been largely unexplored in patients with CKD. Development and adoption of more comprehensive and dynamic assessment of body sodium balance is needed to better understand sodium physiology in the human body and explore therapeutic strategies to improve the clinical outcomes in the CKD population.

No Escape: The Influence of Substrate Sodium on Plant Growth and Tissue Sodium Responses

As an essential micronutrient for many organisms, sodium plays an important role in ecological and evolutionary dynamics. Although plants mediate trophic fluxes of sodium, from substrates to higher trophic levels, we know relatively little about plants’ comparative growth and sodium accumulation responses to variation in substrate sodium. We carried out a systematic review to examine how plants respond to variation in substrate sodium concentrations. We compared growth and tissue-sodium responses among 107 populations (67 species in 20 plant families), broadly expanding beyond the agricultural and model taxa for which several generalizations previously have been made. We hypothesized a priori response models for each population’s growth and sodium accumulation responses as a function of increasing substrate NaCl. We used BIC to choose the best model. Additionally, using a phylogenetic signal analysis, we tested for phylogenetic patterning of growth and sodium accumulation responses across plant taxa. The influence of substrate sodium on growth differed across taxa, with most populations experiencing detrimental effects at high concentrations. Irrespective of growth response, tissue concentrations of sodium for most taxa increased as sodium concentrations in the substrate increased. We found no strong associations between growth and types of sodium accumulation responses across taxa. Our phylogenetic signal analyses found that evolutionary history helps predict the distribution of total plant growth responses across the phylogeny, but not sodium accumulation responses. Our study suggests that saltier plants in saltier soils may prove to be a broadly general pattern for sodium across plant taxa. Regardless of growth responses, sodium accumulation mostly followed an increasing trend and did not have any evident association with growth responses as substrate sodium levels increased. Finally, plant adaptations to substrate sodium vary with a degree of phylogenetic conservatism.

Tissue Sodium Concentration within White Matter Correlates with the Extent of Small Vessel Disease

Introduction: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. Methodology: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. Results: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. Conclusion: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification.