Salt Loading Research Articles

Catecholaminergic RVLM C1 neurons mediates heart failure decompensation and mortality during salt loading

Heart failure (HF) is a complex clinical syndrome affecting over 37 million people worldwide. Although advances in medical therapy have significantly improve HF condition, morbidity and mortality rate are still high and global prevalence is continuously rising. Common clinical features of HF include cardiac sympathoexcitation and disordered breathing, which are strongly associated with poor survival of HF patients. Importantly, we have previously shown that brainstem pre‐sympathetic neurons (C1) from the rostral ventrolateral medulla (RVLM), play a key role in sympathetic regulation in HF. However, the role played by RVLM‐C1 neurons during heart failure decompensation is totally unknown. Accordingly, we aimed to determine the contribution of RVLM‐C1 neurons on survival during HF decompensation. Adult male Sprague‐Dawley rats underwent volume overload induce non‐ischemic HF. After two weeks, anti‐dopamine β‐hydroxylase‐saporin toxin (DβH‐SAP: 2.5ng/150nl; or saline) was bilaterally injected into RVLM to ablate C1 neurons. Animals were then expose to high salt diet (3% Na+ in food and 2% Na+ in water) for 3 weeks to induce transition from compensated to decompensated HF state. At 6 weeks post‐HF induction, echocardiography, cardiac autonomic function, breathing function, blood pressure, and mortality were assessed. Compared to normal chow fed HF animals, HF+Na+ rats displayed an increased cardiac index (15.1 ± 0.6 vs. 18.5 ± 1.3 ml/min/100cm2, HF vs. HF+Na+, respectively) and cardiac sympathetic tone (∆HR to propranolol: 8.7 ± 3.1 vs. 23.4 ± 2.5 bpm, HF vs. HF+Na+, respectively). Furthermore, HF+Na+ animals showed a further increase in the incidence of breathing disorders compared to HF (apnea‐hypopnea index: 8.1 ± 0.6 vs. 12.5 ± 2.1 events/hr, HF vs. HF+Na+, respectively). Lastly, salt loading results in marked decompensation in HF rats being the outcome a significant increase in mortality risk (survival: 100% vs. 10% HF vs. HF+Na+, respectively). We found that partial ablation of RVLM C1 neurons in HF+Na+ prevented further deterioration in cardiac autonomic function and breathing disorders and markedly improved survival in HF rats that underwent salt loading (survival: 10% vs. 75% HF+Na+ vs. HF+DβH‐SAP+Na+, respectively). Our results strongly support the role for RVLM C1 neurons in HF decompensation during salt loading and suggest that RVLM C1 may act as a key nodal point mediating salt induced cardiorespiratory distress, decompensation and mortality in HF.

Does G protein‐coupled Estrogen Receptor 1 Contribute to Cisplatin‐induced Acute Kidney Injury?

Cisplatin (Cp) is an effective chemotherapeutic agent used to treat a wide variety of malignancies. Nephrotoxicity is the dose‐limiting side effect of Cp. Acute kidney injury (AKI) following Cp administration is multi‐factorial, involving cellular toxicity, inflammation and proximal tubular injury. Recent evidence points to renal protective actions of G protein‐coupled estrogen receptor 1 (GPER1) in nephropathies evoked by salt loading, hypertension, methotrexate and ischemia reperfusion. Additionally, GPER1 abundance increases after renal ischemia reperfusion injury. However, the involvement of GPER1 signaling in Cp‐induced nephrotoxicity remains unclear. Therefore, this study was designed to test whether genetic deletion of GPER1 exacerbates Cp‐induced AKI in male mice. We subjected 14‐16 weeks‐old male mice homozygous (homo), heterozygous (het) for GPER1 gene and wild‐type (WT) littermates to Cp or saline injections and assessed markers for renal injury on the third day after injections. Specifically, we measured serum creatinine (sCr), urea, neutrophil gelatinase‐associated lipocalin (NGAL), histological indexes of renal tubular injury and abundance of kidney injury molecule‐1 (KIM‐1) and NGAL in the kidney. We determined also serum levels of proinflammatory markers in saline and Cp‐treated mice. A rise sCr was evident in all Cp‐treated mice, compared to saline‐treated mice (WT: 1.72±0.24 vs. 0.12±0.01; het: 1.14±0.30 vs. 0.12±0.01; homo: 1.28±0.31 vs. 0.14±0.01 mg/dl, p<0.0001, p=0.0149, p=0.0028, respectively, n=9‐13). Serum urea and NGAL levels followed the same pattern as sCr. Cp‐induced AKI resulted in comparable histological evidence of injury in all genotypes. Kidney KIM‐1 abundance was higher in saline‐treated homo mice, compared to corresponding WT mice (14.00±2.30 vs. 7.62±0.70 AU, respectively, p=0.0188, n=8, 13). Kidney KIM‐1 abundance was markedly upregulated in response to Cp in all groups, however, no genotypic differences were observed in kidney KIM‐1 in Cp‐treated mice. Cytokine panel assessment demonstrated increased circulating levels of interleukin‐2 (IL‐2), IL‐5, IL‐10 and tumor necrosis factor‐a in Cp‐treated mice. GPER1 deletion lowered plasma IL‐12p70 (p=0.0176). Given the protective role of heme oxygenase‐1 (HO‐1) in Cp‐mediated cell injury, we also investigated genotypic differences in renal HO‐1 abundance. WT and homo mice showed greater renal HO‐1 abundance in response to Cp. Interestingly, renal HO‐1 abundance was lower in Cp‐treated homo, compared to Cp‐treated WT mice (65.74±6.70 vs. 87.83±5.11 AU, respectively, p=0.0083, n=8, 13), despite the lack of genotypic differences in kidney HO‐1 levels in saline‐treated mice. Overall, we demonstrate that GPER1 homo, het male mice and WT littermates elicit comparable renal injury in response to Cp. We show also that GPER1 deletion diminishes HO‐1 induction in response Cp, suggesting that GPER1 may play a permissive role for HO‐1 cytoprotective actions in AKI. GPER1‐induced regulation of HO‐1 after Cp treatment may offer a novel therapeutic target for the treatment of AKI.

Adaptation to High‐Salt Diet Requires H,K‐ATPase Type 2 Dependent NaCl Secretion

IntroductionThe kidney controls the extracellular volume and the blood pressure because of its ability to excrete efficiently Na+ and Cl‐ ions. These last decades in Western countries the consumption of salt has dramatically increase and the question arises as to how the kidney adapts to this chronic situation. Up to now, the mechanisms described to excrete a large load of salt consist in the inhibition of Na+ reabsorption all along the nephron. We have recently identified a novel pathway that mediates the secretion of Na+ in the collecting duct (Morla, L. et al. 2016). This system involves A‐type intercalated cells (AIC), NKCC1 and the H,K‐ATPase type 2 (HKA2), which is known to be able to transport Na+. Here, we investigated the role of HKA2 in NaCl renal secretion, as well as the physiological relevance of this secretory pathway in vivo, in response to salt load.Material and MethodsC57BL6J mice wild type or knockout for the Atp12a gene (HKA2‐KO) were used and placed under a control (NS) or high‐Na+ (HS) diets for 3 days. Outer medullary collecting ducts (OMCD) of WT mice under NS or HS were isolated for RNAseq and RT‐PCR analysis. Type A intercalated cells were isolated by FACS (following labelling with c‐kit antibodies) from WT mice under NS or HS for RT‐PCR analysis. The mice were also placed in metabolic cages for measurements of physiological parameters (food and water intakes, urine excretion, plasma parameters). Blood pressure was assessed by tail‐cuffed measurement.ResultsThe RNA seq analysis of OMCD revealed that, as expected, genes involved in Na+ reabsorption (ENaCa, SGK) are downregulated. However, we also observed that HS diet also leads to an increased expression of the Atp12a gene that encodes for the catalytic subunit of the HKA2 both in OMCD and ICA. To understand the role of the HKA2, we placed the HKA2‐KO mice under high‐salt diet and observed that those mice exhibit a salt loosing phenotype with low blood pressure that is due to a stronger down‐regulation of NKCC2 than in WT in the same context. Therefore, the absence of HKA2 is over‐compensated by the inhibition of a reabsorption pathway.ConclusionAltogether, these results demonstrate that the secretion of Na+ in OMCD is stimulated in response to high salt intake.

Morphological analysis of the retina in salt-loaded KK-Ay mice, obese and type 2 diabetic model

Retinopathy, one of the microvascular complications in diabetes, can cause blindness. Salt-loading is known to exacerbate microvascular damage and may affect retinopathy. In this study, we investigated the effect of salt loading on early lesions of diabetic retinopathy. Male C57BL/6 and KK-Ay mice were salt-loaded with 1% sodium chloride (NaCl)-containing drinking water for 12 weeks. In addition, to determine the effects of high fat and high sucrose, a high fat/high sucrose diet was also fed to the 1% NaCl-loaded group of mice of both strains. Retinal thickness was measured at an arbitrary location from the optic nerve disc, and thinning of the retina was observed in KK-Ay mice compared to C57BL/6 mice. Salt-loading caused retinal thinning in C57BL/6 mice, but not in KK-Ay mice. In KK-Ay mice, the effect of salt-loading may have been masked by the effects of obesity and diabetic status during this experimental period. There was also a small effect of QF on the retina, suggesting that dietary components other than salt loading may affect retinopathy.

High Dietary Salt Intake Is Associated With Histone Methylation in Salt-Sensitive Individuals

BackgroundHigh salt diet is one of the important risk factors of hypertension and cardiovascular diseases. Increasingly strong evidence supports epigenetic mechanisms' significant role in hypertension. We aimed to explore associations of epigenetics with high salt diet, salt sensitivity (SS), and SS hypertension.MethodsWe conducted a dietary intervention study of chronic salt loading in 339 subjects from northern China in 2004 and divided the subjects into different salt sensitivity phenotypes. A total of 152 participants were randomly selected from the same cohort for follow-up in 2018 to explore the effect of a high-salt diet on serum monomethylation of H3K4 (H3K4me1), histone methyltransferase Set7, and lysine-specific demethylase 1 (LSD-1).ResultsAmong SS individuals, the blood pressure (SBP: 140.8 vs. 132.9 mmHg; MAP: 104.2 vs. 98.7 mmHg) and prevalence of hypertension (58.8 vs. 32.8%) were significantly higher in high salt (HS) diet group than in normal salt (NS) diet group, but not in the salt-resistant (SR) individuals (P > 0.05). Serum H3K4me1 level (287.3 vs. 179.7 pg/ml, P < 0.05) significantly increased in HS group of SS individuals, but not in SR individuals. We found daily salt intake in SS individuals was positively correlated with serum H3K4me1 (r = 0.322, P = 0.005) and Set7 (r = 0.340, P = 0.005) levels after adjusting for age and gender, but not with LSD-1 (r = −0.137, P = 0.251). In addition, positive correlation between the serum H3K4me1 level and Set7 level (r = 0.326, P = 0.007) was also found in SS individuals. These correlations were not evident in SR individuals.ConclusionOur study indicates that high salt diet increases the serum H3K4me1 and Set7 levels in SS individuals.

Simulating salinity transport in High-Desert landscapes using APEX-MODFLOW-Salt

Salt pollution in semi-arid landscapes is detrimental to food production, ecosystem biodiversity, soil health, and water supply. High-desert watersheds, due to natural salt deposits, are a key source of salinity in river basins. Although studies have aimed at simulating and estimating salt movement in these landscapes, approaches have relied on lumped, statistical procedures that treat salt as a conservative solute rather than a collection of reactive salt ions. These approaches are limited in quantifying the source, transport, and fate of salt under both historical and future conditions. This study presents a new physically-based spatially distributed salinity transport model for watershed systems of various spatial scales. The model combines the watershed model APEX, the groundwater model MODFLOW, the groundwater reactive transport model RT3D, and a new salinity module to simulate the fate and reactive transport of eight major ions (SO42-, Cl-, CO32–, HCO3–, Ca2+, Na+, Mg2+, K+) in soils, aquifers, and streams of a complex watershed system. Salt loading to streams occurs via surface runoff, erosion runoff, soil lateral flow, and groundwater discharge. The linked APEX-MODFLOW-Salt model is applied to the Price River Watershed (PRW) (4,886 km2), Utah, USA, a portion of the salinity-laden Upper Colorado River Basin, to estimate spatio-temporal loadings from the various hydrologic pathways and total salt yield in the river during 1995–2015. Results indicate that the vast majority (89%) of dissolved salt in the Price River and its tributaries is loaded by groundwater, and that more than half of the salt is in the form of sulfate (SO4). Erosion runoff due to rainfall events is responsible for only 1.5% of total salt yield in the PRW. Total annual dissolved salt loading from the PRW through its outlet is approximately 63,500 Mg. From the results, we conclude that managing salinity in the PRW may need to focus principally on groundwater and its sources.

Investigation of dielectric properties of PEGMEA/PEGDA nanocomposites containing in-situ photochemically prepared ε-Fe2O3 nanocrystals

Photopolymerization of PEGMEA/PEGDA monomer mixture consisting of FeCl3.6H2O metallic salt was performed using a Type I photoinitiator, namely 2-Hydroxy-4′-(2-hydroxyethyl)-2-methyl propane (Irgacure 2959). Herein, we report the easy and one-step in-situ synthesis method of a rare ε-Fe2O3 polymorph in a polymer matrix with different concentrations of Fe3+ salt. Thermal gravimetric analyses of the nanocomposites indicate an increase of char yield depending on both the synthesized nanoparticle concentration and good distribution of Nps. SEM images are also proof of formation of ε-Fe2O3 Nps in polymer matrix. The obtained results indicate 4 and 20%w/w Fe3+ salt loading in the formulations resulted in higher char yield. Dielectric spectroscopy analysis and calculated glass transition temperatures show that there may be a critical ratio between 4 and 8% in the A1 and A2 samples, in comparison with the sample A3 which is the nanocomposite with 20% ε-Fe2O3 Nps. A3 probably has excess free charges contributing to additional conduction.

The microbiota-gut-kidney axis mediates host osmoregulation in a small desert mammal

Regulating sodium and water balances is crucial for survival of small, desert mammals. Studies demonstrate that the gut microbiota and their metabolites are involved in host energy homeostasis, but little is known on the interactions among salt loading, gut microbiota, and osmoregulation. The aim of this study was to fill this gap. Mongolian gerbils (Meriones unguiculatus) were offered drinking water (Con) and either water containing moderate (4%, MS) or high NaCl (8%, HS) ad libitum. Intake of HS reduced α diversity of the microbial community and, at the genus level, reduced the relative abundances of Rikenella and Christensenella but increased Atopobium. To confirm the function of gut microbiota in host osmoregulation, we transplanted caecal microbiota in HS gerbils. To cope with salt loading, the gerbils concentrated urine, resulting in negative energy balance and systemic inflammation. The HS gerbils increased hypothalamic arginine vasopressin and intestinal and renal aquaporin 2 to support water retention, and reduced intestinal and renal epithelial sodium channel α to promote sodium excretion. However, HS gerbils with caecal microbiota transplant (CMT) from Con donors maintained energy balance and osmoregulation, and had a much reduced systemic inflammation. Further, CMT from Con donors to HS recipients reshaped the gut microbiota, particularly by reducing Parabacteroides distasonis and Prevotella copri, and increasing Lactobacillus reuteri abundances, with a resulting increase in bacterial metabolites such as butyrate. These findings highlight a vital role of the microbiota-gut-kidney axis in mediating salt-related osmoregulation, allowing small mammals to adapt to high salt loads in a desert habitat.

Salt Removal through Residue-Filled Cut-Soiler Simulated Preferential Shallow Subsurface Drainage Improves Yield, Quality and Plant Water Relations of Mustard (Brassica juncea L.)

Soil salinity and the use of saline groundwater are two major constraints in crop production, which covers a ~1.0 billion ha area of arid and semi-arid regions. The improved drainage function of soil can modify the salty growing environment for higher agricultural production. The present study evaluated the effectiveness of cut-soiler-constructed rice residue-filled preferential shallow subsurface drainage (PSSD) to improve the drainage function and its effect on the yield, quality and plant–water relations of mustard over 2019–2021. Cut-soiler-simulated drains were made in a semi-controlled lysimeter (2 × 2 × 3; L*W*H m) as the main plot treatment in a double replicated split–split experiment with two soil types (subplot) and three irrigation water salinities (4, 8 and 12 dS m−1) as the sub-sub-plot treatment. The drainage volume of variable salinity (EC), dependent on the total water input, was substantially higher in the rainy season (April to October), i.e., 16.6, 7.76 and 12.0% during 2018, 2019 and 2020, with 1.7, 0.32 and 0.77 kg salt removal per lysimeter, compared to the post-rainy season. The mustard seed, straw and biological yields were improved by 31.4, 14.41 and 18.08%, respectively, due to a positive effect on plant–water relations. The mustard seeds produced in the cut-soiler-treated plots recorded higher oil, crude fiber and protein contents and a lower erucic acid content. The increase in salt load, by higher-salinity irrigation water, was also efficiently managed by using cut-soiler PSSD. It was found that the saline irrigation water up to 12.0 dS m−1 can be used under such PSSD without any extra salt loading. The present study showed the potential of cut-soiler PSSD in root zone salinity management by improving drainage in salt-affected arid regions.

Classifying freshwater salinity regimes in central and western U.S. streams and rivers

AbstractFreshwater salinization of rivers is occurring across the globe because of nonpoint source loading of salts from anthropogenic activities such as agriculture, urbanization, and resource extraction that accelerate weathering and release salts. Multidecadal trends in river salinity are well characterized, yet our understanding of annual regimes of salinity in rivers draining diverse central and western U.S. landscapes and their associated catchment attributes is limited. We classified annual salinity regimes in 242 stream locations through dynamic time warping and fuzzy c‐medoids clustering of salinity time series. We found two dominant regimes in salinity characterized by an annual summer–fall peak or spring decline. Using random forest regression, we found that precipitation amount, stream slope, and soil salinity were the most important predictors of salinity regime classification. Advancing our understanding of salinity regimes in rivers will improve our ability to predict and mitigate the effects of salinization in freshwater ecosystems through management interventions.

Impact of maternal intermittent fasting during pregnancy on cardiovascular, metabolic and renal function in adult rat offspring.

Pregnant Muslim women are exempt from fasting during Ramadan; however a majority are reported to fast. The impact of this form of maternal intermittent fasting (IF) on fetal development and offspring health is not well defined. Using a rat model, we have shown previously that maternal IF results in fetal growth restriction accompanied by changes in placental nutrient transport function. The aim of this study was to assess cardiovascular, metabolic and renal function in adult offspring of IF-exposed dams. Food was withheld from Wistar rats from 17:00 to 09:00 daily throughout pregnancy; controls had ad libitum access to food. Birth weight was unaffected; however male IF pups grew more slowly up to 10 weeks of age (P < 0.01) whereas IF females matched their control counterparts. Systolic blood pressure (SBP), glucose tolerance and basal renal function at 14 weeks were not affected by IF exposure. When offered saline solutions (0.9–2.1%) to drink, females showed a greater salt preference than males (P < 0.01); however there were no differences between dietary groups. A separate group of pups was weaned onto a 4% NaCl diet. SBP increased in IF pups sooner, at 7 weeks (P < 0.01), than controls which became hypertensive from 10 weeks. Renal function did not appear to differ; however markers of renal injury were elevated in IF males (P < 0.05). Maternal IF does not affect resting cardiovascular, metabolic and renal function; but when challenged by dietary salt load male IF offspring are more prone to renal injury.

Role of Oxidative Stress in Vascular Low-Grade Inflammation Initiation Due to Acute Salt Loading in Young Healthy Individuals.

This study aimed to investigate the effect of 7-day high-salt (HS) and the specific role of oxidative stress on vascular low-grade inflammation initiation in young salt-resistant healthy individuals. 30 young healthy individuals adhered to a 7-day low-salt (LS) diet (3.5 g salt/day), followed by a 7-day high-salt (HS) diet (~14.7 g salt/day) protocol. Pro- and anti-inflammatory cytokines, frequencies of peripheral blood Th17 and Treg cells, Th17/Treg ratio, enzymes SGK1, and p38/MAP kinase, as well as biomarkers of endothelial activation and oxidative stress, were measured before and after the 7-day HS diet protocol. Short-term HS diet significantly increased serum level of pro-inflammatory cytokines INF-γ, TNF-α, IL-9, and IL-17A levels, but also of anti-inflammatory cytokines IL-10 and TGF-β1. Relative amount of total SGK1 significantly increased, following the 7-day HS diet. Increased oxidative stress level, following HS diet, was negatively associated with the frequency of Treg cells. The increase in relative amount of total SGK1 in peripheral mononuclear cells following 7-day HS diet suggests lymphocyte (re)activation, in response to HS intake, resulting in enhanced production of pro-inflammatory (IL-17, INF-γ), but also anti-inflammatory cytokines (IL-10 and TGF-β1). Increased oxidative stress, due to HS loading, alters immune regulatory mechanisms, presumably via effects on Treg cells.

High dietary salt intake increases urinary NGAL excretion and creatinine clearance in healthy young adults.

In rodents and older patients with elevated blood pressure (BP), high dietary sodium increases excretion of biomarkers of kidney injury, but it is unclear whether this effect occurs in healthy young adults. The purpose of this study was to determine whether short-term high dietary salt increases urinary excretion of the kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in healthy young adults. Twenty participants participated in a double-blind, placebo-controlled, randomized crossover study. For 10 days each, participants were asked to consume salt (3,900 mg sodium) or placebo capsules. We measured BP during each visit, obtained 24-h urine samples for measurements of electrolytes, NGAL, and KIM-1, and assessed creatinine clearance. Compared with placebo, salt loading increased daily urinary sodium excretion (placebo: 130.3 ± 62.4 mmol/24 h vs. salt: 287.2 ± 72.0 mmol/24 h, P < 0.01). There was no difference in mean arterial BP (placebo: 77 ± 7 mmHg vs. salt: 77 ± 6 mmHg, P = 0.83) between conditions. However, salt loading increased the urinary NGAL excretion rate (placebo: 59.8 ± 44.4 ng/min vs. salt: 80.8 ± 49.5 ng/min, P < 0.01) and increased creatinine clearance (placebo: 110.5 ± 32.9 mL/min vs. salt: 145.0 ± 24.9 mL/min, P < 0.01). Urinary KIM-1 excretion was not different between conditions. In conclusion, in healthy young adults 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker NGAL but not KIM-1.NEW & NOTEWORTHY In healthy young adults, 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker neutrophil gelatinase-associated lipocalin despite no change in resting blood pressure.

Salt loading with unilateral nephrectomy accelerates decline in glomerular filtration rate in the hypertensive, obese, type 2 diabetic SDT fatty rat model of diabetic kidney disease.

For the evaluation of novel therapeutic agents for diabetic kidney disease (DKD), it is desirable to examine their efficacy in animal models by using the glomerular filtration rate (GFR) as an index. For this purpose, animal models that demonstrate a short-term GFR decline because of disease progression are required. Therefore, we aimed to develop such an animal model of DKD by using obese type 2 diabetic spontaneously diabetic Torii (SDT) fatty rats treated with salt loading by drinking water containing sodium chloride with or without unilateral nephrectomy. As a result, we have found that 0.3% salt loading with unilateral nephrectomy or 0.8% salt loading alone caused a rapid GFR decline, hypertension and rapid development of tubulointerstitial fibrosis. Moreover, the addition of losartan to a mixed diet suppressed the GFR decline in SDT fatty rats treated with 0.3% salt loading with unilateral nephrectomy. These results suggest that the model of SDT fatty rats treated with 0.3% salt loading and unilateral nephrectomy could be used as a hypertensive DKD model for evaluating therapeutic agents based on suppression of GFR decline.

Prevalence Rate of Proteinuria and Metabolic Acidosis Among Kidney Transplant Recipients in a Tertiary Teaching Hospital and Its Relationship to Dietary Intake

Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake. We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records. A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n=163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P=.008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis. The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

Sodium Accumulation and Blood Capillary Rarefaction in the Skin Predispose Spontaneously Hypertensive Rats to Salt Sensitive Hypertension.

Recent studies in humans and rats suggested that increased Na+ storage in the skin without parallel water retention may predispose to salt-sensitive hypertension. In the current studies, we compared tissue Na+ storage in salt sensitive spontaneously hypertensive rats (SHR) versus salt resistant normotensive Brown Norway (BN-Lx) rats. After salt loading (10 days drinking 1% NaCl solution), the SHR showed significant parallel increase in Na+-to-water as well as (Na++K+)-to-water ratios suggesting increased storage of osmotically inactive Na+ in the skin while no significant changes in skin electrolyte concentrations were observed in BN-Lx rats. SHR rats after salt treatment exhibited a nonsignificant decrease in skin blood capillary number (rarefaction) while BN-Lx rats showed significantly increased skin blood capillary density. Analysis of dermal gene expression profiles in BN-Lx rats after salt treatment showed significant up-regulation of genes involved in angiogenesis and proliferation of endothelial cells contrary to the SHR. Since the skin harbors most of the body’s resistance vessels it is possible that blood capillary rarefaction may lead to increased peripheral resistance and salt sensitivity in the SHR.

Salt-Induced Hepatic Inflammatory Memory Contributes to Cardiovascular Damage Through Epigenetic Modulation of SIRT3.

High salt intake is the leading dietary risk factor for cardiovascular diseases. Although clinical evidence suggests that high salt intake is associated with nonalcoholic fatty liver disease, which is an independent risk factor for cardiovascular diseases, it remains elusive whether salt-induced hepatic damage leads to the development of cardiovascular diseases. Mice were fed with normal or high-salt diet for 8 weeks to determine the effect of salt loading on liver histological changes and blood pressure, and salt withdrawal and metformin treatment were also conducted on some high-salt diet-fed mice. Adeno-associated virus 8, global knockout, or tissue-specific knockout mice were used to manipulate the expression of some target genes in vivo, including SIRT3 (sirtuin 3), NRF2 (NF-E2-related factor 2), and AMPK (AMP-activated protein kinase). Mice fed with a high-salt diet displayed obvious hepatic steatosis and inflammation, accompanied with hypertension and cardiac dysfunction. All these pathological changes persisted after salt withdrawal, displaying a memory phenomenon. Gene expression analysis and phenotypes of SIRT3 knockout mice revealed that reduced expression of SIRT3 was a chief culprit responsible for the persistent inflammation in the liver, and recovering SIRT3 expression in the liver effectively inhibits the sustained hepatic inflammation and cardiovascular damage. Mechanistical studies reveal that high salt increases acetylated histone 3 lysine 27 (H3K27ac) on SIRT3 promoter in hepatocytes, thus inhibiting the binding of NRF2, and results in the sustained inhibition of SIRT3 expression. Treatment with metformin activated AMPK, which inhibited salt-induced hepatic inflammatory memory and cardiovascular damage by lowering the H3K27ac level on SIRT3 promoter, and increased NRF2 binding ability to activate SIRT3 expression. This study demonstrates that SIRT3 inhibition caused by histone modification is the key factor for the persistent hepatic steatosis and inflammation that contributes to cardiovascular damage under high salt loading. Avoidance of excessive salt intake and active intervention of epigenetic modification may help to stave off the persistent inflammatory status that underlies high-salt-induced cardiovascular damage in clinical practice.

The Influence of Salt Sensitivity Phenotype on Sodium Excretion and Diuresis: A Chrononutrition Pilot Study.

Background Chrononutrition studies on interaction of diet/nutrients on endogenous circadian clocks and meal timing on metabolic homeostasis may be of importance in the management of nocturnal polyuria (NP), owing to loss of circadian rhythm in nighttime urination. Dietary salt restriction is an increasingly popular lifestyle recommendation for NP patients. Aim This study aims to evaluate the effect of an acute salt load on diuresis and to study the phenomenon of salt sensitivity. Methodology. Young, healthy men (n = 21, fasted and sober) ingested 500 ml of water on the control day and 8 g and 12 g of salt with water (500 ml) on two other days. Blood and urine samples were collected at 0 hrs, 2 hrs, and 4 hrs and voided volumes were recorded. Diuresis, serum and urine osmolality, sodium, potassium, urea, and creatinine were measured. Salt sensitivity was determined based on the rate of sodium excretion. Results Compared to 8 g, ingestion of 12 g of salt significantly increased diuresis after 4 hrs. Pure water load induced fast diuresis, whereas salt and water load initially reduced diuresis and promoted late increase in diuresis. The total voided volume was significantly lower in the salt sensitive individuals. Conclusion Taken together, salt sensitivity profile and type and time of fluid intake are important considerations to build effective personalized lifestyle recommendations for NP patients, which needs further investigation.

Critical Evaluation of the Potential of Organic Acids for the Environmentally Friendly Recycling of Spent Lithium-Ion Batteries

The need to recover valuable metals from spent lithium-ion batteries (LIBs) is undisputed. However, the environment and the climate are also affected by emissions from the recycling processes. Therefore, the call for environmentally friendly recycling methods is currently louder than ever. In the field of hydrometallurgical recovery of metals from spent LIBs, inorganic acids have so far proved to be an effective, but environmentally problematic, leaching agent, since the pollution of wastewater by high salt loads and the emission of toxic gases cannot be avoided. This has recently led to a trend towards the application of organic acids, as these have significantly more environmentally friendly properties. In order to continue this approach, and to improve it even further from an environmental point of view, this work focuses on the utilization of low leaching temperatures in combination with organic acids for the recovery of valuable metals from spent lithium-ion batteries. This can drastically reduce the required energy demand. Furthermore, attention is paid to higher (50–100 g·L−1) solid-liquid ratios, which are indispensable, especially with regard to the economic establishment of the tested process. The experimental verification of the feasibility using citric, oxalic, and formic acid showed the possibility of an efficient recovery of cobalt, nickel, and lithium. In particular, citric acid in combination with hydrogen peroxide as a reducing agent appears to be a suitable and environmentally friendly alternative to classical inorganic acids, even at low process temperatures, for the hydrometallurgical recycling of lithium-ion batteries.

Chloride accumulation in aboveground biomass of three macrophytes (Phragmites australis, Juncus maritimus, and Typha latifolia) depending on their growth stages and salinity exposure: application for Cl- removal and phytodesalinization.

Anthropogenic activities can be the source of saline solid wastes that need to be treated to reduce their salt load to meet the purposes of reuse, valorization or storage. In this context, chloride remediation can be achieved using high-salt accumulating plants. However, there is very limited information on the comparative potential of different species in the same environment, and only scarce data concerning their efficiency as a function of growth stage. In order to rationalize these selection criteria, three macrophytes i.e., common reed (Phragmites australis), sea rush (Juncus maritimus), and cattail (Typha latifolia), were cultivated at two growth stages (6-months old and 1-year old) for 65 days in Cl− spiked substrates (from 0 up to 24 ‰ NaCl). The plants’ survival and potential capacity for removal of Cl− from substrates and accumulation in shoots were investigated. For the three studied species, mature and juvenile plants display a high tolerance to salinity. However, mature specimens with higher shoot biomass and Cl− contents are capable of greater chloride removal than juvenile plants. The sole exception is P. australis which displays just the same phytoremediation potential for both mature and juvenile specimens. Moreover, P. australis has the lowest potential when compared with other species, being 1.5 and 3 times lower than for J. maritimus and T. latifolia. When considering the plant growth and the shoot biomass production, chloride removal rates from the substrate point that mature J. maritimus should preferentially be used to design an operational chloride remediation system. The results highlight the relevance of considering the growth stage of plants used for Cl− removal.Highlights1) Mature and juvenile specimens of J. maritimus, P. australis, and T. latifolia have high salinity tolerance in solid media spiked up to 24 ‰ NaCl.2) Mature plants have generally better Cl− removal and phytoremediation performances than juvenile specimens.3) J. maritimus is the most effective species for chloride phytoremediation with high survival and high Cl− sequestration in shoots.4) T. latifolia has high Cl− removal in shoots and good remediation capacities but also shows sign of stress.5) P. australis shows low Cl− sequestration and is a poor candidate for chloride remediation from substrate.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-021-17591-3.