A Personal and Practical Answer from A Clinical Perspective

Restoring sodium and fluid homeostasis in hemodialysis (HD) patients is a crucial aim to reduce cardiovascular burden and improve global outcome. This crucial target is achieved at maximum in one quarter of HD patients according to a recent study. Sodium and fluid balance relies on a multitarget approach involving dietary salt restriction, dialysis salt mass removal and eventually residual kidney function. Salt mass removal in hemodialysis relies on ultrafiltration (convective sodium), the dialysate–plasma sodium gradient (diffusive sodium) and total treatment time. Manual dialysate sodium prescription has three major aims: dialysate–plasma sodium gradient; sodium mass removal target; hemodialysis tolerance and patient risks. In the future, automated dialysate sodium adjustment by HD machine will facilitate this aim.

A sodium-translocating module linking succinate production to formation of a membrane potential in Prevotella bryantii

Ruminants such as cattle and sheep depend on the breakdown of carbohydrates from plant-based feedstuff which is accomplished by the microbial community in the rumen. Roughly 40% of the rumen microbiota belong to the family of Prevotellaceae which ferment sugars to organic acids such as acetate, propionate as well as succinate. These substrates are important nutrients for the ruminant. In a metaproteome analysis of the rumen of cattle, proteins that are homologous to the Na + -translocating NADH:quinone oxidoreductase (NQR) and the quinone:fumarate reductase (QFR) were identified in different Prevotella species. Here we show that fumarate reduction to succinate in anaerobically growing Prevotella bryantii is coupled to chemiosmotic energy conservation by a supercomplex composed of NQR and QFR. This S odium-translocating N ADH: F umarate oxido R eductase (SNFR) supercomplex was enriched by BN-PAGE and characterized by in-gel enzyme activity staining and mass spectrometry. High NADH oxidation (850 nmol min -1 mg -1 ), quinone reduction (490 nmol min -1 mg -1 ) and fumarate reduction (1200 nmol min -1 mg -1 ) activities, together with high expression levels, demonstrate that SNFR represents a charge-separating unit in P. bryantii . Absorption spectroscopy of SNFR exposed to different substrates revealed intramolecular electron transfer from the FAD cofactor in NQR to heme b cofactors in QFR. SNFR catalyzed the stoichiometric conversion of NADH and fumarate to NAD + and succinate. We propose that the regeneration of NAD + in P. bryantii is intimately linked to the build-up of an electrochemical gradient which powers ATP synthesis by electron transport phosphorylation. Importance Feeding strategies for ruminants are designed to optimize nutrient efficiency for animals and to prevent energy losses like enhanced methane production. Key to this are the fermentative reactions of the rumen microbiota, dominated by Prevotella sp. We show that succinate formation by P. bryantii is coupled to NADH oxidation and sodium-gradient formation by a newly described supercomplex consisting of Na + -translocating NADH:quinone oxidoreductase (NQR) and fumarate reductase (QFR), representing the S odium-translocating N ADH: F umarate oxido R eductase (SNFR) supercomplex. SNFR is the major charge-separating module, generating an electrochemical sodium gradient in P. bryantii . Our findings offer clues to the observation that use of fumarate as feed additive does not significantly increase succinate production, or decrease methanogenesis, by the microbial community in the rumen.

MO724IS INDIVIDUALIZED DIALYSATE SODIUM REASON FOR BETTER SURVIVAL IN HEMODIALYSIS PATIENTS?

Background and Aims We are uncertain about whether dialysate sodium improves overall health and well-being for people on haemodialysis, since there are a mixture of probably good and bad effects. Dialysate sodium is one of the most easy changeable parameter which can influence hemodynamic stability, echocardiography and laboratory parameters. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of dialysate sodium set up according to serum sodium. Method 77 nondiabetic subjects (41men; 36women) performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration setup at 138 mmol/L, followed by additional 24 month ssessions wherein dialysate sodium was set up according to pre-HD serum sodium concentration. Interdialytic weight gain (IDWG), echocardiography, laboratory parameters and survival were analysed. Results Sodium individualization resulted in significantly lower IDWG by using individualized sodium according to pre HD serum sodium compared to standard dialysate sodium (2.17±0.79 vs 1.93±0.64 kg, p<0,001). In all patients we confirmed positive sodium gradient and univariate regression analysis showed that by increasing the sodium gradient by 1 mmol/L, IDWG increased by an average of 0.189% and 7,1% changes in IDWG can be explain by changing of the sodium gradient. Echocardiography analysis showed an increase of 2.04 mm of left ventricular diastolic diameter (LVDD) by increasing the sodium gradient for 1mmol/L and significantly increased left ventricular mass (LVM) of 35.69 gr by 1kg increase of IDWG. Laboratory analysis showed statistical significant increase in Kt/V, URR (urea reduction rate), serum albumin and hemoglobin by using individualized dialysed sodium compared to standard dialysate sodium, respectively (1.50±0.24 vs 1.36±0.22; 70.80±5.24 vs 67.00±6.23%; 38.23±3.80 vs 34.46±2.53 g/L; 120.32±10.14 vs 114.62±10.34 g/L, p<0.001). We confirmed significant decrease in serum potassium, with no change in other electrolities (5.62±0.60vs 5.15±0.94). During the study, 7 patients died and binary logistic regression univariate analysis showed that significant predictors of mortality in patients dialyzed with individualized sodium dialysis according to pre-HD plasma sodium concentrations were Kt/V, URR, and CRP (C reactive protein). Analysis showed that patients with Kt/V lower than 1,2 have 8.8 times higher risk for death compared to patients with Kt/V>1,2, URR lower than 65% have 10,9 times higher risk compared to URR>65% and CRP higher than 10 mg/L have 10.2 times higher risk for death compared to patients with CRP lower than 10 mg/L Conclusion Individualization of dialysate sodium according to pre HD serum sodium concentration result in better IDWG control, improvement of fluid overload and regression of left ventricular hypertrophy, better dialysis adequacy and higher survival compared to standard dialysate sodium.

Prokaryotic Solute/Sodium Symporters: Versatile Functions and Mechanisms of a Transporter Family

The solute/sodium symporter family (SSS family; TC 2.A.21; SLC5) consists of integral membrane proteins that use an existing sodium gradient to drive the uphill transport of various solutes, such as sugars, amino acids, vitamins, or ions across the membrane. This large family has representatives in all three kingdoms of life. The human sodium/iodide symporter (NIS) and the sodium/glucose transporter (SGLT1) are involved in diseases such as iodide transport defect or glucose-galactose malabsorption. Moreover, the bacterial sodium/proline symporter PutP and the sodium/sialic acid symporter SiaT play important roles in bacteria–host interactions. This review focuses on the physiological significance and structural and functional features of prokaryotic members of the SSS family. Special emphasis will be given to the roles and properties of proteins containing an SSS family domain fused to domains typically found in bacterial sensor kinases.

Sodium (23Na) MRI of the Kidney: Basic Concept

The handling of sodium by the renal system is a key indicator of renal function. Alterations in the corticomedullary distribution of sodium are considered important indicators of pathology in renal diseases. The derangement of sodium handling can be noninvasively imaged using sodium magnetic resonance imaging (23Na MRI), with data analysis allowing for the assessment of the corticomedullary sodium gradient. Here we introduce sodium imaging, describe the existing methods, and give an overview of preclinical sodium imaging applications to illustrate the utility and applicability of this technique for measuring renal sodium handling.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Sodium (23Na) MRI of the Kidney: Experimental Protocol

Sodium handling is a key physiological hallmark of renal function. Alterations are generally considered a pathophysiologic event associated with kidney injury, with disturbances in the corticomedullary sodium gradient being indicative of a number of conditions. This experimental protocol review describes the individual steps needed to perform 23Na MRI; allowing accurate monitoring of the renal sodium distribution in a step-by-step experimental protocol for rodents.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Analysis Protocol for Renal Sodium (23Na) MR Imaging

The signal acquired in sodium (23Na) MR imaging is proportional to the concentration of sodium in a voxel, and it is possible to convert between the two using external calibration phantoms. Postprocessing, and subsequent analysis, of sodium renal images is a simple task that can be performed with readily available software. Here we describe the process of conversion between sodium signal and concentration, estimation of the corticomedullary sodium gradient and the procedure used for quadrupolar relaxation analysis.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

P1051WHICH MODEL OF DIALYSATE SODIUM PRESCRIPTION TO CHOOSE?

Background and Aims The dialysate sodium prescription remain unclear as an important component of sodium balance in HD patients Pre-hemodialysis (pre-HD) serum sodium levels can vary among different patients, therefore, a single dialysate sodium prescription may not be appropriate for all patients. Dialysate sodium is one of the most easy changeable parameter which can influence hemodynamic stability. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of prescription of different models of dialysate sodium Method 77 nondiabetic subjects (41 men; 36 women) performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration set up at 138 mmol/L, followed by additional 3 models of dialysate sodium (each model performed 2 months sessions with 2 months standard dialysate sodium between each model) wherein dialysate sodium was set up: model 1: according to pre-HD serum sodium concentration, model 2: according to sodium concentration in UF fluid, model 3: sodium profiling ( from 144 to 136 mmol/L). Blood pressure (BP), interdialytic weight gain (IDWG), thirst score, sodium gradient were analysed. After the standard dialysate sodium hemodialyses, the subjects were divided into 3 groups: normotensive (N=58), hypertensive (N= 14) and hypotensive (N=5) based on the average pre-HD systolic BP during the standard dialysate sodium hemodialyses. Results Model 1: resulted in significantly lower blood pressure (133,61±11.88 versus 153.60±14.26 mmHg; p=0.000) and IDWG (2.21±0.93 versus 1.87±0.92 kg; p=0.018) in hypertensive patients, whereas normotensive patients showed only significant decrease in IDWG (2.21±0.72 versus 2.06±0.65, p=0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p<0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. Thirst score was significantly lower in all patients with individualized-sodium HD and the use of antihypertensive drugs significantly reduced in hypertensive patients during the individualized phase. Model 2: resulted in significantly lower BP in normotensive and hypertensive patients (126.92±9.71 versus 124.08±8.71 mmHg; p=0.000; 153.60±14.26 versus 138.91±8.48 mmHg, accordingly), with no influence on IDWG, thirst score compared to standard dialysate sodium. Model 3: significantly higher BP and IDWG in all 3 groups (normotensive 126.92±9.71 versus 130.20±9.5 mmHg; p=0.001; IDWG 2.21±0.72 versus 2.34±0.82 kg, p=0,005; hypertensive 153.60±14.26 versus 157.58±5.0 mmHg; IDWG 2.21±0.93 versus 2.39±0.74 kg; p=0.005; hipotensive 79.81±11.78 versus 91.09±24.98 mmHg, IDWG 2.53±0.57 versus 2.73±0.15 kg, p=0.005) and significantly higher thirst score in normotensive and hypotensive patients, with no influence in hypertensive patients. Conclusion A reduction of the dialysate sodium concentration based on the pre HD serum sodium level of the patient, reduced the BP, IDWG, thirst score and use of antihypertensive drug compare to dialysate sodium according to sodium concentration in UF or sodium profiling. We recommend prescription of dialysate sodium according to pre HD serum sodium concentration.