Sodium set-point in haemodialysis: is it what we see clinically?

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Ruiz-Álvarez, Elena Corchete Prats, Tamar Talavan, Tamar Talaván, Roberto Alcázar Arroyo, Marta Puerta Carretero, Mayra Ortega Díaz, Mayra Ortega-Díaz" "autores" => array:18 [ 0 => array:2 [ "nombre" => "Marta" "apellidos" => "Albalate Ramón" ] 1 => array:2 [ "nombre" => "Marta" "apellidos" => "Albalate" ] 2 => array:2 [ "nombre" => "Patricia" "apellidos" => "de Sequera Ortiz" ] 3 => array:2 [ "nombre" => "Patricia" "apellidos" => "de Sequera" ] 4 => array:2 [ "nombre" => "Rafael" "apellidos" => "Pérez-García" ] 5 => array:2 [ "nombre" => "Rafael" "apellidos" => "Pérez-García" ] 6 => array:2 [ "nombre" => "Mª Jesús" "apellidos" => "Ruiz Alvarez" ] 7 => array:2 [ "nombre" => "María J." 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Ruiz-Álvarez, Elena Corchete Prats, Tamar Talavan, Tamar Talaván, Roberto Alcázar Arroyo, Marta Puerta Carretero, Mayra Ortega Díaz, Mayra Ortega-Díaz" "autores" => array:18 [ 0 => array:4 [ "nombre" => "Marta" "apellidos" => "Albalate Ramón" "email" => array:1 [ 0 => "malbalater@senefro.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 1 => array:4 [ "nombre" => "Marta" "apellidos" => "Albalate" "email" => array:1 [ 0 => "malbalater@senefro.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 2 => array:3 [ "nombre" => "Patricia" "apellidos" => "de Sequera Ortiz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 3 => array:3 [ "nombre" => "Patricia" "apellidos" => "de Sequera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 4 => array:3 [ "nombre" => "Rafael" "apellidos" => "Pérez-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 5 => array:3 [ "nombre" => "Rafael" "apellidos" => "Pérez-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 6 => array:3 [ "nombre" => "Mª Jesús" "apellidos" => "Ruiz Alvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "affc" ] ] ] 7 => array:3 [ "nombre" => "María J." "apellidos" => "Ruiz-Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "affd" ] ] ] 8 => array:3 [ "nombre" => "Elena" "apellidos" => "Corchete Prats" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "affe" ] ] ] 9 => array:3 [ "nombre" => "Elena" "apellidos" => "Corchete" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 10 => array:3 [ "nombre" => "Tamar" "apellidos" => "Talavan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "afff" ] ] ] 11 => array:3 [ "nombre" => "Tamar" "apellidos" => "Talaván" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "affd" ] ] ] 12 => array:3 [ "nombre" => "Roberto" "apellidos" => "Alcázar Arroyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 13 => array:3 [ "nombre" => "Roberto" "apellidos" => "Alcázar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 14 => array:3 [ "nombre" => "Marta" "apellidos" => "Puerta Carretero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 15 => array:3 [ "nombre" => "Marta" "apellidos" => "Puerta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] 16 => array:3 [ "nombre" => "Mayra" "apellidos" => "Ortega Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "affa" ] ] ] 17 => array:3 [ "nombre" => "Mayra" "apellidos" => "Ortega-Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Infanta Elena, Madrid, Madrid, Spain, " "etiqueta" => "a" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Infanta Elena, Madrid, " "etiqueta" => "b" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Laboratorio de Bioquimica, Hospital Infanta Elena, Madrid, Madrid, Spain, " "etiqueta" => "c" "identificador" => "affc" ] 3 => array:3 [ "entidad" => "Laboratorio de Bioquímica, Hospital Universitario Infanta Elena, Madrid, " "etiqueta" => "d" "identificador" => "affd" ] 4 => array:3 [ "entidad" => "Servicio de Nefrologia, Hospital Infanta Elena, Madrid, Madrid, Spain, " "etiqueta" => "e" "identificador" => "affe" ] 5 => array:3 [ "entidad" => "Laboratorio de Bioquímica, Hospital Infanta Elena, Madrid, Madrid, Spain, " "etiqueta" => "f" "identificador" => "afff" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Set-point de sodio en hemodiálisis: ¿es lo que vemos en la clínica?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52154_en_t18.12217.jpg" "Alto" => 1031 "Ancho" => 1041 "Tamanyo" => 213272 ] ] "descripcion" => array:1 [ "en" => "Factors involved in water and salt intake" ] ] ] "textoCompleto" => "In the last two years we have read several studies that establish a link between hyponatraemia and mortality in haemodialysis (HD) patients.1-4 In another study, Sahin et al.5 reported that hyponatraemia was only a predictor of mortality in diabetic HD patients. It is important to highlight that in each of these studies the plasma sodium value chosen as the predictive value was different: Natraemia at the time of inclusion (single value) or mean natraemia (over 3 months or one year). This decision is justified on the basis of publications that state that each patient has fixed natraemia or what has come to be known as setpoint.6-10Natraemia indicates the relationship between the quantity of sodium and water in plasma. In HD patients, the determining factors of these elements are: 1) intake and 2) removal via HD and via the kidneys if there is residual renal function (RRF). Intake is regulated by physiological and non-physiological factors (Table 1);11 losing the renal capacity to remove water and salt makes the water/salt intake relationship a determining factor of natraemia. In fact, the study by Maduell et al. that measured plasma conductivity demonstrated that a low salt diet decreases pre-dialysis plasma conductivity.12 If we consider HD in terms of the balance achieved, we may generate mechanisms that stimulate or inhibit intake.13 For example, a positive sodium balance will increase thirst, blood pressure (BP) and extracellular volume (ECV).14-16 By contrast, if dialysate conductivity decreases progressively, as demonstrated by Manlucu et al., sodium removal will increase and BP and interdialysis weight gain (IDG) will decrease, which will modify plasma conductivity.17 Thomson et al.18 also demonstrated how changes in the HD regimen may alter natraemia. With the foregoing in mind for clinical practice, due to multiple determining factors, natraemia may vary both in accordance with intake and variations in the HD regimen, and as such, it is necessary to distinguish between them, particularly if we wish to correct hyponatraemia.Moreover, natraemia governs volume distribution in different body spaces (intracellular volume [ICV]/ECV).19 Hypervolaemia, which has been associated with mortality,20 depends on an increased amount of sodium, not natraemia. But measuring the state of hydration is complicated and it has led to bioimpedance becoming widespread in clinical practice. However, we are unaware of any study that has related natraemia to hydration or the distribution of body volumes.With these premises and in order to improve our clinical practice, we considered: 1) the variability of natraemia over time in each patient in relation to the measuring method; 2) the relationship between natraemia and different clinical and HD parameters, and 3) the relationship between natraemia and the distribution of body volume measured by bioimpedance. MATERIAL AND METHOD This is a retrospective, observational, clinical study of natraemia in 98 patients, with the only inclusion criteria being time on chronic HD of more than 3 months in the Hospital Universitario Infanta Leonor de Madrid between January 2010 and October 2012. Follow-up ranged from 4 months to the entire collection period, with a mean follow-up of 23.2 (10) months.We collected data using the normal software (TSS®, Fresenius) on:<ul><li>Patients’ demographic and clinical characteristics: sex, age, time on HD, RRF measured as mean urea/creatinine clearance (>3ml/min), diabetes mellitus (yes/no), heart disease (ejection fraction <40%), cirrhosis with episodes of fluid retention (yes/no) and treatment with diuretics or antidepressants.</li><li>HD sessions: technique, duration and total conductivity in dialysate. We also measured the annual mean (years 2010, 2011 and 2012) dry weight, pre-dialysis systolic and diastolic BP and IDG. We calculated IDG as a percentage of dry weight (IDG%).</li><li>In our unit, we individually managed total dialysate conductivity. This was carried out in accordance with: BP, IDG and tolerance to the session (cramp, low blood pressure). Initial conductivity was 14mS/cm. If BP values were higher than 150/90mmHg, IDG higher than 1l/24h and haemodynamic tolerance during the session was good, we gradually reduced it by 0.1 to a minimum of 13.6Ms/cm. However, in patients with cramp and low BP, we increased conductivity by 0.1 up to a maximum of 14.2mS/cm.</li><li>Pre-dialysis tests carried out routinely: date and time of removal of glucose and sodium. </li><li>Bioimpedance measurements (carried out with a Body Compositor Monitor [BCM]®, Fresenius) performed before dialysis on the middle day of the week, in accordance with the normal protocol. We only used the measurements carried out in the same week as the natraemia biochemical test and we measured: pre-dialysis weight, overhydration (OH), ECV and ICV. We calculated relative overhydration (OH/ECV X 100)%, ECV/ICV, ECV percentage (ECV X 100/pre-dialysis weight) and ICV percentage (ICV x 100/pre-dialysis weight).</li></ul> Laboratory tests and calculations of study parameters The normal biochemical tests were carried out with an indirect potentiometry autoanalyser (ADVIA® 2400 Clinical Chemistry System, Siemens). The coefficient of variation (CV) was 0.7 for Na of 121mEq/l and 0.8 for Na of 142mEq/l.In a group of 59 patients, we measured natraemia using two methods: the aforementioned indirect potentiometry method and direct potentiometry from the same serum sample (Rapidlab 1265®, Siemens).All natraemias were corrected for glucose, considering that sodium decreases 1.6mEq/l for each 100mg/dl increase in glucose above 200mg/dl. Statistical analysis The data in this study were presented as mean and standard deviation (SD) or median (range) in non-normal distribution values. We calculated the CV of natraemia from the mean and SD of each patient.For comparison of the two continuous independent variables we used the Student’s t-test for non-paired samples. To compare discrete variables we used the Χ2 test and Fisher’s test when necessary (n<5). We calculated Pearson’s correlation coefficient to assess the association between quantitative variables. A P value <.05 was considered to be statistically significant.We created two study groups in accordance with natraemia: one based on the clinical definition of hyponatraemia22 (<135mEq/l) and another based on our statistical findings by tertiles.We used the SPSS version 15.0 (SPSS, Chicago, USA) to carry out statistical analysis and create the graphs.                                                                                       RESULTS We studied 63 males and 35 females, with a median age of 69.6 (21-91) years. The median replacement therapy time was 33 (3-322) months. Thirty-six had RRF. Forty-three were diabetic, 27 had heart disease and 6 had liver disease. We collected data from patients’ clinical records with regard to treatment with drugs that potentially induce hyponatraemia, such as diuretics (n=12) and antidepressants (n=11).In the follow-up 13 patients had died, 11 had received a transplant and 11 had been transferred to another centre or had changed technique. Overall natraemia tests In the recall period we carried out a total of 1802 sodium tests. The mean value was 138 (3.2) mEq/l, with a range between 122 and 147mEq/l (mean range 10.5 [4.3] mEq/l). Mean natraemia corrected for glucose was 139.1 (3.6) mEq/l. The difference between the two natraemias was statistically significant, P<.0001. Of the total tests carried out, 215 (11.9%) were less than 135mEq/l, while 811 (45%) were greater than 140mEq/l. Their distribution is displayed in Figure 1.To measure variability, we first analysed the mean number of natraemias obtained for each patient, which was 18.7 (4-34). The mean CV of each patient (for corrected natraemia) was 2% (0.8) (range: 1%-5.6%). There was a negative correlation between natraemia and CV: r=-0.63, P<.0001. As such, when we carried out a separation based on natraemia tertiles (Table 2), it was highlighted that lower natraemias had a significantly higher CV, SD and range.Lastly, Table 3 displays the number of natraemias below 135 and above 140 recorded per patient. Relationship between natraemias and clinical parameters Diabetics had a lower (corrected) natraemia than non-diabetics, 138 (2.4) compared with 139 (2) mEq/l, P<.003, with CV of 2.3 (0.9) compared with 1.9% (0.7) (P<.01) and SD of 3.2 (1.2) compared with 2.5 (0.9) mEq/l (P<.04). There were no significant differences in range between the two groups. IDG was not statistically different.We did not observe differences in natraemias according to sex, age, time on dialysis, heart disease, liver disease, medication use or RRF (Table 4). Natraemia was not lower in those who had died during follow-up. Relationship between natraemia and dialysis parameters We found a positive relationship between mean natraemia in each patient and total dialysate conductivity, while the correlation between natraemia and IDG % was negative. There was no correlation between natraemia and pre-dialysis systolic and diastolic BP (Table 5). There were no differences in accordance with the dialysis technique used. Comparison between direct and indirect potentiometry In a prospective control that included 59 patients, we tested natraemia from the same extraction of pre-dialysis blood in both methods.Pearson’s correlation coefficient between the two methods was 0.89 (95% confidence interval: 0.83-0.93) (Figure 2). Bland-Altman’s test showed that there were no significant differences; we were able to confirm that at least 3% of the data exceeded the two SD. We found no statistical correlation between natraemia and glucose, cholesterol or total protein concentration. Proteins ranged from 5.7 to 7.2mg/dl. Relationship between natraemia and body volumes We tested 136 BCM measurements in 57 patients on whom we had carried out bioimpedance and extracted the samples in the same week.The mean values obtained were: natraemia 139.5 (3.1) mEq/l, OH: 1l (-2.8-8.1), OH/ECV %: 6.8 (–16.7-34.2), ECV 16l (3.4), ECV %/weight 22% (3), ICV 16.3l (4.1), ICV %/weight 22.4% (4.7), ECV/ICV: 1 (0.1). 16.2% of measurements displayed OH/ECV % values above 15%. We did not find any correlation between any of these parameters and natraemia at the time they were measured or when we separated them in accordance with this group’s natraemia tertiles (Table 6). DISCUSSION Our study has three main results. The first is that natraemia is not constant in all patients. The second is that natraemia is positively related with dialysate conductivity and negatively with IDG %. The third result is that natraemia is not related to the distribution of body water, which highlights the importance of separating the concepts of natraemia and volaemia.Until present, three studies have stated that there is a sodium set-point or “fixed” natraemia in HD patients based on a low CV. Our data confirm that natraemia has a CV that may be considered low mathematically but clinical practice (Table 3) and the wide range reveal that the sodium/water relationship may change and may not be constant due to multiple factors. This table clearly demonstrates the situation that we find daily in clinical practice, since almost 60% of patients had some sodium measurement that was less than 135 or more than 140mEq/l. By the same token, Basile et al.8 found that despite a low CV, the intraindividual range was 6.2±2.9 and was higher than 10mEq/l in 11 subjects. In addition, Peixoto et al.6 despite claiming that this set-point exists, demonstrated that 21% of patients had a range higher than 10mEq/l. Furthermore, our results show that variability is higher in patients with natraemia of less than 138mEq/l (Table 2). It is easy to observe from the physiological point of view that although thirst is very well regulated, in daily life there are other non-physiological factors that modify liquid or salt intake and that make natraemia inconstant. Strikingly, CV is higher in diabetics, which could be attributed to the fact that in this group, thirst is stimulated in accordance with blood glucose, although IDG is not statistically significant. Although in previous studies the percentage of diabetics was high (reaching 47% in some studies6), until now, this population had not been studied separately and furthermore it has a lower (corrected) natraemia per se. This variability is important when evaluating natraemia as a mortality factor considered “constant” and determining its significance and the value to be selected for these studies and investigating whether there are differences in accordance with the studied populations.Out of the three studies cited regarding the set-point, in two of them natraemia was measured with indirect potenciometry7,9 and in the other with direct potentiometry.8 In normal clinical practice the method used is indirect potentiometry, considered the reference for evaluating other methods.23 Our results show an excellent correlation between the two methods and all the results were obtained in the same laboratory, which complies with ISO standards. In any case, given that the method employed in most hospitals is indirect potentiometry, we believe that our results are the most relevant and most applicable to clinical practice.In our study we did not find differences in natraemia in terms of the associated diseases or mortality, which may be due to the fact that we had a small number of patients in comparison to the other large studies previously published and because we used a mean natraemia over a long follow-up period. Only diabetic patients had lower corrected natraemias, which we attribute to the abovementioned causes.In relation to the dialysis parameters, we found an association between natraemia and total conductivity in the dialysate, which had not been found in other studies. These results must be interpreted while bearing in mind that it is a retrospective study of a unit in which we individualised dialysate conductivity on the basis of its potential effect on BP and IDG, as was explained in the section “Material and Method”. For example, on the basis of the criteria of the year 2012: 6% of patients had a conductivity of 13.6%, 18.7% had 13.7, 31.8% had 13.8, 24.8% had 13.9, 16.9% had 14 and 1.5% had 14.1mS/sec conductivity. In the major studies cited,3,4 when they tried to explain the role that sodium selection in dialysate plays in mortality, we found disparate results that were difficult to interpret. They did find that sodium concentration in dialysate is related to IDG and BP, but not to natraemia. However, in these studies, the criteria for choosing the dialysate are unknown. The effects of changing sodium concentration in dialysate on natraemia found in the literature are variable. While this relationship is clear in the study by Manculu et al.17, in which decreasing dialysate conductivity decreases initial plasma conductivity, the results are different in the study by Paula et al.24. If the differences are due to the latter being based on sodium that is calculated by machine, this is not explained. Many current monitors calculate sodium plasma concentration on the basis of ionic dialysance. Although plasma natraemia and calculated natraemia are different,25 their values are very useful in clinical practice. The point is that when we act on dialysate conductivity to intervene in BP and IDG we modify the sodium balance by diffusion and as a result, we influence natraemia. We do not know the consequences of this action. Since our study is retrospective, we cannot know if lower natraemia is the cause or the consequence of choosing a dialysate with lower conductivity in accordance with clinical parameters. On viewing the existing literature and our data, when the dialysis regimen is modified (changes in conductivity17 or frequency18) natraemia may vary. As such, if decreasing sodium conductivity to control BP or IDG has the result of decreasing natraemia, it would be necessary to conduct new prospective studies to determine if the intended benefit might be offset by decreased natraemia.Natraemia was also negatively related to IDG %. This could be explained by these patients having more sodium gain than water, highlighting the water/sodium relationship, or else because in those who had higher gains we tried to decrease sodium concentration in dialysate to limit the positive balance and thirst. As with the previous point, since this was a retrospective study we were unable to distinguish between cause and effect.Lastly, we would like to comment on the bioimpedance results. Contrary to what we theoretically thought we would find, patients with hyponatraemia did not display a relative increase in ICV or differences in distribution between ECV and ICV or OH. This finding highlights that, like with the population with normal renal function, we could find hyponatraemia with hyper/hypo/normovolaemia and this highlights the complexity of managing the balances volaemia (=sodium) and natraemia (=water) with HD. Until now, no publication had been written in this regard, which means that our study is contributing very new information and is opening a field of research.As limitations to our results, we have already mentioned that the retrospective nature is a confusing factor when it comes to interpreting the relationship between natraemia and dialysate conductivity and IDG % but it does not affect the variability results for natraemia in a normal clinical practice in which the situation can change. The small number of patients could explain why we did not find a difference in mortality or other epidemiological factors. Lastly, must say that we know bioimpedance is not a direct measure of different volumes but it is a very useful tool and one that is employed extensively in dialysis units to assess hydration. As such, although it is not the gold standard method for measuring body water, its use has been validated and on the basis of daily practice, we can say that its results on the absence of a relationship between hydration and natraemia are clear.In conclusion, natraemia in HD patients has a low CV, but it does not display a constant value, especially in patients with a tendency for hyponatraemia and it is necessary to correct it for blood glucose. This CV is higher in diabetics, in whom natraemia is lower. The lack of association between natraemia and volume highlights the need to independently assess the sodium and salt balances that each patient requires, insisting once again on the importance of individualised HD.  Conflicts of interest The authors declare that they have no conflicts of interest related to the contents of this article.<a href="grande/12117_16025_52154_en_t18.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52154_en_t18.12217.jpg" alt="Factors involved in water and salt intake"></img></a>Table 1. Factors involved in water and salt intake<a href="grande/12117_16025_52155_en_t28.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52155_en_t28.12217.jpg" alt="Differences in the intraindividual coefficient of variation and standard deviation in accordance with natraemia tertiles"></img></a>Table 2. Differences in the intraindividual coefficient of variation and standard deviation in accordance with natraemia tertiles<a href="grande/12117_16025_52156_en_t38.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52156_en_t38.12217.jpg" alt="Distribution of patients in accordance with the natraemias found"></img></a>Table 3. Distribution of patients in accordance with the natraemias found<a href="grande/12117_16025_52157_en_t48.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52157_en_t48.12217.jpg" alt="Percentage of patients grouped by tertiles according to clinical characteristics"></img></a>Table 4. Percentage of patients grouped by tertiles according to clinical characteristics<a href="grande/12117_16025_52158_en_t58.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52158_en_t58.12217.jpg" alt="Mean natraemia correlation for each patient with conductivity used in the dialysate over one year and weight gain during this year"></img></a>Table 5. Mean natraemia correlation for each patient with conductivity used in the dialysate over one year and weight gain during this year<a href="grande/12117_16025_52159_en_t68.12117.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52159_en_t68.12117.jpg" alt="Bioimpedance results in accordance with the natraemia tertiles "></img></a>Table 6. Bioimpedance results in accordance with the natraemia tertiles <a href="grande/12117_16025_52160_en_f18.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52160_en_f18.12217.jpg" alt="Distribution of all natraemias measured (n=1802)."></img></a>Figure 1. Distribution of all natraemias measured (n=1802).<a href="grande/12117_16025_52161_en_f28.12217.jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52161_en_f28.12217.jpg" alt="Relationship between direct and indirect potentiometry"></img></a>Figure 2. Relationship between direct and indirect potentiometry" "pdfFichero" => "P1-E562-S4392-A12117-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439511" "palabras" => array:1 [ 0 => "Composición corporal" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439513" "palabras" => array:1 [ 0 => "Bioimpedancia" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439515" "palabras" => array:1 [ 0 => "Hemodiálisis" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec439517" "palabras" => array:1 [ 0 => "Natremia" ] ] ] "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439512" "palabras" => array:1 [ 0 => "Body composition" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439514" "palabras" => array:1 [ 0 => "Bioimpedance" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439516" "palabras" => array:1 [ 0 => "Haemodialysis" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec439518" "palabras" => array:1 [ 0 => "Natraemia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "Introducción: La natremia en los pacientes en hemodiálisis (HD) se considera constante, contrariamente a lo observado en la clínica diaria. Su relación con parámetros clínicos, de diálisis y con la distribución del agua corporal (AC) no está aclarada. Objetivos: Estudiar: 1) la variabilidad intrasujeto de la natremia, 2) la relación entre natremia y parámetros clínicos y dialíticos y 3) la relación entre natremia y distribución del AC por bioimpedancia. Material y métodos: Estudio observacional retrospectivo de 98 pacientes en HD crónica. Se recogieron características clínicas, de HD, natremia, glucemia y medidas de bioimpedancia. Resultados: Sesenta y tres varones y 35 mujeres de 69,6 (21-91) años con seguimiento de 23,2 (10) meses. Variabilidad: 1802 determinaciones de sodio: natremia media 138 (3,2) y corregida para glucemia: 139,1 (3,6) mEq/l, p < 0,0001. El coeficiente de variación (CV) intrasujeto fue 2 (0,8) % (rango: 1-5,6 %) y correlacionó negativamente con la natremia (r = –0,63, p < 0,0001). Parámetros clínicos: en diabéticos la natremia corregida era inferior a en no-diabéticos 138 (2,4) frente a 139 (2) mEq/l, p < 0,003, con CV de 2,3 (0,9) frente a 1,9 (0,7) % (p < 0,01) y desviación estándar de 3,2 (1,2) frente a 2,5 (0,9) mEq/l (p < 0,04). No encontramos diferencias según sexo, edad, tiempo en diálisis, cardiopatía, hepatopatía, fármacos, función renal residual ni mortalidad. Parámetros de HD: relación positiva entre natremia y conductividad del líquido de diálisis y negativa con ganancia de peso interdiálisis (GID). Bioimpedancia: no relación entre distribución AC y natremia. Conclusiones: La natremia varía en cada paciente y se relaciona positivamente con la conductividad y negativamente con la GID. En diabéticos la natremia es más baja y el CV es mayor. No existe relación entre natremia y la distribución del AC." ] "en" => array:1 [ "resumen" => "Background: Natraemia in haemodialysis (HD) patients is considered constant contrary to daily clinical observations. Its relationship with clinical parameters, dialysis parameters and body water (BW) distribution is not clear. Objectives: The aims of this study were to know 1) the intraindividual variability of natraemia, 2) the relationship between natraemia and clinical and dialysis parameters and 3) the relationship between natraemia and BW distribution by bioimpedance. Material and Method: Observational retrospective study on 98 chronic HD patients. Clinical, HD and natraemia, glucose and bioimpedance data were collected. Results: We included 63 males and 35 females of 69.6 (21-91) years of age, with a follow-up of 23.2 (10) months. Variability: 1802 sodium measurements: mean natraemia 138 (3.2) mEq/l and corrected for glucose: 139.1 (3.6) mEq/l, p<.0001. Intraindividual coefficient of variation (CV) was 2% (0.8) (range 1-5.6%) and it correlated negatively with natraemia (r=-0.63, p<.0001). Clinical parameters: corrected natraemia was lower in diabetics than in non-diabetics 138 (2.4) compared with 139 (2) mEq/l, p<.003, CV 2.3 (0.9) compared with 1.9 (0.7)% (p<.01) and SD 3.2 (1.2) compared with 2.5 (0.9) mEq/l (p<.04). No differences according to gender, age, HD time, cardiac or liver disease, medication use, residual renal function or mortality were found. HD parameters: a positive relationship was found between natraemia and total dialysate conductivity and it was negative with interdialysis weight gain (IDG). - Bioimpedance: no relationship was found between natraemia and BW distribution. Conclusions: Natraemia varies in each patient and is related positively with conductivity and negatively with IDG. In diabetics natraemia is lower and CV is higher. There is no relationship between natraemia and BW distribution." ] ] "multimedia" => array:8 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52154_en_t18.12217.jpg" "Alto" => 1031 "Ancho" => 1041 "Tamanyo" => 213272 ] ] "descripcion" => array:1 [ "en" => "Factors involved in water and salt intake" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Tab. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52155_en_t28.12217.jpg" "Alto" => 308 "Ancho" => 2186 "Tamanyo" => 133450 ] ] "descripcion" => array:1 [ "en" => "Differences in the intraindividual coefficient of variation and standard deviation in accordance with natraemia tertiles" ] ] 2 => array:8 [ "identificador" => "fig3" "etiqueta" => "Tab. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52156_en_t38.12217.jpg" "Alto" => 294 "Ancho" => 2161 "Tamanyo" => 156587 ] ] "descripcion" => array:1 [ "en" => "Distribution of patients in accordance with the natraemias found" ] ] 3 => array:8 [ "identificador" => "fig4" "etiqueta" => "Tab. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52157_en_t48.12217.jpg" "Alto" => 624 "Ancho" => 2164 "Tamanyo" => 289274 ] ] "descripcion" => array:1 [ "en" => "Percentage of patients grouped by tertiles according to clinical characteristics" ] ] 4 => array:8 [ "identificador" => "fig5" "etiqueta" => "Tab. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52158_en_t58.12217.jpg" "Alto" => 193 "Ancho" => 2171 "Tamanyo" => 105194 ] ] "descripcion" => array:1 [ "en" => "Mean natraemia correlation for each patient with conductivity used in the dialysate over one year and weight gain during this year" ] ] 5 => array:8 [ "identificador" => "fig6" "etiqueta" => "Tab. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52159_en_t68.12117.jpg" "Alto" => 377 "Ancho" => 2177 "Tamanyo" => 148884 ] ] "descripcion" => array:1 [ "en" => "Bioimpedance results in accordance with the natraemia tertiles" ] ] 6 => array:8 [ "identificador" => "fig7" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52160_en_f18.12217.jpg" "Alto" => 946 "Ancho" => 1019 "Tamanyo" => 117465 ] ] "descripcion" => array:1 [ "en" => "Distribution of all natraemias measured (n=1802)." ] ] 7 => array:8 [ "identificador" => "fig8" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "12117_16025_52161_en_f28.12217.jpg" "Alto" => 758 "Ancho" => 2108 "Tamanyo" => 200447 ] ] "descripcion" => array:1 [ "en" => "Relationship between direct and indirect potentiometry" ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Waikar SS, Curhan GC, Brunelli SM. 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Set-point de sodio en hemodiálisis: ¿es lo que vemos en la clínica?

Marta Albalate Ramóna, Marta Albalateb, Patricia de Sequera Ortiza, Patricia de Sequerab, Rafael Pérez-Garcíaa, Rafael Pérez-Garcíab, Mª Jesús Ruiz Alvarezc, María J. Ruiz-Álvarezd, Elena Corchete Pratse, Elena Corcheteb, Tamar Talavanf, Tamar Talavánd, Roberto Alcázar Arroyoa, Roberto Alcázarb, Marta Puerta Carreteroa, Marta Puertab, Mayra Ortega Díaza, Mayra Ortega-Díazb

a Servicio de Nefrología, Hospital Infanta Elena, Madrid, Madrid, Spain,

b Servicio de Nefrología, Hospital Universitario Infanta Elena, Madrid,

c Laboratorio de Bioquimica, Hospital Infanta Elena, Madrid, Madrid, Spain,

d Laboratorio de Bioquímica, Hospital Universitario Infanta Elena, Madrid,

e Servicio de Nefrologia, Hospital Infanta Elena, Madrid, Madrid, Spain,

f Laboratorio de Bioquímica, Hospital Infanta Elena, Madrid, Madrid, Spain,

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as demonstrated by Manlucu et al&#46;&#44; sodium removal will increase and BP and interdialysis weight gain &#40;IDG&#41; will decrease&#44; which will modify plasma conductivity&#46;<span class="elsevierStyleSup">17 </span>Thomson et al&#46;<span class="elsevierStyleSup">18</span> also demonstrated how changes in the HD regimen may alter natraemia&#46; With the foregoing in mind for clinical practice&#44; due to multiple determining factors&#44; natraemia may vary both in accordance with intake and variations in the HD regimen&#44; and as such&#44; it is necessary to distinguish between them&#44; particularly if we wish to correct hyponatraemia&#46;</p><p class="elsevierStylePara">Moreover&#44; natraemia governs volume distribution in different body spaces &#40;intracellular volume &#91;ICV&#93;&#47;ECV&#41;&#46;<span class="elsevierStyleSup">19</span> Hypervolaemia&#44; which has been associated with mortality&#44;<span class="elsevierStyleSup">20 </span>depends on an increased amount of sodium&#44; not natraemia&#46; But measuring the state of hydration is complicated and it has led to bioimpedance becoming widespread in clinical practice&#46; However&#44; we are unaware of any study that has related natraemia to hydration or the distribution of body volumes&#46;</p><p class="elsevierStylePara">With these premises and in order to improve our clinical practice&#44; we considered&#58; 1&#41; the variability of natraemia over time in each patient in relation to the measuring method&#59; 2&#41; the relationship between natraemia and different clinical and HD parameters&#44; and 3&#41; the relationship between natraemia and the distribution of body volume measured by bioimpedance&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">This is a retrospective&#44; observational&#44; clinical study of natraemia in 98 patients&#44; with the only inclusion criteria being time on chronic HD of more than 3 months in the Hospital Universitario Infanta Leonor de Madrid between January 2010 and October 2012&#46; 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Fresenius&#41; performed before dialysis on the middle day of the week&#44; in accordance with the normal protocol&#46; We only used the measurements carried out in the same week as the natraemia biochemical test and we measured&#58; pre-dialysis weight&#44; overhydration &#40;OH&#41;&#44; ECV and ICV&#46; We calculated relative overhydration &#40;OH&#47;ECV X 100&#41;&#37;&#44; ECV&#47;ICV&#44; ECV percentage &#40;ECV X 100&#47;pre-dialysis weight&#41; and ICV percentage &#40;ICV x 100&#47;pre-dialysis weight&#41;&#46;</li></ul><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Laboratory tests and calculations of study parameters</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The normal biochemical tests were carried out with an indirect potentiometry autoanalyser &#40;ADVIA<span class="elsevierStyleSup">&#174;</span>&#160;2400 Clinical Chemistry System&#44; Siemens&#41;&#46; The coefficient of variation &#40;CV&#41; was 0&#46;7 for Na of 121mEq&#47;l and 0&#46;8 for Na of 142mEq&#47;l&#46;</p><p class="elsevierStylePara">In a group of 59 patients&#44; we measured natraemia using two methods&#58; the aforementioned indirect potentiometry method and direct potentiometry from the same serum sample &#40;Rapidlab 1265<span class="elsevierStyleSup">&#174;</span>&#44; Siemens&#41;&#46;</p><p class="elsevierStylePara">All natraemias were corrected for glucose&#44; considering that sodium decreases 1&#46;6mEq&#47;l for each 100mg&#47;dl increase in glucose above 200mg&#47;dl&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The data in this study were presented as mean and standard deviation &#40;SD&#41; or median &#40;range&#41; in non-normal distribution values&#46; We calculated the CV of natraemia from the mean and SD of each patient&#46;</p><p class="elsevierStylePara">For comparison of the two continuous independent variables we used the Student&#8217;s t-test for non-paired samples&#46; To compare discrete variables we used the &#935;<span class="elsevierStyleSup">2 </span>test and Fisher&#8217;s<span class="elsevierStyleSup"> </span>test when necessary &#40;n&#60;5&#41;&#46; We calculated Pearson&#8217;s correlation coefficient to assess the association between quantitative variables&#46; A <span class="elsevierStyleItalic">P</span> value &#60;&#46;05 was considered to be statistically significant&#46;</p><p class="elsevierStylePara">We created two study groups in accordance with natraemia&#58; one based on the clinical definition of hyponatraemia<span class="elsevierStyleSup">22</span> &#40;&#60;135mEq&#47;l&#41; and another based on our statistical findings by tertiles&#46;</p><p class="elsevierStylePara">We used the SPSS version 15&#46;0 &#40;SPSS&#44; Chicago&#44; USA&#41; to carry out statistical analysis and create the graphs&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160; </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We studied 63 males and 35 females&#44; with a median age of 69&#46;6 &#40;21-91&#41; years&#46; The median replacement therapy time was 33 &#40;3-322&#41; months&#46; Thirty-six had RRF&#46; Forty-three were diabetic&#44; 27 had heart disease and 6 had liver disease&#46; We collected data from patients&#8217; clinical records with regard to treatment with drugs that potentially induce hyponatraemia&#44; such as diuretics &#40;n&#61;12&#41; and antidepressants &#40;n&#61;11&#41;&#46;</p><p class="elsevierStylePara">In the follow-up 13 patients had died&#44; 11 had received a transplant and 11 had been transferred to another centre or had changed technique&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Overall natraemia tests</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In the recall period we carried out a total of 1802 sodium tests&#46; The mean value was 138 &#40;3&#46;2&#41; mEq&#47;l&#44; with a range between 122 and 147mEq&#47;l &#40;mean range 10&#46;5 &#91;4&#46;3&#93; mEq&#47;l&#41;&#46; Mean natraemia corrected for glucose was 139&#46;1 &#40;3&#46;6&#41; mEq&#47;l&#46; The difference between the two natraemias was statistically significant&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;0001&#46; Of the total tests carried out&#44; 215 &#40;11&#46;9&#37;&#41; were less than 135mEq&#47;l&#44; while 811 &#40;45&#37;&#41; were greater than 140mEq&#47;l&#46; Their distribution is displayed in Figure 1&#46;</p><p class="elsevierStylePara">To measure variability&#44; we first analysed the mean number of natraemias obtained for each patient&#44; which was 18&#46;7 &#40;4-34&#41;&#46; The mean CV of each patient &#40;for corrected natraemia&#41; was 2&#37; &#40;0&#46;8&#41; &#40;range&#58; 1&#37;-5&#46;6&#37;&#41;&#46; There was a negative correlation between natraemia and CV&#58; r&#61;-0&#46;63&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;0001&#46; As such&#44; when we carried out a separation based on natraemia tertiles &#40;Table 2&#41;&#44; it was highlighted that lower natraemias had a significantly higher CV&#44; SD and range&#46;</p><p class="elsevierStylePara">Lastly&#44; Table 3 displays the number of natraemias below 135 and above 140 recorded per patient&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Relationship between natraemias and clinical parameters</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Diabetics had a lower &#40;corrected&#41; natraemia than non-diabetics&#44; 138 &#40;2&#46;4&#41; compared with 139 &#40;2&#41; mEq&#47;l&#44; <span class="elsevierStyleItalic">P</span>&#60;&#46;003&#44; with CV of 2&#46;3 &#40;0&#46;9&#41; compared with 1&#46;9&#37; &#40;0&#46;7&#41; &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;01&#41; and SD of 3&#46;2 &#40;1&#46;2&#41; compared with 2&#46;5 &#40;0&#46;9&#41; mEq&#47;l &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;04&#41;&#46; There were no significant differences in range between the two groups&#46; IDG was not statistically different&#46;</p><p class="elsevierStylePara">We did not observe differences in natraemias according to sex&#44; age&#44; time on dialysis&#44; heart disease&#44; liver disease&#44; medication use or RRF &#40;Table 4&#41;&#46; Natraemia was not lower in those who had died during follow-up&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Relationship between natraemia and dialysis parameters</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We found a positive relationship between mean natraemia in each patient and total dialysate conductivity&#44; while the correlation between natraemia and IDG &#37; was negative&#46; There was no correlation between natraemia and pre-dialysis systolic and diastolic BP &#40;Table 5&#41;&#46; There were no differences in accordance with the dialysis technique used&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Comparison between direct and indirect potentiometry</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In a prospective control that included 59 patients&#44; we tested natraemia from the same extraction of pre-dialysis blood in both methods&#46;</p><p class="elsevierStylePara">Pearson&#8217;s correlation coefficient between the two methods was 0&#46;89 &#40;95&#37; confidence interval&#58; 0&#46;83-0&#46;93&#41; &#40;Figure 2&#41;&#46; Bland-Altman&#8217;s test showed that there were no significant differences&#59; we were able to confirm that at least 3&#37; of the data exceeded the two SD&#46; We found no statistical correlation between natraemia and glucose&#44; cholesterol or total protein concentration&#46; Proteins ranged from 5&#46;7 to 7&#46;2mg&#47;dl&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Relationship between natraemia and body volumes</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We tested 136 BCM measurements in 57 patients on whom we had carried out bioimpedance and extracted the samples in the same week&#46;</p><p class="elsevierStylePara">The mean values obtained were&#58; natraemia 139&#46;5 &#40;3&#46;1&#41; mEq&#47;l&#44; OH&#58; 1l &#40;-2&#46;8-8&#46;1&#41;&#44; OH&#47;ECV &#37;&#58; 6&#46;8 &#40;&#8211;16&#46;7-34&#46;2&#41;&#44; ECV 16l &#40;3&#46;4&#41;&#44; ECV &#37;&#47;weight 22&#37; &#40;3&#41;&#44; ICV 16&#46;3l &#40;4&#46;1&#41;&#44; ICV &#37;&#47;weight 22&#46;4&#37; &#40;4&#46;7&#41;&#44; ECV&#47;ICV&#58; 1 &#40;0&#46;1&#41;&#46; 16&#46;2&#37; of measurements displayed OH&#47;ECV &#37; values above 15&#37;&#46; We did not find any correlation between any of these parameters and natraemia at the time they were measured or when we separated them in accordance with this group&#8217;s natraemia tertiles &#40;Table 6&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Our study has three main results&#46; The first is that natraemia is not constant in all patients&#46; The second is that natraemia is positively related with dialysate conductivity and negatively with IDG &#37;&#46; The third result is that natraemia is not related to the distribution of body water&#44; which highlights the importance of separating the concepts of natraemia and volaemia&#46;</p><p class="elsevierStylePara">Until present&#44; three studies have stated that there is a sodium set-point or &#8220;fixed&#8221; natraemia in HD patients based on a low CV&#46; Our data confirm that natraemia has a CV that may be considered low mathematically but clinical practice &#40;Table 3&#41; and the wide range reveal that the sodium&#47;water relationship may change and may not be constant due to multiple factors&#46; This table clearly demonstrates the situation that we find daily in clinical practice&#44; since almost 60&#37; of patients had some sodium measurement that was less than 135 or more than 140mEq&#47;l&#46; By the same token&#44; Basile et al&#46;<span class="elsevierStyleSup">8 </span>found that despite a low CV&#44; the intraindividual range was 6&#46;2&#177;2&#46;9 and was higher than 10mEq&#47;l in 11 subjects&#46; In addition&#44; Peixoto et al&#46;<span class="elsevierStyleSup">6 </span>despite claiming that this set-point exists&#44; demonstrated that 21&#37; of patients had a range higher than 10mEq&#47;l&#46; Furthermore&#44; our results show that variability is higher in patients with natraemia of less than 138mEq&#47;l &#40;Table 2&#41;&#46; It is easy to observe from the physiological point of view that although thirst is very well regulated&#44; in daily life there are other non-physiological factors that modify liquid or salt intake and that make natraemia inconstant&#46; Strikingly&#44; CV is higher in diabetics&#44; which could be attributed to the fact that in this group&#44; thirst is stimulated in accordance with blood glucose&#44; although IDG is not statistically significant&#46; Although in previous studies the percentage of diabetics was high &#40;reaching 47&#37; in some studies<span class="elsevierStyleSup">6</span>&#41;&#44; until now&#44; this population had not been studied separately and furthermore it has a lower &#40;corrected&#41; natraemia <span class="elsevierStyleItalic">per se</span>&#46; This variability is important when evaluating natraemia as a mortality factor considered &#8220;constant&#8221; and determining its significance and the value to be selected for these studies and investigating whether there are differences in accordance with the studied populations&#46;</p><p class="elsevierStylePara">Out of the three studies cited regarding the set-point&#44; in two of them natraemia was measured with indirect potenciometry<span class="elsevierStyleSup">7&#44;9</span> and in the other with direct potentiometry&#46;<span class="elsevierStyleSup">8 </span>In normal clinical practice the method used is indirect potentiometry&#44; considered the reference for evaluating other methods&#46;<span class="elsevierStyleSup">23</span> Our results show an excellent correlation between the two methods and all the results were obtained in the same laboratory&#44; which complies with ISO standards&#46; In any case&#44; given that the method employed in most hospitals is indirect potentiometry&#44; we believe that our results are the most relevant and most applicable to clinical practice&#46;</p><p class="elsevierStylePara">In our study we did not find differences in natraemia in terms of the associated diseases or mortality&#44; which may be due to the fact that we had a small number of patients in comparison to the other large studies previously published and because we used a mean natraemia over a long follow-up period&#46; Only diabetic patients had lower corrected natraemias&#44; which we attribute to the abovementioned causes&#46;</p><p class="elsevierStylePara">In relation to the dialysis parameters&#44; we found an association between natraemia and total conductivity in the dialysate&#44; which had not been found in other studies&#46; These results must be interpreted while bearing in mind that it is a retrospective study of a unit in which we individualised dialysate conductivity on the basis of its potential effect on BP and IDG&#44; as was explained in the section &#8220;Material and Method&#8221;&#46; For example&#44; on the basis of the criteria of the year 2012&#58; 6&#37; of patients had a conductivity of 13&#46;6&#37;&#44; 18&#46;7&#37; had 13&#46;7&#44; 31&#46;8&#37; had 13&#46;8&#44; 24&#46;8&#37; had 13&#46;9&#44; 16&#46;9&#37; had 14 and 1&#46;5&#37; had 14&#46;1mS&#47;sec conductivity&#46; In the major studies cited&#44;<span class="elsevierStyleSup">3&#44;4</span> when they tried to explain the role that sodium selection in dialysate plays in mortality&#44; we found disparate results that were difficult to interpret&#46; They did find that sodium concentration in dialysate is related to IDG and BP&#44; but not to natraemia&#46; However&#44; in these studies&#44; the criteria for choosing the dialysate are unknown&#46; The effects of changing sodium concentration in dialysate on natraemia found in the literature are variable&#46; While this relationship is clear in the study by Manculu et al&#46;<span class="elsevierStyleSup">17</span>&#44; in which decreasing dialysate conductivity decreases initial plasma conductivity&#44; the results are different in the study by Paula et al&#46;<span class="elsevierStyleSup">24</span>&#46; If the differences are due to the latter being based on sodium that is calculated by machine&#44; this is not explained&#46; Many current monitors calculate sodium plasma concentration on the basis of ionic dialysance&#46; Although plasma natraemia and calculated natraemia are different&#44;<span class="elsevierStyleSup">25</span> their values are very useful in clinical practice&#46; The point is that when we act on dialysate conductivity to intervene in BP and IDG we modify the sodium balance by diffusion and as a result&#44; we influence natraemia&#46; We do not know the consequences of this action&#46; Since our study is retrospective&#44; we cannot know if lower natraemia is the cause or the consequence of choosing a dialysate with lower conductivity in accordance with clinical parameters&#46; On viewing the existing literature and our data&#44; when the dialysis regimen is modified &#40;changes in conductivity<span class="elsevierStyleSup">17</span> or frequency<span class="elsevierStyleSup">18</span>&#41; natraemia may vary&#46; As such&#44; if decreasing sodium conductivity to control BP or IDG has the result of decreasing natraemia&#44; it would be necessary to conduct new prospective studies to determine if the intended benefit might be offset by decreased natraemia&#46;</p><p class="elsevierStylePara">Natraemia was also negatively related to IDG &#37;&#46; This could be explained by these patients having more sodium gain than water&#44; highlighting the water&#47;sodium relationship&#44; or else because in those who had higher gains we tried to decrease sodium concentration in dialysate to limit the positive balance and thirst&#46; As with the previous point&#44; since this was a retrospective study we were unable to distinguish between cause and effect&#46;</p><p class="elsevierStylePara">Lastly&#44; we would like to comment on the bioimpedance results&#46; Contrary to what we theoretically thought we would find&#44; patients with hyponatraemia did not display a relative increase in ICV or differences in distribution between ECV and ICV or OH&#46; This finding highlights that&#44; like with the population with normal renal function&#44; we could find hyponatraemia with hyper&#47;hypo&#47;normovolaemia and this highlights the complexity of managing the balances volaemia &#40;&#61;sodium&#41; and natraemia &#40;&#61;water&#41; with HD&#46; Until now&#44; no publication had been written in this regard&#44; which means that our study is contributing very new information and is opening a field of research&#46;</p><p class="elsevierStylePara">As limitations to our results&#44; we have already mentioned that the retrospective nature is a confusing factor when it comes to interpreting the relationship between natraemia and dialysate conductivity and IDG &#37; but it does not affect the variability results for natraemia in a normal clinical practice in which the situation can change&#46; The small number of patients could explain why we did not find a difference in mortality or other epidemiological factors&#46; Lastly&#44; must say that we know bioimpedance is not a direct measure of different volumes but it is a very useful tool and one that is employed extensively in dialysis units to assess hydration&#46; As such&#44; although it is not the gold standard method for measuring body water&#44; its use has been validated and on the basis of daily practice&#44; we can say that its results on the absence of a relationship between hydration and natraemia are clear&#46;</p><p class="elsevierStylePara">In conclusion&#44; natraemia in HD patients has a low CV&#44; but it does not display a constant value&#44; especially in patients with a tendency for hyponatraemia and it is necessary to correct it for blood glucose&#46; This CV is higher in diabetics&#44; in whom natraemia is lower&#46; The lack of association between natraemia and volume highlights the need to independently assess the sodium and salt balances that each patient requires&#44; insisting once again on the importance of individualised HD&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52154&#95;en&#95;t18&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52154_en_t18.12217.jpg" alt="Factors involved in water and salt intake"></img></a></p><p class="elsevierStylePara">Table 1&#46; Factors involved in water and salt intake</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52155&#95;en&#95;t28&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52155_en_t28.12217.jpg" alt="Differences in the intraindividual coefficient of variation and standard deviation in accordance with natraemia tertiles"></img></a></p><p class="elsevierStylePara">Table 2&#46; Differences in the intraindividual coefficient of variation and standard deviation in accordance with natraemia tertiles</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52156&#95;en&#95;t38&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52156_en_t38.12217.jpg" alt="Distribution of patients in accordance with the natraemias found"></img></a></p><p class="elsevierStylePara">Table 3&#46; Distribution of patients in accordance with the natraemias found</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52157&#95;en&#95;t48&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52157_en_t48.12217.jpg" alt="Percentage of patients grouped by tertiles according to clinical characteristics"></img></a></p><p class="elsevierStylePara">Table 4&#46; Percentage of patients grouped by tertiles according to clinical characteristics</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52158&#95;en&#95;t58&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52158_en_t58.12217.jpg" alt="Mean natraemia correlation for each patient with conductivity used in the dialysate over one year and weight gain during this year"></img></a></p><p class="elsevierStylePara">Table 5&#46; Mean natraemia correlation for each patient with conductivity used in the dialysate over one year and weight gain during this year</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52159&#95;en&#95;t68&#46;12117&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52159_en_t68.12117.jpg" alt="Bioimpedance results in accordance with the natraemia tertiles "></img></a></p><p class="elsevierStylePara">Table 6&#46; Bioimpedance results in accordance with the natraemia tertiles </p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52160&#95;en&#95;f18&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52160_en_f18.12217.jpg" alt="Distribution of all natraemias measured &#40;n&#61;1802&#41;&#46;"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Distribution of all natraemias measured &#40;n&#61;1802&#41;&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12117&#95;16025&#95;52161&#95;en&#95;f28&#46;12217&#46;jpg" class="elsevierStyleCrossRefs"><img src="12117_16025_52161_en_f28.12217.jpg" alt="Relationship between direct and indirect potentiometry"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Relationship between direct and indirect potentiometry</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introducci&#243;n&#58;&#160;</span>La natremia en los pacientes en hemodi&#225;lisis &#40;HD&#41; se considera constante&#44; contrariamente a lo observado en la cl&#237;nica diaria&#46; Su relaci&#243;n con par&#225;metros cl&#237;nicos&#44; de di&#225;lisis y con la distribuci&#243;n del agua corporal &#40;AC&#41; no est&#225; aclarada&#46; <span class="elsevierStyleBold">Objetivos&#58;</span> Estudiar&#58; 1&#41; la variabilidad intrasujeto de la natremia&#44; 2&#41; la relaci&#243;n entre natremia y par&#225;metros cl&#237;nicos y dial&#237;ticos y 3&#41; la relaci&#243;n entre natremia y distribuci&#243;n del AC por bioimpedancia&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58;</span> Estudio observacional retrospectivo de 98 pacientes en HD cr&#243;nica&#46; Se recogieron caracter&#237;sticas cl&#237;nicas&#44; de HD&#44; natremia&#44; glucemia y medidas de bioimpedancia&#46; <span class="elsevierStyleBold">Resultados&#58;</span> Sesenta y tres varones y 35 mujeres de 69&#44;6 &#40;21-91&#41; a&#241;os con seguimiento de 23&#44;2 &#40;10&#41; meses&#46; Variabilidad&#58; 1802 determinaciones de sodio&#58; natremia media 138 &#40;3&#44;2&#41; y corregida para glucemia&#58; 139&#44;1 &#40;3&#44;6&#41; mEq&#47;l&#44; p&#160;&#60;&#160;0&#44;0001&#46; El coeficiente de variaci&#243;n &#40;CV&#41; intrasujeto fue 2 &#40;0&#44;8&#41;&#160;&#37; &#40;rango&#58; 1-5&#44;6&#160;&#37;&#41; y correlacion&#243; negativamente con la natremia &#40;r&#160;&#61;&#160;&#8211;0&#44;63&#44; p&#160;&#60;&#160;0&#44;0001&#41;&#46; Par&#225;metros cl&#237;nicos&#58; en diab&#233;ticos la natremia corregida era inferior a en no-diab&#233;ticos 138 &#40;2&#44;4&#41; frente a 139 &#40;2&#41; mEq&#47;l&#44; p&#160;&#60;&#160;0&#44;003&#44; con CV de 2&#44;3 &#40;0&#44;9&#41; frente a 1&#44;9 &#40;0&#44;7&#41;&#160;&#37; &#40;p&#160;&#60;&#160;0&#44;01&#41; y desviaci&#243;n est&#225;ndar de 3&#44;2 &#40;1&#44;2&#41; frente a 2&#44;5 &#40;0&#44;9&#41; mEq&#47;l &#40;p&#160;&#60;&#160;0&#44;04&#41;&#46;&#160;No encontramos diferencias seg&#250;n sexo&#44; edad&#44; tiempo en di&#225;lisis&#44; cardiopat&#237;a&#44; hepatopat&#237;a&#44; f&#225;rmacos&#44; funci&#243;n renal residual ni mortalidad&#46; Par&#225;metros de HD&#58; relaci&#243;n positiva entre natremia y conductividad del l&#237;quido de di&#225;lisis y negativa con ganancia de peso interdi&#225;lisis &#40;GID&#41;&#46; Bioimpedancia&#58; no relaci&#243;n entre distribuci&#243;n AC y natremia&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> La natremia var&#237;a en cada paciente y se relaciona positivamente con la conductividad y negativamente con la GID&#46; En diab&#233;ticos la natremia es m&#225;s baja y el CV es mayor&#46; No existe relaci&#243;n entre natremia y la distribuci&#243;n del AC&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span> Natraemia in haemodialysis &#40;HD&#41; patients is considered constant contrary to daily clinical observations&#46; Its relationship with clinical parameters&#44; dialysis parameters and body water &#40;BW&#41; distribution is not clear&#46; <span class="elsevierStyleBold">Objectives&#58;</span> The aims of this study were to know 1&#41; the intraindividual variability of natraemia&#44; 2&#41; the relationship between natraemia and clinical and dialysis parameters and 3&#41; the relationship between natraemia and BW distribution by bioimpedance&#46; <span class="elsevierStyleBold">Material and</span> <span class="elsevierStyleBold">Method&#58;</span> Observational retrospective study on 98 chronic HD patients&#46; Clinical&#44; HD and natraemia&#44; glucose and bioimpedance data were collected&#46; <span class="elsevierStyleBold">Results&#58;</span> We included 63 males and 35 females of 69&#46;6 &#40;21-91&#41; years of age&#44; with a follow-up of 23&#46;2 &#40;10&#41; months&#46; Variability&#58; 1802 sodium measurements&#58; mean natraemia 138 &#40;3&#46;2&#41; mEq&#47;l and corrected for glucose&#58; 139&#46;1 &#40;3&#46;6&#41; mEq&#47;l&#44; <span class="elsevierStyleItalic">p</span>&#60;&#46;0001&#46; Intraindividual coefficient of variation &#40;CV&#41; was 2&#37; &#40;0&#46;8&#41; &#40;range 1-5&#46;6&#37;&#41; and it correlated negatively with natraemia &#40;r&#61;-0&#46;63&#44; <span class="elsevierStyleItalic">p</span>&#60;&#46;0001&#41;&#46; Clinical parameters&#58; corrected natraemia was lower in diabetics than in non-diabetics 138 &#40;2&#46;4&#41; compared with 139 &#40;2&#41; mEq&#47;l&#44; <span class="elsevierStyleItalic">p</span>&#60;&#46;003&#44; CV 2&#46;3 &#40;0&#46;9&#41; compared with 1&#46;9 &#40;0&#46;7&#41;&#37; &#40;<span class="elsevierStyleItalic">p</span>&#60;&#46;01&#41; and SD 3&#46;2 &#40;1&#46;2&#41; compared with 2&#46;5 &#40;0&#46;9&#41; mEq&#47;l &#40;<span class="elsevierStyleItalic">p</span>&#60;&#46;04&#41;&#46; No differences according to gender&#44; age&#44; HD time&#44; cardiac or liver disease&#44; medication use&#44; residual renal function or mortality were found&#46; HD parameters&#58; a positive relationship was found between natraemia and total dialysate conductivity and it was negative with interdialysis weight gain &#40;IDG&#41;&#46; - Bioimpedance&#58; no relationship was found between natraemia and BW distribution&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> Natraemia varies in each patient and is related positively with conductivity and negatively with IDG&#46; In diabetics natraemia is lower and CV is higher&#46; There is no relationship between natraemia and BW distribution&#46;</p>"
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                  "referenciaCompleta" => "Hyponatremia. In: Halperin ML, Kamel K, Goldsteind M. Fluid, electrolyte and acid-base physiology: a problem-based approach. 4th ed. Philadelphia: Saunders Elsevier; 2010. pp. 314-67."
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                  "referenciaCompleta" => "Bernabeu Andreu F, Corcho Robleda M, Redondo Fernández M, Sivera Monzó L, Coca Martín M, Arribas Gómez I. Procedimiento de validación de magnitudes bioquímicas en un gasómetro. Aplicación al alcance flexible en la Norma ISO 15189. Rev Lab Clin 2010;3:58-62."
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                  "referenciaCompleta" => "De Paula FM, Peixoto AJ, Pinto LV, Dorigo D, Patricio PJ, Santos SF. Clinical consequences of an individualized dialysate sodium prescription in hemodialysis patients. Kidney Int 2004;66:1232-8. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15327422" target="_blank">[Pubmed]</a>"
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                  "referenciaCompleta" => "Albalate M, Pérez García R, de Sequera P, Ortega M, Puerta M, Alcázar R, et al. Comparación entre la concentración de sodio calculada por el monitor y la medida en el laboratorio pre y postdiálisis. Nefrologia 2012;32(Suppl 3):68A."
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Article information

ISSN: 20132514
Original language: English

DOI:10.3265/Nefrologia.pre2013.Sep.12117

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	5	8
2024 October	63	66	129
2024 September	56	65	121
2024 August	64	96	160
2024 July	62	54	116
2024 June	60	66	126
2024 May	68	47	115
2024 April	59	55	114
2024 March	47	40	87
2024 February	38	52	90
2024 January	33	34	67
2023 December	36	40	76
2023 November	47	69	116
2023 October	57	55	112
2023 September	40	53	93
2023 August	55	66	121
2023 July	67	68	135
2023 June	57	59	116
2023 May	64	54	118
2023 April	46	30	76
2023 March	73	48	121
2023 February	52	54	106
2023 January	61	47	108
2022 December	76	54	130
2022 November	68	54	122
2022 October	94	64	158
2022 September	60	56	116
2022 August	51	55	106
2022 July	71	59	130
2022 June	62	48	110
2022 May	97	45	142
2022 April	74	40	114
2022 March	63	56	119
2022 February	54	44	98
2022 January	72	37	109
2021 December	88	36	124
2021 November	60	33	93
2021 October	71	48	119
2021 September	77	41	118
2021 August	76	47	123
2021 July	67	33	100
2021 June	83	38	121
2021 May	52	35	87
2021 April	86	172	258
2021 March	92	46	138
2021 February	97	52	149
2021 January	89	29	118
2020 December	38	19	57
2020 November	44	15	59
2020 October	44	14	58
2020 September	45	19	64
2020 August	52	16	68
2020 July	82	11	93
2020 June	97	25	122
2020 May	67	23	90
2020 April	30	20	50
2020 March	36	18	54
2020 February	56	24	80
2020 January	59	33	92
2019 December	84	25	109
2019 November	62	27	89
2019 October	49	14	63
2019 September	57	15	72
2019 August	34	8	42
2019 July	58	25	83
2019 June	44	14	58
2019 May	67	21	88
2019 April	76	36	112
2019 March	55	21	76
2019 February	47	23	70
2019 January	49	22	71
2018 December	120	35	155
2018 November	150	22	172
2018 October	100	7	107
2018 September	93	21	114
2018 August	56	19	75
2018 July	66	15	81
2018 June	58	14	72
2018 May	58	19	77
2018 April	81	7	88
2018 March	64	10	74
2018 February	76	7	83
2018 January	74	9	83
2017 December	80	14	94
2017 November	64	13	77
2017 October	43	7	50
2017 September	59	13	72
2017 August	63	11	74
2017 July	54	14	68
2017 June	50	9	59
2017 May	60	14	74
2017 April	57	15	72
2017 March	48	15	63
2017 February	44	14	58
2017 January	35	12	47
2016 December	120	11	131
2016 November	119	16	135
2016 October	172	10	182
2016 September	206	9	215
2016 August	271	7	278
2016 July	233	12	245
2016 June	156	0	156
2016 May	164	0	164
2016 April	121	0	121
2016 March	125	0	125
2016 February	138	0	138
2016 January	147	0	147
2015 December	184	0	184
2015 November	122	0	122
2015 October	126	0	126
2015 September	130	0	130
2015 August	96	0	96
2015 July	97	0	97
2015 June	58	0	58
2015 May	63	0	63
2015 April	6	0	6

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