Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.

The first observation of osmotically neutral sodium accumulation in the myocardial interstitium

The aim of this study was the detection and quantification of the Na+ depositions in the extracellular matrix of myocardial tissue, which are suggested to be bound by negatively charged glycosaminoglycan (GAG) structures. The presented experimental results are based on high resolution X-ray fluorescence (XRF) spectromicroscopy technique used to perform a comparative analysis of sodium containment in intracellular and interstitial spaces of cardiac tissues taken from animals selected by low and high sodium intake rates. The experimental results obtained show that high sodium daily intake can result in a remarkable increase of sodium content in the myocardial interstitium.

Mitigating salt accumulation in recycled brewery effluent through the integration of water treatment, agriculture and aquaculture

Water scarcity in South Africa, and globally, presents challenges for industries. It is imperative to develop responsible water use, such as recycling and reusing wastewater from food processing industries such as breweries. The Ibhayi Brewery (SAB Ltd) employs a combination of sustainable treatment processes that include anaerobic digestion (AD), primary facultative ponds (PFP), high rate algal ponds (HRAP) and constructed wetlands (CW) to treat brewery effluent on an experimental scale. The constituent concentrations of these experimentally treated effluents are within the ranges prescribed by local regulations to allow for potential downstream use in agriculture and aquaculture. However, the sodium content in this treated effluent, which originates from upstream cleaning agents and pH control at the onsite effluent treatment facility, is a constraint to the downstream use of brewery effluent. This study addresses the salt problem, by investigating the potential of either reducing/eliminating salt addition at source, or developing alternative techniques for downstream agriculture to mitigate the effects of salt accumulation caused by irrigation with brewery effluent. Four salt-tolerant test crops; Swiss chard (Beta vulgaris), saltbush (Atriplex nummularia), Salicornia meyeriana and sorghum (Sorghum bicolor), grew efficiently in brewery effluent irrigated soils but did not stop sodium accumulation in the growth medium. Swiss chard had the best growth with a wet biomass accumulation of 8,173 g m-2, due to the plant’s ability to tolerate saline conditions and continuous cropping. Crop rotation, to limit effects of nutrient depletion in soil, had no significant effect on plant growth suggesting soils were adequately able to provide micro-nutrients in the short-term. Prolonged irrigation with brewery effluent can lead to sodium accumulation in the soil, which was successfully controlled through the addition of soil amendments (gypsum and Trichoderma cultures). These reduced soil sodium from a potentially limiting level of 1,398 mg L-1 to the acceptable levels of 240 mg L-1 and 353 mg L-1 respectively, mainly through leaching. However only Trichoderma improved Swiss chard production to 11,238 g m-2. While crop rotation in this work did not contribute to mitigating the problem of salt accumulation, soil amended with Trichoderma appears to be a potential solution when brewery effluent is reused in agriculture. In an alternative to soil cultivation, CWs were trialled with no significant differences in the sodium concentration of brewery effluent treated along a 15 m lateral flow CW, which could be attributed to evapotranspiration. This was notably accompanied by a desirable 95.21% decrease in ammonia from inlet to outlet resulting in significant improvement in water quality for reuse in aquaculture where ammonia levels are important limiting constraints. While CWs remain a suitable brewery effluent treatment solution, this technology requires additional modelling and optimisation in order to mitigate the problem of salt accumulation in the reuse of treated brewery effluent in agriculture and aquaculture. This research demonstrates the baseline information for such modelling and optimisation. African catfish (Clarias gariepinus) grew in CW treated brewery effluent; however, this growth was moderate at 0.92% bw day-1, whereas Mozambique tilapia (Oreochromis mossambicus) were shown to be unsuited to growth in this system and lost weight with an average specific growth rate (SGR) of -0.98% bw day-1; and both fish species presenting with health related concerns. Hardy fish species such as African catfish can be cultured in brewery effluent, but with risk involved. This was a preliminary study to develop parameters for future dimensional analysis modelling to allow optimisation of the CW, based on nutrient removal rates obtained which will allow for improved downstream aquaculture by reducing or eliminating risks presented in this study. This work has also contributed to a foundation for the development of guidelines that use a risk-based approach for water use in aquaculture. Alternatives to the current in place cleaning agents were considered to mitigate the effects of salt accumulation. Sodium is introduced into the effluent via the use of sodium hydroxide and sodium chlorite for cleaning and disinfection in the brewery, as well as through effluent pH adjustment in the AD plant. The widespread use of outdated legacy cleaning systems and pH adjustment regimes is entrenched in the brewery standard operating procedures (SOP). A cost-benefit analysis (CBA) demonstrated that a change of cleaning and disinfecting regimes to hydrogen peroxide in the brewery, and magnesium hydroxide pH adjustment in the effluent treatment plant addresses the sodium issue upstream in the brewery practically eliminating sodium from the effluent. In addition, a life cycle analysis (LCA) was carried out to assess the environmental impacts associated with the alternative cleaning and pH adjustment scenarios. The LCA showed that electricity consumption during use phase of the chemicals for respective purposes, as well as their production activities were major contributors to the significant environmental impact categories that were assessed. The cleaning scenario employing the use of hydrogen peroxide for both cleaning and disinfection was found to be the most environmentally sustainable. This was attributed to the reduced number of chemicals used compared to the other cleaning scenarios. Dolomitic lime was the pH adjustment alternative with the lowest average environmental impact; but, however, had a higher impact on freshwater eutrophication which is of major concern if the effluent will be reused for irrigation. Magnesium hydroxide was therefore considered to be the better option as a sodium hydroxide alternative for pH adjustment. This mitigates salt accumulation, making treated brewery effluent suitable for reuse in high value downstream agriculture and aquaculture, while employing more environmentally sustainable technologies. Notably, this converts brewery effluent from a financial liability to Ibhayi Brewery, into a product containing water and nutrients that generate income, improve food security, and can create employment in downstream agriculture and aquaculture in a sustainable manner.

Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI

Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium (23Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton (1H) and 23Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD.

The first observation of osmotically neutral sodium accumulation in the myocardial interstitium

The aim of this study was the detection and quantification of the Na+ depositions in the extracellular matrix of myocardial tissue, which are suggested to be bound by negatively charged glycosaminoglycan (GAG) structures. The presented experimental results are based on high resolution X-ray fluorescence (XRF) spectromicroscopy technique used to perform a comparative analysis of sodium containment in intracellular and interstitial spaces of cardiac tissues taken from animals selected by low and high sodium intake rates. The experimental results obtained show that high sodium daily intake can result in a remarkable increase of sodium concentration in the myocardial interstitium.

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.

Sodium accumulation in breast cancer predicts malignancy and treatment response

Breast cancer is the leading cause of cancer-related death in women worldwide. Development of novel noninvasive diagnostic and predictive pathophysiological biomarkers would represent a significant clinical improvement. Here, we explored the utility of non-invasive 23Na MRI to profile tumour physiology using preclinical mouse models of breast cancer. We establish that tissue Na+ concentration ([Na+]) is elevated vs non-tumour regions across multiple different tumour models. Ex vivo SBFI fluorescence imaging corroborated that this elevation in tumour [Na+] is due to increased intracellular [Na+]. Effective treatment with cytotoxic chemotherapy reduced tumour tissue [Na+], but was not detected by 1H diffusion-weighted imaging (DWI). Moreover, combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared to either parameter alone. Quantification of breast tumour tissue [Na+] using 23Na MRI thus represents a novel, accurate, non-invasive diagnostic and predictive imaging biomarker.