Polyuria in adults. A diagnostic approach based on pathophysiology

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A diagnostic approach based on pathophysiology" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "301" "paginaFinal" => "308" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "G. Ramírez-Guerrero, H. Müller-Ortiz, C. Pedreros-Rosales" "autores" => array:3 [ 0 => array:4 [ "nombre" => "G." "apellidos" => "Ramírez-Guerrero" "email" => array:1 [ 0 => "ramirezguerrero.g@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "H." "apellidos" => "Müller-Ortiz" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 2 => array:3 [ "nombre" => "C." 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Una aproximación diagnóstica basada en la fisiopatología" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1619 "Ancho" => 2091 "Tamanyo" => 168244 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Free water and electrolyte-free water clearance flowchart and formula. Cwater(e): electrolyte-free water clearance; Cosm: osmolar clearance; Ku: urine potassium; Nap: plasma sodium; NaU: urine sodium." ] ] ] "textoCompleto" => "IntroductionPolyuria is defined as an inappropriately high production of diuresis, usually greater than 3 L of urine in 24 h (or greater than 40 mL/kg in 24 h). Its prevalence in the hospital setting is estimated to range from 26% to 38%<a class="elsevierStyleCrossRefs" href="#bib0005">1–4</a>.The volume of diuresis mainly depends on the excretion of solutes and the nephrons’ capacity to concentrate or dilute urine. Thus, polyuria can be classified according to two mechanisms of production:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•A greater excretion of solutes, or osmotic diuresis, characterized by a urine osmolarity (Osmu) of greater than 300 mOsm/kg.</li><li class="elsevierStyleListItem" id="lsti0010">•An excessive elimination of water, or water diuresis, characterized by an Osmu of less than 150 mOsm/kg.</li></ul>If both mechanisms are present, the Osmu will be between 150 and 300 mOsm/kg, which indicates a condition called mixed polyuria<a class="elsevierStyleCrossRef" href="#bib0025">5</a>.Urine volume is directly related to the total number of osmoles excreted per day. The solutes involved in water excretion can be electrolytes (Na+, K+, Cl−, and Ca++) and nonelectrolytes such as urea, glucose, or others (mannitol)<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. The daily excretion of osmoles is estimated to be 10 mOsm/kg per day and they must be excreted in water. This volume of free water can increase significantly when the intake of solutes is greater than 900 mOsm/day<a class="elsevierStyleCrossRef" href="#bib0035">7</a> or decrease if the excretion of solutes decreases significantly.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>Polyuria can be incapacitating and severely affect quality of life, altering the sleep cycle and daily activities, and can even cause volume depletion and fluctuations in serum sodium levels. Therefore, polyuria is a challenge for clinicians, given that because it can be generated due to multiple causes, a diagnosis requires knowledge of the homeostasis of water balance, sodium, urine concentration mechanisms, and a quantitative analysis of urine losses through electrolyte-free water clearance. These concepts will help us understand the cause of the polyuria and identify appropriate treatment.We will briefly explain some aspects of the physiology of urine concentration, the determination of urine osmolarity, and the concept of free water loss in order to facilitate comprehension of the differential diagnosis of polyuria.Physiology of urine concentrationPlasma osmolarity (Osmp) is monitored by osmoreceptors located in the hypothalamus, which detect subtle changes in it. In response to an increase in Osmp, vasopressin, or antidiuretic hormone (ADH), is released. Vasopressin is produced in the hypothalamus and is released through the neurohypophysis to act on V2 receptors in the basal membrane of the principle cells of the collecting duct tubules. Its mechanism of action consists of increasing water reabsorption through transmembrane channels called aquaporins (specifically aquaporin 2)<a class="elsevierStyleCrossRef" href="#bib0020">4</a>. If there is a decrease in vasopressin production or the kidney is not sensitive to it, diabetes insipidus occurs. In this case, the Osmu will be very low in relation to the Osmp, which will be elevated.It is important to remember that the osmotic gradient for the movement of water through aquaporins depends on the concentration of solutes in the cells, interstitium, tubules, and vessels of the medulla. The osmotic gradient promotes the passage of water from the collecting duct tubules towards a more concentrated interstitium, provoking an increase in interstitial osmolality<a class="elsevierStyleCrossRef" href="#bib0045">9</a>. The main solutes involved in the osmotic gradient are sodium and urea. However, a precise mathematical model that evaluates the urea gradient has not been able to be developed.The clinical importance of this physiological knowledge lies in the fact that urinary concentration defects have been observed due to abnormalities in the transporters of urea and other small solutes (aquaglyceroporins). Both are overexpressed as a response to the increase in ADH<a class="elsevierStyleCrossRef" href="#bib0050">10</a>. This limits the interpretation of the water deprivation test for differentiating between diabetes insipidus and psychogenic polyuria (a psychiatric disorder induced by excessive water intake).On the other hand, polyuria that continues over time can generate a renal medulla concentration gradient washout, triggering a decrease in the maximum capacity for concentrating urine regardless of the polyuria’s primary cause and generating a relative resistance to ADH. Therefore, an absolute distinction between primary polydipsia and central diabetes insipidus or nephrogenic diabetes insipidus is often not able to be made.Determination of urine osmolarityUrine osmolarity is a measurement which expresses the total concentration of solutes and is defined as the number of osmoles (Osm) per liter of solute. Urine osmolarity (Osmu) can be measured using an osmometer or calculated using two formulas:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">1In the first formula, Osmu can be obtained by multiplying the last two urine density (UD) values by 35. It is important to correct for glycosuria (decrease UD by 0.004 for every g/dL) and for proteinuria (decrease UD by 0.003 for every g/dL)<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Osmu (mOsm/kg) = [urine density – 1000] × 35</li></ul>This formula is not valid if the patient is administered mannitol, piperacillin, carbenicillin, or carbapenems.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">2The second formula is based on the determination of urine electrolytes and urea without considering glycosuria<a class="elsevierStyleCrossRef" href="#bib0055">11</a>:Osmu (mOsm/kg) = [Nau + Ku] × 2 + [ureau/5.6]</li></ul>The use of these formulas is limited because urine is a complex mixture of organic and inorganic compounds that can cause variation in the results obtained by the different UD measurement methods. The Osmu formula calculated for UD has very disperse correction values (0.73–0.86) and is better in “clean samples,” that is, those without proteinuria or glycosuria<a class="elsevierStyleCrossRef" href="#bib0060">12</a>.What’s more, when the urine pH measured by a reactive strip is high, the UD will be falsely decreased and vice-versa. For this reason, this test is more reliable with a pH between 7 and 7.5<a class="elsevierStyleCrossRef" href="#bib0065">13</a>. Reactive strips indirectly measure specific gravity, assuming that the ionic and nonionic constituents of urine are at a constant proportion. This does not always happen in practice, given that ionic constituents can be disproportionately elevated in children (lower urea concentration) and with conditions such as proteinuria, hyperparathyroidism, and hypercalciuria<a class="elsevierStyleCrossRef" href="#bib0070">14</a>. In conclusion, these formulas are useful as an initial approach if we know their limitations and interpret them cautiously.Determination of free water lossesFree water clearance is the volume of water that must be removed or added to urine to make it isosmotic. When urine is hypotonic, free water clearance is positive, that is, the kidney is eliminating water from the organism. In this case, this would be the quantity of water that would have to be removed from the urine to make it isotonic.Urine free water losses can occur in the diluted urine of patients with concentration abnormalities or also in relatively concentrated urines, as occurs with the use of osmotic diuretics during recovery from acute kidney failure or due to excretion of highly osmolar content (elevated protein intake, administration of total parenteral nutrition, or hypercatabolic states). These latter conditions allow for explaining the onset and persistence of the hypernatremia these patients can present with<a class="elsevierStyleCrossRef" href="#bib0075">15</a>.To understand free water clearance, the total volume of urine (V) is conceptually separated into two components: one consisting of isosmotic urine that contains all the solutes (Cosm) and another that only contains water (Cwater) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The increase or decrease of this last component allows us to predict the plasma sodium concentration<a class="elsevierStyleCrossRef" href="#bib0080">16</a>. Mathematically, it is expressed in the following formula:<elsevierMultimedia ident="eq0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Osmolar clearance can be calculated using the general clearance formula:<elsevierMultimedia ident="eq0020"></elsevierMultimedia>Simplifying these equations, we obtain the free water clearance formula:<elsevierMultimedia ident="eq0025"></elsevierMultimedia>By definition, Cosm includes all osmoles. However, urea is not relevant to the generation of osmotic gradients because it is distributed in the intra- and extracellular space in equal concentrations; it easily crosses cell membranes and moves through specific transporters in the collector duct tubules. Therefore, the original formula was modified<a class="elsevierStyleCrossRef" href="#bib0085">17</a> to only include urine osmoles that affect plasma sodium concentration (Nap), called electrolyte-free water clearance or Cwater(e).The equation can be modified by replacing Osmp with Nap and Osmu with urine sodium and potassium (Nau + Ku):<elsevierMultimedia ident="eq0030"></elsevierMultimedia>In conclusion, if Nau + Ku is less than Nap, then the Cwater(e) formula will have a positive result, reflecting a loss of free water with a consequent hypernatremia with hypotonic urine. On the contrary, if Nau + Ku is greater than Nap, then Cwater(e) will be negative, reflecting an increase in free water with a consequent hyponatremia with hypertonic urine.This formula also allows for understanding that in mixed or osmolar polyurias, hypernatremia is generated by “diluted” urine. For example, in a patient with a high amount of urea excretion, the original equation would predict a negative water excretion and a decrease in Nap, but in fact in these cases, Nap increases, which can be predicted precisely by the latter equation.Polyuria due to water diuresisThe causes of polyuria in outpatients are most frequently classified as polyurias due to water diuresis. The three main causes are central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia or primary polydipsia (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The incidence of diabetes insipidus in the general population is three cases out of every 100,000 inhabitants, with a slightly higher incidence in men (60%) than women. Congenital nephrogenic diabetes insipidus is a very rare disease with an incidence of four cases out of every 1,000,000 males<a class="elsevierStyleCrossRef" href="#bib0090">18</a>.Psychogenic polydipsia is a defect in thirst control. It is caused by a dysfunction in the production or release of ADH and is not always accompanied by a psychiatric disorder. Psychogenic polydipsia is characterized by compulsive water consumption due to fear of dehydration or a belief that one’s health improves with excessive consumption. It can also be observed in patients with hypothalamic sequelae of cranioencephalic trauma, vascular diseases, or infiltrative diseases of the hypothalamus such as sarcoidosis<a class="elsevierStyleCrossRef" href="#bib0095">19</a>. Its incidence is not known, but it seems to primary affect women (80% of cases) and its onset occurs in the third decade of life. Up to 40% of patients with schizophrenia present with it<a class="elsevierStyleCrossRef" href="#bib0090">18</a>. Nevertheless, the prevalence of psychogenic polydipsia is increasing in the general population due to a belief in the beneficial health effects of high fluid consumption<a class="elsevierStyleCrossRef" href="#bib0100">20</a>.When polyuria is due to water diuresis, conducting a water deprivation test has classically been suggested in order to differentiate between diabetes insipidus and psychogenic polydipsia. This test, initially described by Miller et al. in 1970<a class="elsevierStyleCrossRef" href="#bib0105">21</a>, has demonstrated a limited diagnostic precision of 70%. It has even been found that just 41% of patients with psychogenic polydipsia have the correct diagnosis<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. For this reasons, other diagnostic methods such as magnetic resonance imaging of the hypophysis and copeptin measurements are used, achieving sensitivities and specificities of greater than 90% in differentiating between psychogenic polydipsia and partial central diabetes insipidus with each of these tests<a class="elsevierStyleCrossRef" href="#bib0005">1</a>.Copeptin is a glycopeptide formed by a chain of 39 amino acids. It is the terminal fraction of the provasopressin molecule (precursor of vasopressin or antidiuretic hormone). There is a high correlation between levels of copeptin and levels of vasopressin (coefficient of correlation 0.8). Due to the difficulty of measuring vasopressin levels, measurements of copeptin levels are used in clinical practice. Their blood values in normal individuals range from 1 to 12 pmol/L<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a>.Polyuria due to osmotic diuresis and/or mixed polyuriaThe most frequent cause of polyuria due to osmotic diuresis in outpatients is hyperglycemia. However, there are also cases due to consumption of nutritional supplements that are high in protein, mainly in athletes<a class="elsevierStyleCrossRef" href="#bib0120">24</a>.In order to diagnose polyuria due to osmotic diuresis or mixed polyuria, it is necessary to collect a 24-h urine sample and measure electrolytes, glucose, creatinine, and urea nitrogen. With these values, it is possible to calculate the daily excretion of osmoles and measure Osmu in order to detect solutes that generate intratubular water movement (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Daily osmole excretion (Osmu multiplied by 24-h urine volume) is the sum of the excretion of electrolyte and nonelectrolyte solutes, all expressed as milliosmoles per day. Then, the next step in the study is to determine the type of solute responsible for the polyuria (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The contribution of electrolytes to the polyuria can be estimated by multiplying the sum of Nau + Ku measured in a 24-h urine sample by 2, assuming that there are no other quantitatively significant cations in the daily excretion of osmoles<a class="elsevierStyleCrossRef" href="#bib0125">25</a>. Values greater than 600 mOsm/day suggest that electrolytes are the solutes that generate the polyuria whereas a value lower than 600 mOsm/day points toward the diuresis being due to a nonelectrolyte solute, typically glucose or urea, as we will explain later on.This can be confirmed if an osmometer-measured Osmu value is available; if there is concordance with the osmometer-measured Osmu value, the polyuria is due to electrolytes. On the contrary, if the osmometer-measured Osmu is greater than what is calculated using the formula, it can be assumed that it is an osmotic diuresis not mediated by electrolytes<a class="elsevierStyleCrossRef" href="#bib0025">5</a>.Polyuria due to electrolyte washout is usually measured by a sodium salt (often chloride) as a consequence of excessive administration of saline solution, intravenous sodium bicarbonate administration, excessive salt intake, or use of loop diuretics. However, there may be other possibilities. Measuring Nau, Ku, and urinary chloride (Clu) values can be of help, as these values are used to calculate the urine anion gap, which allows for searching for an anion other than chloride which may be associated with the sodium. The urine anion gap is calculated by adding sodium and potassium and subtracting chloride ([Nau + Ku] − [Clu]).A positive value indicates the presence of one or more anions apart from chloride in urine<a class="elsevierStyleCrossRef" href="#bib0130">26</a>. This anion tends to be bicarbonate, therefore a pH of around 7.4 indicates large quantities of this anion in the urine<a class="elsevierStyleCrossRef" href="#bib0135">27</a>. A urine pH value of less than 6.4 rules out the bicarbonate anion as the cause and makes it necessary to search for others, such as ketoacids and an excess of anions related to toxins or drugs such as salicylates<a class="elsevierStyleCrossRef" href="#bib0130">26</a>.Osmotic diuresis not mediated by electrolytes can be observed in patients who are catabolizing a large quantity of protein, whether due to enteral or parenteral nutrition, hypercatabolic states, or the resolution of obstructive uropathy. In these patients, the urea is dragged by the water. When this occurs, values of daily nonelectrolyte osmole excretion of less than 600 mOsm can be abnormal and be enough to generate polyuria, depending on patient's pathophysiological state. Urea nitrogen values of 0.7 g/dL or its equivalent of 1500 mg/dL of urine urea are able to generate solute diuresis<a class="elsevierStyleCrossRef" href="#bib0125">25</a>.In daily practice, particularly in critical care units, it should be suspected that these patients lose hypotonic fluid in the urine due to urea-induced osmotic diuresis. At the same time, these losses are replaced with isotonic fluids that are in fact hypertonic compared to their urine, resulting in an increase in sodium and secondary hypernatremia. In this case, it is again useful to calculate Cwater(e) as it allows for guiding the quantity of free water necessary for maintaining natremia at a desired value.Glucose becomes present in urine if there is a decrease in the capacity to reabsorb filtered glucose or when there are plasma glucose concentrations greater than 200–250 mg/dL (exceeding the maximum transport capacity of SGLT-2 and SLGT-1 transporters in the proximal tubule)<a class="elsevierStyleCrossRef" href="#bib0140">28</a>. The glycosuria observed in diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome can generate excretion of more than 833 mmol, corresponding to 150 g of glucose per day, which is able to produce an additional 1.7–2.8 L of urine<a class="elsevierStyleCrossRef" href="#bib0025">5</a>.In clinical studies, pharmacological inhibition of SGLT-2 generated an increase in urine volume just a few days after initiating treatment, leading to osmotic diuresis mediated by natriuresis with glycosuria, achieving an increase of 1–1.5 times the baseline level<a class="elsevierStyleCrossRef" href="#bib0145">29</a>.In these cases, the results of the urine study must be evaluated individually according to the clinical context<a class="elsevierStyleCrossRefs" href="#bib0130">26,30</a>. Likewise, it should be remembered that an approach using the Cwater(e) formula based on osmolarity (influenced by urea concentration) may not correctly evaluate the renal management of water<a class="elsevierStyleCrossRef" href="#bib0155">31</a>.Clinical case 1A 31-year-old male consulted for intense, progressive thirst that had been ongoing for six months, with consumption of 18 L of water per day associated with nocturia and polyuria of 18 L/day. He did not take protein supplements. Upon physical examination, he did not present with any relevant findings.The study found an Nap of 144 mEq/L, Osmp of 283 mOsm/kg, 24-h urine volume of 11,660 mL, and Osmu of 79 mOsm/kg. On the 24-h urine test, an Nau of 20 mEq/L and Ku of 6.8 mEq/L were found.As the Osmu was hypotonic—less than 150 mOsm/kg—the polyuria was due to water diuresis.Given that the patient had not increased water intake in association with a particular diet, did not have a psychiatric disease, and his levels of blood sodium were within the upper normal limits, a diagnosis of diabetes insipidus was proposed. A water deprivation test was performed to differentiate between central or nephrogenic diabetes insipidus or primary polydipsia (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). It was interpreted as polyuria due to water diuresis secondary to central diabetes insipidus.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>In the case of our patient, despite not having reached a concentration greater than 800 mOsm/kg, perhaps due to the mechanisms of medullary concentration washout secondary to the polyuria, an increase in the Osmu of greater than 50% was achieved, which was enough to diagnose central diabetes insipidus.When we calculated the electrolyte-free water clearance using the Cwater(e) equation, the result was positive: 6.6 mL/min. In other words, the patient had a loss of 9504 cc of free water in a total urine volume of 11,660 cc, concordant with the hypernatremia observed due to a large loss of free water.For the central diabetes insipidus study (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), magnetic resonance imaging of the sella turcica with gadolinium was performed to search for a CNS tumor. The results were suggestive of lymphocytic infundibular neurohypophysitis. Treatment was started with intranasal desmopressin with a good response; the natremia, urinary frequency, and thirst normalized.Clinical case 2An 85-year-old male with a medical history of benign prostatic hyperplasia. Consulted due to anuria and abdominal pain. Of note on the blood test were a plasma creatinine level of 8 mg/dL and a plasma urea level of 192.6 mg/dL. The kidney ultrasound showed bilateral hydroureteronephrosis.A urinary catheter was placed, which drained 5500 mL of urine in 90 min; an improvement in renal function was observed in the following days. Replacement was started with 0.9% saline solution at a ratio of 75% of the diuresis. However, polyuria of 6000 mL in 24 h persisted.The study found a Nap of 148 mEq/L, Osmp of 285 mOsm/kg, and Osmu of 289 mOsm/kg. The 24-h urine collection test showed a urine volume of 6000 mL, Nau of 110 mmol/L, Ku of 30 mmol/L, Clu of 149 mmol/L, and urea of 828.9 mg/dL, without glycosuria. The urine anion gap ([Nau + Ku] − [Clu]) was negative.Given that the Osmu was 289 mOsm/kg, it was considered to be mixed polyuria. To define the type of solute that generated the polyuria (electrolyte or nonelectrolyte), the total quantity of urine solutes in 24 h was estimated as electrolytes (Ue):<elsevierMultimedia ident="eq0035"></elsevierMultimedia><elsevierMultimedia ident="eq0040"></elsevierMultimedia>Upon comparing this value to the urine solute load—Osmu × 6 L (289 × 6)—the result was 1734 mOsm. Given the above, it can be concluded that out of the total solute load (1734 mOsm), 1680 mOsm corresponded to electrolytes. This indicates that it was polyuria due to electrolyte-dependent solutes.The next step in this clinical case was to determine the predominant electrolyte in the urine. This was obtained by calculating sodium and chloride excretion in the urine, which is obtained by multiplying the concentration of each of these electrolytes by the urine volume (in liters):<elsevierMultimedia ident="eq0045"></elsevierMultimedia><elsevierMultimedia ident="eq0050"></elsevierMultimedia>These values exceed the relatively normal figures for a patient who follows a typical American diet (Nau 150 mmol, Clu 120 mmol)<a class="elsevierStyleCrossRef" href="#bib0025">5</a>. Therefore, Nau and Clu were the main solutes in the patient’s urine. The above, together with the negative urine anion gap value, means that there was little excretion of nonchloride anions, which indicates that the mechanism of the polyuria was secondary to the administration of saline solution as a fluid replacement solution, which perpetuated the polyuria. In this case, there was no mechanism mediated by a nonelectrolyte solute (urea), as is expected in obstructive uropathy.The electrolyte-free water clearance calculated using the Cwater(e) equation was positive: 0.2 mL/min. In other words, there was a loss of 288 mL of free water in a total urine volume of 6000 mLc together with electrolyte-free water diuresis, which was concordant with the mild hypernatremia observed.ConclusionThe evaluation of polyuric states is a challenge in internal medicine due to a lack of familiarity with the formulas presented herein. However, their understanding and use allow us to organize the diagnostic study of polyurias and estimate free water losses with a very high degree of precision.Therefore, measured and calculated urine osmolarity, the estimation of daily urine osmole excretion, their nature, the water deprivation test in water and mixed polyurias, and electrolyte-free water clearance are essential diagnostic tests that must be included in the evaluation of polyuria-polydipsia syndrome.FundingThe research has not received specific grants from agencies in the public, commercial, or non-profit sectors.Conflicts of interestThe authors of this article have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1702222" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1506763" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1702221" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1506762" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Physiology of urine concentration" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Determination of urine osmolarity" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Determination of free water losses" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Polyuria due to water diuresis" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Polyuria due to osmotic diuresis and/or mixed polyuria" ] ] ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Clinical case 1" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Clinical case 2" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-16" "fechaAceptado" => "2021-03-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1506763" "palabras" => array:3 [ 0 => "Polyuria" 1 => "Hypernatremia" 2 => "Electrolyte free water clearance" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1506762" "palabras" => array:3 [ 0 => "Poliuria" 1 => "Hipernatremia" 2 => "Aclaramiento de agua libre de electrolitos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Polyuria is a common clinical condition characterized by a urine output that is inappropriately high (more than 3 L in 24 h) for the patient’s blood pressure and plasma sodium levels. From a pathophysiological point of view, it is classified into two types: polyuria due to a greater excretion of solutes (urine osmolality >300 mOsm/L) or due to an inability to increase solute concentration (urine osmolality <150 mOsm/L). Sometimes both mechanisms can coexist (urine osmolality 150–300 mOsm/L). Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of free water clearance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the case of osmotic polyuria." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La poliuria es una condición clínica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presión arterial y sodio plasmático del paciente (volumen de orina >3 L/24 h). Desde el punto de vista fisiopatológico se clasifica en 2 tipos: debido a una mayor excreción de solutos (osmolaridad urinaria >300 mOsm/L) o debido a una incapacidad de aumentar la concentración de solutos (osmolaridad urinaria <150 mOsm/L). En ocasiones pueden coexistir ambos mecanismos (osmolaridad urinaria 150–300 mOsm/L). La poliuria supone un reto diagnóstico y su tratamiento correcto exige una evaluación de la historia clínica, la determinación de la osmolaridad urinaria, la estimación del aclaramiento de agua libre, el uso de pruebas de deprivación hídrica en la poliuria acuosa y la medición de electrólitos en sangre y orina en el caso de la poliuria osmótica." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ramírez-Guerrero G, Müller-Ortiz H, Pedreros-Rosales C. Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología. Rev Clin Esp. 2022;222:301–308." ] ] "multimedia" => array:12 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1619 "Ancho" => 2091 "Tamanyo" => 168244 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Free water and electrolyte-free water clearance flowchart and formula. Cwater(e): electrolyte-free water clearance; Cosm: osmolar clearance; Ku: urine potassium; Nap: plasma sodium; NaU: urine sodium." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2054 "Ancho" => 3167 "Tamanyo" => 298983 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Suggested flowchart for the differential diagnosis of polyuria. UAG: urine anion gap. Difference in milliequivalents per liter between the sum of Nau + Ku and Clu; Ue: urine electrolytes. 2× (Nau + Ku)." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 855 "Ancho" => 1508 "Tamanyo" => 73690 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Water deprivation test. In the figure, it can be observed that the patient started the deprivation test with a reduced Osmu and continued with diluted urine despite 240 min of water deprivation. Following administration of desmopressin, a urine concentration appropriate for the Osmp was achieved." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "DKA: diabetic ketoacidosis; iSGLT-2: sodium/glucose cotransporter 2 inhibitors; ATN: acute tubular necrosis; HHS: hyperglycemic hyperosmolar syndrome; CNS: central nervous system; OU: obstructive uropathy." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osmotic \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Electrolytes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sodium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Infusion of iso- or hypertonic sodium chloride \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal sodium losses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chloride \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diuretics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bartter syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bicarbonate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exogenous administration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acetazolamide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ketoanion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DKA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nonelectrolyte \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glucose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exogenous loading \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DKA-HHS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">iSGLT-2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Urea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Exogenous loading, protein or amino acids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypercatabolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ATN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">After OU \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mannitol/sorbitol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Water \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Excess intake \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychogenic polydipsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Iatrogenic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diabetes insipidus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Central \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cranioencephalic trauma \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNS tumors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNS infections \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sheehan syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Subarachnoid hemorrhage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNS lupus \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sarcoidosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nephrogenic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypokalemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypercalciuria \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lithium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sarcoidosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sickle cell anemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Obstructive uropathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polycystic kidney disease \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2892436.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Causes of polyuria." ] ] 4 => array:5 [ "identificador" => "eq0015" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "V = Cosm + Cwater" ] ] 5 => array:5 [ "identificador" => "eq0020" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "Cosm = V × Osmu/Osmp" ] ] 6 => array:5 [ "identificador" => "eq0025" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "Cwater = V (1 − Osmu/Osmp)" ] ] 7 => array:5 [ "identificador" => "eq0030" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "Cwater(e) = V (1 − (Nau + Ku)/Nap)" ] ] 8 => array:5 [ "identificador" => "eq0035" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "[2 × (Nau + Ku)] × 24-h urine volume (L)" ] ] 9 => array:5 [ "identificador" => "eq0040" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "[2 × (110 + 30)] × 6 L = 1680 mOsm/24 h" ] ] 10 => array:5 [ "identificador" => "eq0045" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "Nau 110 mmol/L × 6 L = 660 mmol" ] ] 11 => array:5 [ "identificador" => "eq0050" "tipo" => "MULTIMEDIAFORMULA" "mostrarFloat" => false "mostrarDisplay" => true "Formula" => array:1 [ "Quimica" => "Clu 149 mmol/L × 6 L = 894 mmol" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polyuria-polydipsia syndrome: a diagnostic challenge" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. 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Polyuria in adults. A diagnostic approach based on pathophysiology

Poliuria en el adulto. Una aproximación diagnóstica basada en la fisiopatología

G. Ramírez-Guerreroa,b,

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ramirezguerrero.g@gmail.com

Corresponding author.

, H. Müller-Ortizc,d,e, C. Pedreros-Rosalesc,d,e

a Unidad de Diálisis y Trasplante Renal, Hospital Carlos Van Buren, Valparaíso, Chile

b Departamento de Medicina Interna, Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile

c Departamento de Medicina Interna, Facultad de Medicina, Universidad de Concepción, Concepción, Bío Bío, Chile

d Unidad de Nefrología, Diálisis y Trasplante, Hospital las Higueras de Talcahuano, Talcahuano, Bío Bío, Chile

e Instituto de Nefrología Concepción, Concepción, Bío Bío, Chile

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Free water and electrolyte-free water clearance flowchart and formula&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">C<span class="elsevierStyleInf">water</span>&#40;e&#41;&#58; electrolyte-free water clearance&#59; C<span class="elsevierStyleInf">osm</span>&#58; osmolar clearance&#59; K<span class="elsevierStyleInf">u</span>&#58; urine potassium&#59; Na<span class="elsevierStyleInf">p</span>&#58; plasma sodium&#59; Na<span class="elsevierStyleInf">U</span>&#58; urine sodium&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Polyuria is defined as an inappropriately high production of diuresis&#44; usually greater than 3&#160;L of urine in 24&#160;h &#40;or greater than 40&#160;mL&#47;kg in 24&#160;h&#41;&#46; Its prevalence in the hospital setting is estimated to range from 26&#37; to 38&#37;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;4</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The volume of diuresis mainly depends on the excretion of solutes and the nephrons&#8217; capacity to concentrate or dilute urine&#46; Thus&#44; polyuria can be classified according to two mechanisms of production&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">A greater excretion of solutes&#44; or osmotic diuresis&#44; characterized by a urine osmolarity &#40;Osm<span class="elsevierStyleInf">u</span>&#41; of greater than 300&#160;mOsm&#47;kg&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">An excessive elimination of water&#44; or water diuresis&#44; characterized by an Osm<span class="elsevierStyleInf">u</span> of less than 150&#160;mOsm&#47;kg&#46;</p></li></ul></p><p id="par0025" class="elsevierStylePara elsevierViewall">If both mechanisms are present&#44; the Osm<span class="elsevierStyleInf">u</span> will be between 150 and 300&#160;mOsm&#47;kg&#44; which indicates a condition called mixed polyuria<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Urine volume is directly related to the total number of osmoles excreted per day&#46; The solutes involved in water excretion can be electrolytes &#40;Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>&#44; Cl<span class="elsevierStyleSup">&#8722;</span>&#44; and Ca<span class="elsevierStyleSup">&#43;&#43;</span>&#41; and nonelectrolytes such as urea&#44; glucose&#44; or others &#40;mannitol&#41;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; The daily excretion of osmoles is estimated to be 10&#160;mOsm&#47;kg per day and they must be excreted in water&#46; This volume of free water can increase significantly when the intake of solutes is greater than 900&#160;mOsm&#47;day<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> or decrease if the excretion of solutes decreases significantly&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Polyuria can be incapacitating and severely affect quality of life&#44; altering the sleep cycle and daily activities&#44; and can even cause volume depletion and fluctuations in serum sodium levels&#46; Therefore&#44; polyuria is a challenge for clinicians&#44; given that because it can be generated due to multiple causes&#44; a diagnosis requires knowledge of the homeostasis of water balance&#44; sodium&#44; urine concentration mechanisms&#44; and a quantitative analysis of urine losses through electrolyte-free water clearance&#46; These concepts will help us understand the cause of the polyuria and identify appropriate treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We will briefly explain some aspects of the physiology of urine concentration&#44; the determination of urine osmolarity&#44; and the concept of free water loss in order to facilitate comprehension of the differential diagnosis of polyuria&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Physiology of urine concentration</span><p id="par0045" class="elsevierStylePara elsevierViewall">Plasma osmolarity &#40;Osm<span class="elsevierStyleInf">p</span>&#41; is monitored by osmoreceptors located in the hypothalamus&#44; which detect subtle changes in it&#46; In response to an increase in Osm<span class="elsevierStyleInf">p</span>&#44; vasopressin&#44; or antidiuretic hormone &#40;ADH&#41;&#44; is released&#46; Vasopressin is produced in the hypothalamus and is released through the neurohypophysis to act on V2 receptors in the basal membrane of the principle cells of the collecting duct tubules&#46; Its mechanism of action consists of increasing water reabsorption through transmembrane channels called aquaporins &#40;specifically aquaporin 2&#41;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46; If there is a decrease in vasopressin production or the kidney is not sensitive to it&#44; diabetes insipidus occurs&#46; In this case&#44; the Osm<span class="elsevierStyleInf">u</span> will be very low in relation to the Osm<span class="elsevierStyleInf">p</span>&#44; which will be elevated&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">It is important to remember that the osmotic gradient for the movement of water through aquaporins depends on the concentration of solutes in the cells&#44; interstitium&#44; tubules&#44; and vessels of the medulla&#46; The osmotic gradient promotes the passage of water from the collecting duct tubules towards a more concentrated interstitium&#44; provoking an increase in interstitial osmolality<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46; The main solutes involved in the osmotic gradient are sodium and urea&#46; However&#44; a precise mathematical model that evaluates the urea gradient has not been able to be developed&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The clinical importance of this physiological knowledge lies in the fact that urinary concentration defects have been observed due to abnormalities in the transporters of urea and other small solutes &#40;aquaglyceroporins&#41;&#46; Both are overexpressed as a response to the increase in ADH<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>&#46; This limits the interpretation of the water deprivation test for differentiating between diabetes insipidus and psychogenic polyuria &#40;a psychiatric disorder induced by excessive water intake&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">On the other hand&#44; polyuria that continues over time can generate a renal medulla concentration gradient washout&#44; triggering a decrease in the maximum capacity for concentrating urine regardless of the polyuria&#8217;s primary cause and generating a relative resistance to ADH&#46; Therefore&#44; an absolute distinction between primary polydipsia and central diabetes insipidus or nephrogenic diabetes insipidus is often not able to be made&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Determination of urine osmolarity</span><p id="par0065" class="elsevierStylePara elsevierViewall">Urine osmolarity is a measurement which expresses the total concentration of solutes and is defined as the number of osmoles &#40;Osm&#41; per liter of solute&#46; Urine osmolarity &#40;Osm<span class="elsevierStyleInf">u</span>&#41; can be measured using an osmometer or calculated using two formulas&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1</span><p id="par0070" class="elsevierStylePara elsevierViewall">In the first formula&#44; Osm<span class="elsevierStyleInf">u</span> can be obtained by multiplying the last two urine density &#40;UD&#41; values by 35&#46; It is important to correct for glycosuria &#40;decrease UD by 0&#46;004 for every g&#47;dL&#41; and for proteinuria &#40;decrease UD by 0&#46;003 for every g&#47;dL&#41;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0071" class="elsevierStylePara elsevierViewall">Osm<span class="elsevierStyleInf">u</span> &#40;mOsm&#47;kg&#41;&#160;&#61;&#160;&#91;urine density&#160;&#8211;&#160;1000&#93;&#160;&#215;&#160;35</p></li></ul></p><p id="par0075" class="elsevierStylePara elsevierViewall">This formula is not valid if the patient is administered mannitol&#44; piperacillin&#44; carbenicillin&#44; or carbapenems&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2</span><p id="par0080" class="elsevierStylePara elsevierViewall">The second formula is based on the determination of urine electrolytes and urea without considering glycosuria<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>&#58;</p><p id="par0081" class="elsevierStylePara elsevierViewall">Osm<span class="elsevierStyleInf">u</span> &#40;mOsm&#47;kg&#41;&#160;&#61;&#160;&#91;Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span>&#93;&#160;&#215;&#160;2&#160;&#43;&#160;&#91;urea<span class="elsevierStyleInf">u</span>&#47;5&#46;6&#93;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">The use of these formulas is limited because urine is a complex mixture of organic and inorganic compounds that can cause variation in the results obtained by the different UD measurement methods&#46; The Osm<span class="elsevierStyleInf">u</span> formula calculated for UD has very disperse correction values &#40;0&#46;73&#8211;0&#46;86&#41; and is better in &#8220;clean samples&#44;&#8221; that is&#44; those without proteinuria or glycosuria<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">What&#8217;s more&#44; when the urine pH measured by a reactive strip is high&#44; the UD will be falsely decreased and vice-versa&#46; For this reason&#44; this test is more reliable with a pH between 7 and 7&#46;5<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a>&#46; Reactive strips indirectly measure specific gravity&#44; assuming that the ionic and nonionic constituents of urine are at a constant proportion&#46; This does not always happen in practice&#44; given that ionic constituents can be disproportionately elevated in children &#40;lower urea concentration&#41; and with conditions such as proteinuria&#44; hyperparathyroidism&#44; and hypercalciuria<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; In conclusion&#44; these formulas are useful as an initial approach if we know their limitations and interpret them cautiously&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Determination of free water losses</span><p id="par0095" class="elsevierStylePara elsevierViewall">Free water clearance is the volume of water that must be removed or added to urine to make it isosmotic&#46; When urine is hypotonic&#44; free water clearance is positive&#44; that is&#44; the kidney is eliminating water from the organism&#46; In this case&#44; this would be the quantity of water that would have to be removed from the urine to make it isotonic&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Urine free water losses can occur in the diluted urine of patients with concentration abnormalities or also in relatively concentrated urines&#44; as occurs with the use of osmotic diuretics during recovery from acute kidney failure or due to excretion of highly osmolar content &#40;elevated protein intake&#44; administration of total parenteral nutrition&#44; or hypercatabolic states&#41;&#46; These latter conditions allow for explaining the onset and persistence of the hypernatremia these patients can present with<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">To understand free water clearance&#44; the total volume of urine &#40;V&#41; is conceptually separated into two components&#58; one consisting of isosmotic urine that contains all the solutes &#40;C<span class="elsevierStyleInf">osm</span>&#41; and another that only contains water &#40;C<span class="elsevierStyleInf">water</span>&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The increase or decrease of this last component allows us to predict the plasma sodium concentration<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#46; Mathematically&#44; it is expressed in the following formula&#58;<elsevierMultimedia ident="eq0015"></elsevierMultimedia></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Osmolar clearance can be calculated using the general clearance formula&#58;<elsevierMultimedia ident="eq0020"></elsevierMultimedia></p><p id="par0115" class="elsevierStylePara elsevierViewall">Simplifying these equations&#44; we obtain the free water clearance formula&#58;<elsevierMultimedia ident="eq0025"></elsevierMultimedia></p><p id="par0120" class="elsevierStylePara elsevierViewall">By definition&#44; C<span class="elsevierStyleInf">osm</span> includes all osmoles&#46; However&#44; urea is not relevant to the generation of osmotic gradients because it is distributed in the intra- and extracellular space in equal concentrations&#59; it easily crosses cell membranes and moves through specific transporters in the collector duct tubules&#46; Therefore&#44; the original formula was modified<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> to only include urine osmoles that affect plasma sodium concentration &#40;Na<span class="elsevierStyleInf">p</span>&#41;&#44; called electrolyte-free water clearance or C<span class="elsevierStyleInf">water</span>&#40;e&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The equation can be modified by replacing Osm<span class="elsevierStyleInf">p</span> with Na<span class="elsevierStyleInf">p</span> and Osm<span class="elsevierStyleInf">u</span> with urine sodium and potassium &#40;Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span>&#41;&#58;<elsevierMultimedia ident="eq0030"></elsevierMultimedia></p><p id="par0130" class="elsevierStylePara elsevierViewall">In conclusion&#44; if Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span> is less than Na<span class="elsevierStyleInf">p</span>&#44; then the C<span class="elsevierStyleInf">water</span>&#40;e&#41; formula will have a positive result&#44; reflecting a loss of free water with a consequent hypernatremia with hypotonic urine&#46; On the contrary&#44; if Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span> is greater than Na<span class="elsevierStyleInf">p</span>&#44; then C<span class="elsevierStyleInf">water</span>&#40;e&#41; will be negative&#44; reflecting an increase in free water with a consequent hyponatremia with hypertonic urine&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">This formula also allows for understanding that in mixed or osmolar polyurias&#44; hypernatremia is generated by &#8220;diluted&#8221; urine&#46; For example&#44; in a patient with a high amount of urea excretion&#44; the original equation would predict a negative water excretion and a decrease in Na<span class="elsevierStyleInf">p</span>&#44; but in fact in these cases&#44; Na<span class="elsevierStyleInf">p</span> increases&#44; which can be predicted precisely by the latter equation&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Polyuria due to water diuresis</span><p id="par0140" class="elsevierStylePara elsevierViewall">The causes of polyuria in outpatients are most frequently classified as polyurias due to water diuresis&#46; The three main causes are central diabetes insipidus&#44; nephrogenic diabetes insipidus&#44; and psychogenic polydipsia or primary polydipsia &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">The incidence of diabetes insipidus in the general population is three cases out of every 100&#44;000 inhabitants&#44; with a slightly higher incidence in men &#40;60&#37;&#41; than women&#46; Congenital nephrogenic diabetes insipidus is a very rare disease with an incidence of four cases out of every 1&#44;000&#44;000 males<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Psychogenic polydipsia is a defect in thirst control&#46; It is caused by a dysfunction in the production or release of ADH and is not always accompanied by a psychiatric disorder&#46; Psychogenic polydipsia is characterized by compulsive water consumption due to fear of dehydration or a belief that one&#8217;s health improves with excessive consumption&#46; It can also be observed in patients with hypothalamic sequelae of cranioencephalic trauma&#44; vascular diseases&#44; or infiltrative diseases of the hypothalamus such as sarcoidosis<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&#46; Its incidence is not known&#44; but it seems to primary affect women &#40;80&#37; of cases&#41; and its onset occurs in the third decade of life&#46; Up to 40&#37; of patients with schizophrenia present with it<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46; Nevertheless&#44; the prevalence of psychogenic polydipsia is increasing in the general population due to a belief in the beneficial health effects of high fluid consumption<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">When polyuria is due to water diuresis&#44; conducting a water deprivation test has classically been suggested in order to differentiate between diabetes insipidus and psychogenic polydipsia&#46; This test&#44; initially described by Miller et al&#46; in 1970<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#44; has demonstrated a limited diagnostic precision of 70&#37;&#46; It has even been found that just 41&#37; of patients with psychogenic polydipsia have the correct diagnosis<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46; For this reasons&#44; other diagnostic methods such as magnetic resonance imaging of the hypophysis and copeptin measurements are used&#44; achieving sensitivities and specificities of greater than 90&#37; in differentiating between psychogenic polydipsia and partial central diabetes insipidus with each of these tests<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Copeptin is a glycopeptide formed by a chain of 39 amino acids&#46; It is the terminal fraction of the provasopressin molecule &#40;precursor of vasopressin or antidiuretic hormone&#41;&#46; There is a high correlation between levels of copeptin and levels of vasopressin &#40;coefficient of correlation 0&#46;8&#41;&#46; Due to the difficulty of measuring vasopressin levels&#44; measurements of copeptin levels are used in clinical practice&#46; Their blood values in normal individuals range from 1 to 12&#160;pmol&#47;L<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Polyuria due to osmotic diuresis and&#47;or mixed polyuria</span><p id="par0165" class="elsevierStylePara elsevierViewall">The most frequent cause of polyuria due to osmotic diuresis in outpatients is hyperglycemia&#46; However&#44; there are also cases due to consumption of nutritional supplements that are high in protein&#44; mainly in athletes<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In order to diagnose polyuria due to osmotic diuresis or mixed polyuria&#44; it is necessary to collect a 24-h urine sample and measure electrolytes&#44; glucose&#44; creatinine&#44; and urea nitrogen&#46; With these values&#44; it is possible to calculate the daily excretion of osmoles and measure Osm<span class="elsevierStyleInf">u</span> in order to detect solutes that generate intratubular water movement &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Daily osmole excretion &#40;Osm<span class="elsevierStyleInf">u</span> multiplied by 24-h urine volume&#41; is the sum of the excretion of electrolyte and nonelectrolyte solutes&#44; all expressed as milliosmoles per day&#46; Then&#44; the next step in the study is to determine the type of solute responsible for the polyuria &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">The contribution of electrolytes to the polyuria can be estimated by multiplying the sum of Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span> measured in a 24-h urine sample by 2&#44; assuming that there are no other quantitatively significant cations in the daily excretion of osmoles<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46; Values greater than 600&#160;mOsm&#47;day suggest that electrolytes are the solutes that generate the polyuria whereas a value lower than 600&#160;mOsm&#47;day points toward the diuresis being due to a nonelectrolyte solute&#44; typically glucose or urea&#44; as we will explain later on&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">This can be confirmed if an osmometer-measured Osm<span class="elsevierStyleInf">u</span> value is available&#59; if there is concordance with the osmometer-measured Osm<span class="elsevierStyleInf">u</span> value&#44; the polyuria is due to electrolytes&#46; On the contrary&#44; if the osmometer-measured Osm<span class="elsevierStyleInf">u</span> is greater than what is calculated using the formula&#44; it can be assumed that it is an osmotic diuresis not mediated by electrolytes<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Polyuria due to electrolyte washout is usually measured by a sodium salt &#40;often chloride&#41; as a consequence of excessive administration of saline solution&#44; intravenous sodium bicarbonate administration&#44; excessive salt intake&#44; or use of loop diuretics&#46; However&#44; there may be other possibilities&#46; Measuring Na<span class="elsevierStyleInf">u</span>&#44; K<span class="elsevierStyleInf">u</span>&#44; and urinary chloride &#40;Cl<span class="elsevierStyleInf">u</span>&#41; values can be of help&#44; as these values are used to calculate the urine anion gap&#44; which allows for searching for an anion other than chloride which may be associated with the sodium&#46; The urine anion gap is calculated by adding sodium and potassium and subtracting chloride &#40;&#91;Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span>&#93;&#160;&#8722;&#160;&#91;Cl<span class="elsevierStyleInf">u</span>&#93;&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">A positive value indicates the presence of one or more anions apart from chloride in urine<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46; This anion tends to be bicarbonate&#44; therefore a pH of around 7&#46;4 indicates large quantities of this anion in the urine<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46; A urine pH value of less than 6&#46;4 rules out the bicarbonate anion as the cause and makes it necessary to search for others&#44; such as ketoacids and an excess of anions related to toxins or drugs such as salicylates<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Osmotic diuresis not mediated by electrolytes can be observed in patients who are catabolizing a large quantity of protein&#44; whether due to enteral or parenteral nutrition&#44; hypercatabolic states&#44; or the resolution of obstructive uropathy&#46; In these patients&#44; the urea is dragged by the water&#46; When this occurs&#44; values of daily nonelectrolyte osmole excretion of less than 600&#160;mOsm can be abnormal and be enough to generate polyuria&#44; depending on patient&#39;s pathophysiological state&#46; Urea nitrogen values of 0&#46;7&#160;g&#47;dL or its equivalent of 1500&#160;mg&#47;dL of urine urea are able to generate solute diuresis<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">In daily practice&#44; particularly in critical care units&#44; it should be suspected that these patients lose hypotonic fluid in the urine due to urea-induced osmotic diuresis&#46; At the same time&#44; these losses are replaced with isotonic fluids that are in fact hypertonic compared to their urine&#44; resulting in an increase in sodium and secondary hypernatremia&#46; In this case&#44; it is again useful to calculate C<span class="elsevierStyleInf">water</span>&#40;e&#41; as it allows for guiding the quantity of free water necessary for maintaining natremia at a desired value&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Glucose becomes present in urine if there is a decrease in the capacity to reabsorb filtered glucose or when there are plasma glucose concentrations greater than 200&#8211;250&#160;mg&#47;dL &#40;exceeding the maximum transport capacity of SGLT-2 and SLGT-1 transporters in the proximal tubule&#41;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46; The glycosuria observed in diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome can generate excretion of more than 833&#160;mmol&#44; corresponding to 150&#160;g of glucose per day&#44; which is able to produce an additional 1&#46;7&#8211;2&#46;8&#160;L of urine<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In clinical studies&#44; pharmacological inhibition of SGLT-2 generated an increase in urine volume just a few days after initiating treatment&#44; leading to osmotic diuresis mediated by natriuresis with glycosuria&#44; achieving an increase of 1&#8211;1&#46;5 times the baseline level<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">In these cases&#44; the results of the urine study must be evaluated individually according to the clinical context<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;30</span></a>&#46; Likewise&#44; it should be remembered that an approach using the C<span class="elsevierStyleInf">water</span>&#40;e&#41; formula based on osmolarity &#40;influenced by urea concentration&#41; may not correctly evaluate the renal management of water<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Clinical case 1</span><p id="par0225" class="elsevierStylePara elsevierViewall">A 31-year-old male consulted for intense&#44; progressive thirst that had been ongoing for six months&#44; with consumption of 18&#160;L of water per day associated with nocturia and polyuria of 18&#160;L&#47;day&#46; He did not take protein supplements&#46; Upon physical examination&#44; he did not present with any relevant findings&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The study found an Na<span class="elsevierStyleInf">p</span> of 144&#160;mEq&#47;L&#44; Osm<span class="elsevierStyleInf">p</span> of 283&#160;mOsm&#47;kg&#44; 24-h urine volume of 11&#44;660&#160;mL&#44; and Osm<span class="elsevierStyleInf">u</span> of 79&#160;mOsm&#47;kg&#46; On the 24-h urine test&#44; an Na<span class="elsevierStyleInf">u</span> of 20&#160;mEq&#47;L and K<span class="elsevierStyleInf">u</span> of 6&#46;8&#160;mEq&#47;L were found&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">As the Osm<span class="elsevierStyleInf">u</span> was hypotonic&#8212;less than 150&#160;mOsm&#47;kg&#8212;the polyuria was due to water diuresis&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Given that the patient had not increased water intake in association with a particular diet&#44; did not have a psychiatric disease&#44; and his levels of blood sodium were within the upper normal limits&#44; a diagnosis of diabetes insipidus was proposed&#46; A water deprivation test was performed to differentiate between central or nephrogenic diabetes insipidus or primary polydipsia &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; It was interpreted as polyuria due to water diuresis secondary to central diabetes insipidus&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0245" class="elsevierStylePara elsevierViewall">In the case of our patient&#44; despite not having reached a concentration greater than 800&#160;mOsm&#47;kg&#44; perhaps due to the mechanisms of medullary concentration washout secondary to the polyuria&#44; an increase in the Osm<span class="elsevierStyleInf">u</span> of greater than 50&#37; was achieved&#44; which was enough to diagnose central diabetes insipidus&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">When we calculated the electrolyte-free water clearance using the C<span class="elsevierStyleInf">water</span>&#40;e&#41; equation&#44; the result was positive&#58; 6&#46;6&#160;mL&#47;min&#46; In other words&#44; the patient had a loss of 9504 cc of free water in a total urine volume of 11&#44;660 cc&#44; concordant with the hypernatremia observed due to a large loss of free water&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">For the central diabetes insipidus study &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; magnetic resonance imaging of the sella turcica with gadolinium was performed to search for a CNS tumor&#46; The results were suggestive of lymphocytic infundibular neurohypophysitis&#46; Treatment was started with intranasal desmopressin with a good response&#59; the natremia&#44; urinary frequency&#44; and thirst normalized&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Clinical case 2</span><p id="par0260" class="elsevierStylePara elsevierViewall">An 85-year-old male with a medical history of benign prostatic hyperplasia&#46; Consulted due to anuria and abdominal pain&#46; Of note on the blood test were a plasma creatinine level of 8&#160;mg&#47;dL and a plasma urea level of 192&#46;6&#160;mg&#47;dL&#46; The kidney ultrasound showed bilateral hydroureteronephrosis&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">A urinary catheter was placed&#44; which drained 5500&#160;mL of urine in 90&#160;min&#59; an improvement in renal function was observed in the following days&#46; Replacement was started with 0&#46;9&#37; saline solution at a ratio of 75&#37; of the diuresis&#46; However&#44; polyuria of 6000&#160;mL in 24&#160;h persisted&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The study found a Na<span class="elsevierStyleInf">p</span> of 148&#160;mEq&#47;L&#44; Osm<span class="elsevierStyleInf">p</span> of 285&#160;mOsm&#47;kg&#44; and Osm<span class="elsevierStyleInf">u</span> of 289&#160;mOsm&#47;kg&#46; The 24-h urine collection test showed a urine volume of 6000&#160;mL&#44; Na<span class="elsevierStyleInf">u</span> of 110&#160;mmol&#47;L&#44; K<span class="elsevierStyleInf">u</span> of 30&#160;mmol&#47;L&#44; Cl<span class="elsevierStyleInf">u</span> of 149&#160;mmol&#47;L&#44; and urea of 828&#46;9&#160;mg&#47;dL&#44; without glycosuria&#46; The urine anion gap &#40;&#91;Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span>&#93;&#160;&#8722;&#160;&#91;Cl<span class="elsevierStyleInf">u</span>&#93;&#41; was negative&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Given that the Osm<span class="elsevierStyleInf">u</span> was 289&#160;mOsm&#47;kg&#44; it was considered to be mixed polyuria&#46; To define the type of solute that generated the polyuria &#40;electrolyte or nonelectrolyte&#41;&#44; the total quantity of urine solutes in 24&#160;h was estimated as electrolytes &#40;Ue&#41;&#58;<elsevierMultimedia ident="eq0035"></elsevierMultimedia><elsevierMultimedia ident="eq0040"></elsevierMultimedia></p><p id="par0280" class="elsevierStylePara elsevierViewall">Upon comparing this value to the urine solute load&#8212;Osm<span class="elsevierStyleInf">u</span>&#160;&#215;&#160;6&#160;L &#40;289&#160;&#215;&#160;6&#41;&#8212;the result was 1734&#160;mOsm&#46; Given the above&#44; it can be concluded that out of the total solute load &#40;1734&#160;mOsm&#41;&#44; 1680&#160;mOsm corresponded to electrolytes&#46; This indicates that it was polyuria due to electrolyte-dependent solutes&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">The next step in this clinical case was to determine the predominant electrolyte in the urine&#46; This was obtained by calculating sodium and chloride excretion in the urine&#44; which is obtained by multiplying the concentration of each of these electrolytes by the urine volume &#40;in liters&#41;&#58;<elsevierMultimedia ident="eq0045"></elsevierMultimedia><elsevierMultimedia ident="eq0050"></elsevierMultimedia></p><p id="par0290" class="elsevierStylePara elsevierViewall">These values exceed the relatively normal figures for a patient who follows a typical American diet &#40;Na<span class="elsevierStyleInf">u</span> 150&#160;mmol&#44; Cl<span class="elsevierStyleInf">u</span> 120&#160;mmol&#41;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; Therefore&#44; Na<span class="elsevierStyleInf">u</span> and Cl<span class="elsevierStyleInf">u</span> were the main solutes in the patient&#8217;s urine&#46; The above&#44; together with the negative urine anion gap value&#44; means that there was little excretion of nonchloride anions&#44; which indicates that the mechanism of the polyuria was secondary to the administration of saline solution as a fluid replacement solution&#44; which perpetuated the polyuria&#46; In this case&#44; there was no mechanism mediated by a nonelectrolyte solute &#40;urea&#41;&#44; as is expected in obstructive uropathy&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">The electrolyte-free water clearance calculated using the C<span class="elsevierStyleInf">water</span>&#40;e&#41; equation was positive&#58; 0&#46;2&#160;mL&#47;min&#46; In other words&#44; there was a loss of 288&#160;mL of free water in a total urine volume of 6000&#160;mLc together with electrolyte-free water diuresis&#44; which was concordant with the mild hypernatremia observed&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusion</span><p id="par0300" class="elsevierStylePara elsevierViewall">The evaluation of polyuric states is a challenge in internal medicine due to a lack of familiarity with the formulas presented herein&#46; However&#44; their understanding and use allow us to organize the diagnostic study of polyurias and estimate free water losses with a very high degree of precision&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">Therefore&#44; measured and calculated urine osmolarity&#44; the estimation of daily urine osmole excretion&#44; their nature&#44; the water deprivation test in water and mixed polyurias&#44; and electrolyte-free water clearance are essential diagnostic tests that must be included in the evaluation of polyuria-polydipsia syndrome&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Funding</span><p id="par0310" class="elsevierStylePara elsevierViewall">The research has not received specific grants from agencies in the public&#44; commercial&#44; or non-profit sectors&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0315" class="elsevierStylePara elsevierViewall">The authors of this article have no conflicts of interest to declare&#46;</p></span></span>"
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              "titulo" => "Physiology of urine concentration"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Polyuria is a common clinical condition characterized by a urine output that is inappropriately high &#40;more than 3&#160;L in 24&#160;h&#41; for the patient&#8217;s blood pressure and plasma sodium levels&#46; From a pathophysiological point of view&#44; it is classified into two types&#58; polyuria due to a greater excretion of solutes &#40;urine osmolality &#62;300&#160;mOsm&#47;L&#41; or due to an inability to increase solute concentration &#40;urine osmolality &#60;150&#160;mOsm&#47;L&#41;&#46; Sometimes both mechanisms can coexist &#40;urine osmolality 150&#8211;300&#160;mOsm&#47;L&#41;&#46; Polyuria is a diagnostic challenge and its proper treatment requires an evaluation of the medical record&#44; determination of urine osmolality&#44; estimation of free water clearance&#44; use of water deprivation tests in aqueous polyuria&#44; and measurement of electrolytes in blood and urine in the case of osmotic polyuria&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La poliuria es una condici&#243;n cl&#237;nica frecuente caracterizada por un volumen de orina inapropiadamente alto para los niveles de presi&#243;n arterial y sodio plasm&#225;tico del paciente &#40;volumen de orina &#62;3&#160;L&#47;24&#160;h&#41;&#46; Desde el punto de vista fisiopatol&#243;gico se clasifica en 2 tipos&#58; debido a una mayor excreci&#243;n de solutos &#40;osmolaridad urinaria &#62;300&#160;mOsm&#47;L&#41; o debido a una incapacidad de aumentar la concentraci&#243;n de solutos &#40;osmolaridad urinaria &#60;150&#160;mOsm&#47;L&#41;&#46; En ocasiones pueden coexistir ambos mecanismos &#40;osmolaridad urinaria 150&#8211;300&#160;mOsm&#47;L&#41;&#46; La poliuria supone un reto diagn&#243;stico y su tratamiento correcto exige una evaluaci&#243;n de la historia cl&#237;nica&#44; la determinaci&#243;n de la osmolaridad urinaria&#44; la estimaci&#243;n del aclaramiento de agua libre&#44; el uso de pruebas de deprivaci&#243;n h&#237;drica en la poliuria acuosa y la medici&#243;n de electr&#243;litos en sangre y orina en el caso de la poliuria osm&#243;tica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ram&#237;rez-Guerrero G&#44; M&#252;ller-Ortiz H&#44; Pedreros-Rosales C&#46; Poliuria en el adulto&#46; Una aproximaci&#243;n diagn&#243;stica basada en la fisiopatolog&#237;a&#46; Rev Clin Esp&#46; 2022&#59;222&#58;301&#8211;308&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Suggested flowchart for the differential diagnosis of polyuria&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">UAG&#58; urine anion gap&#46; Difference in milliequivalents per liter between the sum of Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span> and Cl<span class="elsevierStyleInf">u</span>&#59; Ue&#58; urine electrolytes&#46; 2&#215; &#40;Na<span class="elsevierStyleInf">u</span>&#160;&#43;&#160;K<span class="elsevierStyleInf">u</span>&#41;&#46;</p>"
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        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Water deprivation test&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">In the figure&#44; it can be observed that the patient started the deprivation test with a reduced Osm<span class="elsevierStyleInf">u</span> and continued with diluted urine despite 240&#160;min of water deprivation&#46; Following administration of desmopressin&#44; a urine concentration appropriate for the Osm<span class="elsevierStyleInf">p</span> was achieved&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">DKA&#58; diabetic ketoacidosis&#59; iSGLT-2&#58; sodium&#47;glucose cotransporter 2 inhibitors&#59; ATN&#58; acute tubular necrosis&#59; HHS&#58; hyperglycemic hyperosmolar syndrome&#59; CNS&#58; central nervous system&#59; OU&#58; obstructive uropathy&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Osmotic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Electrolytes</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sodium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Infusion of iso- or hypertonic sodium chloride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal sodium losses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chloride&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diuretics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bartter syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bicarbonate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exogenous administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acetazolamide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ketoanion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DKA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Nonelectrolyte</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Glucose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exogenous loading&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DKA-HHS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">iSGLT-2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Urea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Exogenous loading&#44; protein or amino acids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypercatabolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ATN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">After OU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mannitol&#47;sorbitol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">Water</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Excess intake</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psychogenic polydipsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Iatrogenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Diabetes insipidus</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Central&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cranioencephalic trauma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNS tumors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNS infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sheehan syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Subarachnoid hemorrhage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNS lupus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sarcoidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nephrogenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypokalemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hypercalciuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lithium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sarcoidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sickle cell anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Obstructive uropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Polycystic kidney disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab2892436.png"
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        "descripcion" => array:1 [
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          "Quimica" => "Na<span class="elsevierStyleInf">u</span> 110&#160;mmol&#47;L&#160;&#215;&#160;6&#160;L&#160;&#61;&#160;660&#160;mmol"
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          "Quimica" => "Cl<span class="elsevierStyleInf">u</span> 149&#160;mmol&#47;L&#160;&#215;&#160;6&#160;L&#160;&#61;&#160;894&#160;mmol"
        ]
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:31 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polyuria-polydipsia syndrome&#58; a diagnostic challenge"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Nigro"
                            1 => "M&#46; Grossmann"
                            2 => "C&#46; Chiang"
                            3 => "W&#46; Inder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/imj.13627"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intern Med J&#46;"
                        "fecha" => "2018"
                        "volumen" => "48"
                        "paginaInicial" => "244"
                        "paginaFinal" => "253"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28967192"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tonicity balance in patients with hypernatremia acquired in the intensive care unit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Linder"
                            1 => "N&#46; Kneidinger"
                            2 => "U&#46; Holzinger"
                            3 => "W&#46; Druml"
                            4 => "C&#46; Schwarz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2009.04.015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis&#46;"
                        "fecha" => "2009"
                        "volumen" => "54"
                        "paginaInicial" => "674"
                        "paginaFinal" => "679"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19515476"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polyuria in relation to dysnatraemias in neurocritical care"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "V&#46; Spatenkova"
                            1 => "O&#46; Bradac"
                            2 => "P&#46; de Lacy"
                            3 => "P&#46; Skrabalek"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/02688697.2015.1054347"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Neurosurg&#46;"
                        "fecha" => "2015"
                        "volumen" => "29"
                        "paginaInicial" => "650"
                        "paginaFinal" => "654"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26402577"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Investigating polyuria"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Jakes"
                            1 => "S&#46; Bhandari"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "BMJ&#46;"
                        "fecha" => "2013"
                        "volumen" => "347"
                        "paginaInicial" => "6772"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The polyuria of solute diuresis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;R&#46; Oster"
                            1 => "I&#46; Singer"
                            2 => "L&#46; Thatte"
                            3 => "I&#46; Grant-Tylor"
                            4 => "J&#46;M&#46; Diego"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med&#46;"
                        "fecha" => "1997"
                        "volumen" => "157"
                        "paginaInicial" => "721"
                        "paginaFinal" => "729"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9125003"
                            "web" => "Medline"
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            5 => array:3 [
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              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Challenging consults&#58; application of principles of physiology and biochemistry to the bedside&#46; Osmotic diuresis&#58; the importance of counting the number of osmoles excreted"
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2021.03.003

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