Hyponatremia in refractory congestive heart failure patients treated with icodextrin-based peritoneal dialysis: A case series

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Holtzman, Dganit Dinour" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Margarita" "apellidos" => "Kunin" "email" => array:1 [ 0 => "Margarita.Kunin@sheba.health.gov.il" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Liat" "apellidos" => "Ganon" ] 2 => array:2 [ "nombre" => "Eli J." "apellidos" => "Holtzman" ] 3 => array:2 [ "nombre" => "Dganit" "apellidos" => "Dinour" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Nephrology and Hypertension Institute, Sheba Medical Center and Sackler Faculty of Medicine, Tel-Hashomer, Israel" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiponatremia en pacientes con insuficiencia cardíaca congestiva resistentes al tratamiento tratados con diálisis peritoneal con icodextrina: una serie de casos" ] ] "textoCompleto" => "IntroductionRemoval of extensive fluid overload is one of the most difficult challenges in the management of severe congestive heart failure (CHF), particularly in patients who do not respond to diuretic therapy. Peritoneal ultrafiltration (UF) is a simple choice for daily fluid removal. Today, peritoneal dialysis (PD) is increasingly used to treat hypervolemic CHF patients who are resistant to conventional therapies, in particular when complicated by renal insufficiency (reviewed in Refs. <a class="elsevierStyleCrossRefs" href="#bib0095">1, 2</a>). Icodextrin was proposed to be a good option for UF in refractory CHF patients.<a class="elsevierStyleCrossRefs" href="#bib0105">3–6</a> Icodextrin solution is a long-acting osmotic agent that allows the patient's UF volume to gradually increase for up to 12h.<a class="elsevierStyleCrossRefs" href="#bib0095">1,3</a> In a recently published systematic review<a class="elsevierStyleCrossRef" href="#bib0125">7</a> it was found that mortality in CHF patients treated with peritoneal UF was associated with less use of icodextrin.Icodextrin is generally well tolerated. A small, although statistically significant reduction in serum sodium (∼2mmol/l) consistently observed in multiple trials, is likely not clinically relevant.<a class="elsevierStyleCrossRef" href="#bib0130">8</a> Two female diabetic patients treated by icodextrin-based PD developed severe hyponatraemia with plasma Na<121mmol/l and neurological complications.<a class="elsevierStyleCrossRef" href="#bib0135">9</a> The mechanism by which icodextrin causes hyponatremia is unclear. It was proposed that icodextrin solution leads to accumulation of maltose in the extracellular volume and this gradient induces osmotic flow by a mechanism similar to isosmolar colloid osmosis. The resultant shift in water from the intracellular to the extracellular space can result in dilutional hyponatremia.<a class="elsevierStyleCrossRef" href="#bib0130">8</a> It was demonstrated that icodextrin increased peritoneal Na removal.<a class="elsevierStyleCrossRef" href="#bib0140">10</a>Five refractory CHF patients treated with peritoneal ultrafiltration in our unit, developed significant symptomatic hyponatremia with Na<130mmol/l after icodextrin was added to their program (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Cases descriptionPatient 1A 63-year-old woman with history of diabetes mellitus (DM), restrictive cardiomyopathy and severe pulmonary hypertension was referred to PD due to significant volume overload. Her eGFR was 27ml/min/1.73m2. She had no proteinuria and renal sonography showed small kidneys. Her kidney disease was attributed to nephrosclerosis with cardiorenal component. She was treated with one dianeal glucose solution 4.25% exchange per day for 6 weeks, then icodextrin was added to her program. She continued the treatment with furosemide and was on sodium restriction diet. Her urinary sodium at icodextrin start was 78meq/l. Following icodextrin start a serum sodium dropped from 136.3 to 128.3meq/l (average of 3 consecutive values) with the lowest value measured of 126meq/l. The patient complained of extreme weakness and fatigue. Icodextrin was stopped and dianeal glucose solution 2.5% was started. After icodextrin stop serum sodium raised to 134.7meq/l (average of 3 consecutive values). Due to difficulty to maintain adequate ultrafiltration and worsening diabetes mellitus control, icodextrin was restarted. Serum sodium dropped to 128.7meq/l (average of 3 consecutive values), lowest value measured was 128meq/l. The patient complained of extreme weakness and fatigue, therefore icodextrin was stopped again. A month later average serum sodium was 133meq/l. The patient died a month later from heart failure exacerbation.Patient 2A 64-year-old woman with hypertrophic cardiomyopathy was referred to PD due to significant volume overload. She had no proteinuria and demonstrated normal kidneys in renal sonography. Her kidney disease was attributed to cardiorenal syndrome. At PD start the patient's eGFR was 23ml/min/1.73m2. From the very beginning she turned to be hypotensive and oliguric. The patient was 8 months on PD with 3 glucose 2.5% exchanges per day. Furosemide was stopped due to oliguria and hypotension. Urinary sodium was 49meq/l and the patient continued to be edematous. After icodextrin addition serum sodium dropped from 133.7 to 126.3meq/l (average of 3 consecutive values) with the lowest value measured of 125meq/l. The patient continued with icodextrin despite low serum sodium. Non-adherence to free water restriction was suspected. Despite the attempts to restrict free water consumption by the patient serum sodium remained low. The patient died 5 months later from septic shock due to infected cardiac pacemaker electrode.Patient 3An 82-year-old man with ischemic cardiomyopathy and low LVEF started PD due to resistant volume overload. At the admission his eGFR was 26ml/min/1.73m2. He had non-nephrotic proteinuria and reduced parenchyma size in kidney sonography. His renal disease was attributed to nephrosclerosis with cardiorenal component. He was treated with PD for one month with 2 exchanges per day: glucose 2.5% and glucose 4.25%. He continued treatment with furosemide and was on sodium restriction diet. His urinary sodium was 53meq/l. After icodextrin addition serum sodium dropped from 134.7 to 129.3meq/l (average of 3 consecutive values) with the lowest value measured of 127meq/l. The patient continued with icodextrin despite low serum sodium. He was diagnosed with hip fracture without the history of trauma or fall. He did not recover from the surgery and eventually died in the hospital.Patient 4A 75-year-old woman with severe primary pulmonary hypertension and cardiorenal syndrome started PD due to resistant volume overload. At the admission her eGFR was 36ml/min/1.73m2. The patient was treated with one glucose 4.25% exchange per day for 2 months. She was edematous therefore icodextrin was added. She continued treatment with furosemide and was on sodium restriction diet. Her urinary sodium was 26meq/l. After icodextrin start serum sodium dropped from 137.3 to 129meq/l (average of 3 consecutive values) with the lowest value measured of 128meq/l. She was reported by her family to be confused. She fell down and broke her hip neck. Icodextrin was stopped during the hospitalization. A month later average serum sodium was 138meq/l (average of 3 consecutive values). The patient eventually died from complications of orthopedic surgery.Patient 5An 85-year-old man with ischemic cardiomyopathy, low LVEF, severe pulmonary hypertension and diabetes mellitus started with peritoneal UF due to refractory volume overload. His eGFR was 43ml/min/1.73m2 at PD start. He had no proteinuria and normal kidneys in sonography. His kidney disease was attributed to cardiorenal syndrome. He was treated with one glucose 4.25% exchange per day for 3 month, then icodextrin was added. He continued treatment with furosemide and was on sodium restriction diet. His urinary sodium was 31meq/l. After icodextrin start serum sodium dropped from 138.3 to 130meq/l (average of 3 consecutive values) with the lowest value measured of 127meq/l. Icodextrin was stopped. A month later serum sodium was 138.6meq/l (average of 3 consecutive values).Comparison of severe hyponatremia group with mild hyponatremia groupTo find out which patients were more susceptible to severe hyponatremia after icodextrin addition we compared the characteristics of the above 5 patients as a group (median serum sodium was 129meq/l, range 126.3–130meq/l) with the data of 12 refractory CHF patients who were treated with icodextrin during the same period but their median serum sodium was 134.5meq/l (range 132.3–136.7meq/l). Higher SPAP was more likely connected to significant hyponatremia: median SPAP measured 78mmHg (range 43–92mmHg) in severe hyponatremia group compared to 49mmHg (range 37–67mmHg) in mild hyponatremia group (p=0.0225). Patients who developed significant hyponatremia died earlier compared to patients with insignificant hyponatremia. Median survival was 5 months (range 2–7 months) in severe hyponatremia group compared to 15.5 months (range 6–50 months) in mild hyponatremia group (p=0.0318). There was a tendency for significant sodium drop in women compared to men: in significant hyponatremia group 60% were women compared to 8% women in mild hyponatremia group (p=0.0525). Patients with lower baseline sodium showed a tendency for a more significant sodium drop compared to those with higher baseline sodium. Baseline serum sodium was 136.3meq/l (range 133.7–137.3meq/l) in the severe hyponatremia group compared to 138meq/l (range 134.3–141meq/l) in mild hyponatremia group (p=0.0854).There was no difference between the groups in NYHA functional class, diabetes mellitus rate, serum creatinine and albumin levels, baseline urinary sodium or diuretics use.DiscussionWe presented the group of patients who developed clinically relevant hyponatremia following icodextrin addition to the program. Five refractory CHF patients showed serum sodium drop by median of 8meq/l during the first month of icodextrin treatment, more profound decrease than previously reported (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0145">11–13</a>It have been proposed that several mechanisms could explain the development of hyponatremia in PD, including net water gain due to excessive water intake or low ultrafiltration rate of free-water, negative Na+/K+ balance caused by low Na+/K+ intake or high Na+/K+ removal, and shift of intracellular water to extracellular space induced by the use of icodextrin or hypercatabolism and malnutrition.<a class="elsevierStyleCrossRef" href="#bib0160">14</a>CHF patients had a tendency to low serum sodium level due to neurohumoral activation. The neurohumoral changes limit both sodium and water excretion in an attempt to return perfusion pressure to normal. ADH release directly enhances water reabsorption in the collecting tubules, whereas angiotensin II and norepinephrine limit distal water delivery by reduction in renal perfusion and by increasing proximal sodium and water reabsorption.<a class="elsevierStyleCrossRef" href="#bib0165">15</a> In addition, both the low cardiac output and high angiotensin II levels are potent stimuli to thirst, leading to enhanced water intake. While significant hyponatremia was temporarily related to icodextrin start, we could not exclude the possibility that hyponatremia in these patients is multifactorial. Probably some our patients were non-adherent to free water restriction, while others demonstrated hyperglycemia (although corrected serum sodium was also low). Other possible contributors to hyponatremia in those patients are dietary restriction and chronic use of diuretics. The risk factors for hyponatremia were female sex, low initial sodium level and increased SPAP. All patients except one had hypertonic glucose 4.25% in their program which could increase thirst and as a result free water consumption. Perhaps, icodextrin metabolites accumulation rises serum osmolality, stimulates thirst and free water consumption which further contribute to hyponatremia in those severe CHF patients.In our cases patients with severe hyponatremia had lower survival compared to mild hyponatremia group. The studies demonstrated that severe underlying disease worsens hyponatremia and clinical outcome.<a class="elsevierStyleCrossRef" href="#bib0160">14</a> Hyponatremia itself may be a surrogate marker for the severity of underlying disease.<a class="elsevierStyleCrossRef" href="#bib0160">14</a> Hyponatremia is known to be an important marker and prognostic factor of left-sided heart failure.<a class="elsevierStyleCrossRef" href="#bib0170">16</a> Recently, it was demonstrated that hyponatremia was an indicator of poor prognosis in patients with echocardiographic evidence of pulmonary hypertension and preserved left ventricular systolic function.<a class="elsevierStyleCrossRef" href="#bib0175">17</a> Perhaps, patients with certain heart failure etiologies and severe heart disease (as represented by lower survival rate compared to mild hyponatremia group) are more susceptible to this complication.Two CHF patients who developed significant hyponatremia following icodextrin treatment suffered from hip fracture. There is an emerging literature that suggests that hyponatremia increases the adjusted odds ratio for both falls and fractures in the elderly.<a class="elsevierStyleCrossRef" href="#bib0180">18</a> Hyponatremia appears to contribute to falls and fractures by two mechanisms: it produces mild cognitive impairment resulting in unsteady gait and falls and it directly contributes to bone impairment through osteoporosis due to increased bone resorption in order to mobilize sodium from the bone or altered bone quality through decreased bone microfracture repair.<a class="elsevierStyleCrossRef" href="#bib0180">18</a>ConclusionsHyponatremia in refractory CHF patients is multifactorial. In rare cases, icodextrin may contribute to clinically relevant hyponatremia if the hyponatremia is compounded by other factors. Severe hyponatremia in icodextrin users was associated with poorer survival and is most likely a marker of advanced heart disease. This could be a signal to physician to consider alternative and probably more aggressive interventions.Conflict of interestsThe authors declare they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres985617" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec953266" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres985616" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec953265" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Cases description" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient 2" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Patient 3" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Patient 4" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Patient 5" ] ] ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Comparison of severe hyponatremia group with mild hyponatremia group" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-11-21" "fechaAceptado" => "2017-05-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec953266" "palabras" => array:3 [ 0 => "Hyponatremia" 1 => "Congestive heart failure" 2 => "Peritoneal dialysis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec953265" "palabras" => array:3 [ 0 => "Hiponatremia" 1 => "Insuficiencia cardíaca congestiva" 2 => "Diálisis peritoneal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Severe congestive heart failure (CHF) patients are prone to hyponatremia. Peritoneal dialysis (PD) is increasingly used for long-term management of refractory CHF patients. The glucose polymer icodextrin was proposed to be a good option for fluid removal in such patients. A small, although statistically significant reduction in serum sodium (∼2mmol/l) consistently observed in multiple trials, is considered as not clinically relevant. Here we reported five refractory CHF patients who demonstrated sodium drop by median of 8meq/l (range 5.4–8.3meq/l) after icodextrin was added to their program. It seems that icodextrin may contribute to clinically relevant hyponatremia if the hyponatremia is compounded by other factors. Patients with extremely severe congestive heart failure are susceptible to this complication." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Los pacientes con insuficiencia cardíaca congestiva grave son propensos a sufrir hiponatremia. La diálisis peritoneal se utiliza cada vez más para el tratamiento a largo plazo de los pacientes con insuficiencia cardíaca congestiva resistentes al tratamiento. El polímero de glucosa icodextrina se propuso como una buena opción para la ultrafiltración. Una reducción pequeña, aunque estadísticamente significativa, del sodio sérico (∼2mmol/l) observada sistemáticamente en numerosos ensayos no se considera de relevancia clínica. En este documento informamos de 5 casos de pacientes con insuficiencia cardíaca congestiva resistentes al tratamiento que presentaron una caída de las concentraciones de sodio en una mediana de 8mEq/l (intervalo 5,4-8,3mEq/l) después de la adición de icodextrina a su programa. Parece ser que la icodextrina puede contribuir a una hiponatremia clínicamente relevante si se combina con otros factores. Los pacientes con insuficiencia cardíaca congestiva muy grave son propensos a esta complicación." ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 5 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">f \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">f \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">m \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">f \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">m \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology of heart disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Restrictive cardiomyopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypertrophic cardiomyopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ischemic cardiomyopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Primary pulmonary hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ischemic cardiomyopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology of renal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nephrosclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cardiorenal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nephrosclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cardiorenal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cardiorenal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum sodium (meq/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">136.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">133.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">134.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">137.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">138.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum sodium (meq/l) 1 month after icodextrin start \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">128.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">126.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">129.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">129 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum glucose (mg/dL) 1 month after icodextrin start \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">114.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">192.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">118.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">232.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum albumin (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Estimated SPAP (mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diuretics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Furosemide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Furosemide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Furosemide \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Furosemide \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other solutions (L/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.25% – 2L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5% - 6L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.25% – 2L 2.5% – 2L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.25% – 2L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.25% – 2L \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clinical symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Restlessness, muscle weakness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Confusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Confusion, hip fracture  \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Confusion, hip fracture \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Weakness, fatigue \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1672143.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Cases of severe hyponatremia following icodextrin treatment." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0095" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Peritoneal dialysis for chronic congestive heart failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. 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Case report

Hiponatremia en pacientes con insuficiencia cardíaca congestiva resistentes al tratamiento tratados con diálisis peritoneal con icodextrina: una serie de casos

Margarita Kunin

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Margarita.Kunin@sheba.health.gov.il

Corresponding author.

, Liat Ganon, Eli J. Holtzman, Dganit Dinour

Nephrology and Hypertension Institute, Sheba Medical Center and Sackler Faculty of Medicine, Tel-Hashomer, Israel

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    "titulo" => "Hyponatremia in refractory congestive heart failure patients treated with icodextrin-based peritoneal dialysis&#58; A case series"
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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">Removal of extensive fluid overload is one of the most difficult challenges in the management of severe congestive heart failure &#40;CHF&#41;&#44; particularly in patients who do not respond to diuretic therapy&#46; Peritoneal ultrafiltration &#40;UF&#41; is a simple choice for daily fluid removal&#46; Today&#44; peritoneal dialysis &#40;PD&#41; is increasingly used to treat hypervolemic CHF patients who are resistant to conventional therapies&#44; in particular when complicated by renal insufficiency &#40;reviewed in Refs&#46; <a class="elsevierStyleCrossRefs" href="#bib0095">1&#44; 2</a>&#41;&#46; Icodextrin was proposed to be a good option for UF in refractory CHF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">3&#8211;6</span></a> Icodextrin solution is a long-acting osmotic agent that allows the patient&#39;s UF volume to gradually increase for up to 12<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">1&#44;3</span></a> In a recently published systematic review<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">7</span></a> it was found that mortality in CHF patients treated with peritoneal UF was associated with less use of icodextrin&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Icodextrin is generally well tolerated&#46; A small&#44; although statistically significant reduction in serum sodium &#40;&#8764;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; consistently observed in multiple trials&#44; is likely not clinically relevant&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> Two female diabetic patients treated by icodextrin-based PD developed severe hyponatraemia with plasma Na<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>121<span class="elsevierStyleHsp" style=""></span>mmol&#47;l and neurological complications&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">9</span></a> The mechanism by which icodextrin causes hyponatremia is unclear&#46; It was proposed that icodextrin solution leads to accumulation of maltose in the extracellular volume and this gradient induces osmotic flow by a mechanism similar to isosmolar colloid osmosis&#46; The resultant shift in water from the intracellular to the extracellular space can result in dilutional hyponatremia&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">8</span></a> It was demonstrated that icodextrin increased peritoneal Na removal&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Five refractory CHF patients treated with peritoneal ultrafiltration in our unit&#44; developed significant symptomatic hyponatremia with Na<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>130<span class="elsevierStyleHsp" style=""></span>mmol&#47;l after icodextrin was added to their program &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Cases description</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Patient 1</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 63-year-old woman with history of diabetes mellitus &#40;DM&#41;&#44; restrictive cardiomyopathy and severe pulmonary hypertension was referred to PD due to significant volume overload&#46; Her eGFR was 27<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; She had no proteinuria and renal sonography showed small kidneys&#46; Her kidney disease was attributed to nephrosclerosis with cardiorenal component&#46; She was treated with one dianeal glucose solution 4&#46;25&#37; exchange per day for 6 weeks&#44; then icodextrin was added to her program&#46; She continued the treatment with furosemide and was on sodium restriction diet&#46; Her urinary sodium at icodextrin start was 78<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; Following icodextrin start a serum sodium dropped from 136&#46;3 to 128&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41; with the lowest value measured of 126<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; The patient complained of extreme weakness and fatigue&#46; Icodextrin was stopped and dianeal glucose solution 2&#46;5&#37; was started&#46; After icodextrin stop serum sodium raised to 134&#46;7<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41;&#46; Due to difficulty to maintain adequate ultrafiltration and worsening diabetes mellitus control&#44; icodextrin was restarted&#46; Serum sodium dropped to 128&#46;7<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41;&#44; lowest value measured was 128<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; The patient complained of extreme weakness and fatigue&#44; therefore icodextrin was stopped again&#46; A month later average serum sodium was 133<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; The patient died a month later from heart failure exacerbation&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patient 2</span><p id="par0025" class="elsevierStylePara elsevierViewall">A 64-year-old woman with hypertrophic cardiomyopathy was referred to PD due to significant volume overload&#46; She had no proteinuria and demonstrated normal kidneys in renal sonography&#46; Her kidney disease was attributed to cardiorenal syndrome&#46; At PD start the patient&#39;s eGFR was 23<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; From the very beginning she turned to be hypotensive and oliguric&#46; The patient was 8 months on PD with 3 glucose 2&#46;5&#37; exchanges per day&#46; Furosemide was stopped due to oliguria and hypotension&#46; Urinary sodium was 49<span class="elsevierStyleHsp" style=""></span>meq&#47;l and the patient continued to be edematous&#46; After icodextrin addition serum sodium dropped from 133&#46;7 to 126&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41; with the lowest value measured of 125<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; The patient continued with icodextrin despite low serum sodium&#46; Non-adherence to free water restriction was suspected&#46; Despite the attempts to restrict free water consumption by the patient serum sodium remained low&#46; The patient died 5 months later from septic shock due to infected cardiac pacemaker electrode&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Patient 3</span><p id="par0030" class="elsevierStylePara elsevierViewall">An 82-year-old man with ischemic cardiomyopathy and low LVEF started PD due to resistant volume overload&#46; At the admission his eGFR was 26<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; He had non-nephrotic proteinuria and reduced parenchyma size in kidney sonography&#46; His renal disease was attributed to nephrosclerosis with cardiorenal component&#46; He was treated with PD for one month with 2 exchanges per day&#58; glucose 2&#46;5&#37; and glucose 4&#46;25&#37;&#46; He continued treatment with furosemide and was on sodium restriction diet&#46; His urinary sodium was 53<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; After icodextrin addition serum sodium dropped from 134&#46;7 to 129&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41; with the lowest value measured of 127<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; The patient continued with icodextrin despite low serum sodium&#46; He was diagnosed with hip fracture without the history of trauma or fall&#46; He did not recover from the surgery and eventually died in the hospital&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Patient 4</span><p id="par0035" class="elsevierStylePara elsevierViewall">A 75-year-old woman with severe primary pulmonary hypertension and cardiorenal syndrome started PD due to resistant volume overload&#46; At the admission her eGFR was 36<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46; The patient was treated with one glucose 4&#46;25&#37; exchange per day for 2 months&#46; She was edematous therefore icodextrin was added&#46; She continued treatment with furosemide and was on sodium restriction diet&#46; Her urinary sodium was 26<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; After icodextrin start serum sodium dropped from 137&#46;3 to 129<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41; with the lowest value measured of 128<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; She was reported by her family to be confused&#46; She fell down and broke her hip neck&#46; Icodextrin was stopped during the hospitalization&#46; A month later average serum sodium was 138<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41;&#46; The patient eventually died from complications of orthopedic surgery&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Patient 5</span><p id="par0040" class="elsevierStylePara elsevierViewall">An 85-year-old man with ischemic cardiomyopathy&#44; low LVEF&#44; severe pulmonary hypertension and diabetes mellitus started with peritoneal UF due to refractory volume overload&#46; His eGFR was 43<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> at PD start&#46; He had no proteinuria and normal kidneys in sonography&#46; His kidney disease was attributed to cardiorenal syndrome&#46; He was treated with one glucose 4&#46;25&#37; exchange per day for 3 month&#44; then icodextrin was added&#46; He continued treatment with furosemide and was on sodium restriction diet&#46; His urinary sodium was 31<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; After icodextrin start serum sodium dropped from 138&#46;3 to 130<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41; with the lowest value measured of 127<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#46; Icodextrin was stopped&#46; A month later serum sodium was 138&#46;6<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;average of 3 consecutive values&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Comparison of severe hyponatremia group with mild hyponatremia group</span><p id="par0045" class="elsevierStylePara elsevierViewall">To find out which patients were more susceptible to severe hyponatremia after icodextrin addition we compared the characteristics of the above 5 patients as a group &#40;median serum sodium was 129<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#44; range 126&#46;3&#8211;130<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#41; with the data of 12 refractory CHF patients who were treated with icodextrin during the same period but their median serum sodium was 134&#46;5<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;range 132&#46;3&#8211;136&#46;7<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#41;&#46; Higher SPAP was more likely connected to significant hyponatremia&#58; median SPAP measured 78<span class="elsevierStyleHsp" style=""></span>mmHg &#40;range 43&#8211;92<span class="elsevierStyleHsp" style=""></span>mmHg&#41; in severe hyponatremia group compared to 49<span class="elsevierStyleHsp" style=""></span>mmHg &#40;range 37&#8211;67<span class="elsevierStyleHsp" style=""></span>mmHg&#41; in mild hyponatremia group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0225&#41;&#46; Patients who developed significant hyponatremia died earlier compared to patients with insignificant hyponatremia&#46; Median survival was 5 months &#40;range 2&#8211;7 months&#41; in severe hyponatremia group compared to 15&#46;5 months &#40;range 6&#8211;50 months&#41; in mild hyponatremia group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0318&#41;&#46; There was a tendency for significant sodium drop in women compared to men&#58; in significant hyponatremia group 60&#37; were women compared to 8&#37; women in mild hyponatremia group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0525&#41;&#46; Patients with lower baseline sodium showed a tendency for a more significant sodium drop compared to those with higher baseline sodium&#46; Baseline serum sodium was 136&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;range 133&#46;7&#8211;137&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#41; in the severe hyponatremia group compared to 138<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;range 134&#46;3&#8211;141<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#41; in mild hyponatremia group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0854&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">There was no difference between the groups in NYHA functional class&#44; diabetes mellitus rate&#44; serum creatinine and albumin levels&#44; baseline urinary sodium or diuretics use&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">We presented the group of patients who developed clinically relevant hyponatremia following icodextrin addition to the program&#46; Five refractory CHF patients showed serum sodium drop by median of 8<span class="elsevierStyleHsp" style=""></span>meq&#47;l during the first month of icodextrin treatment&#44; more profound decrease than previously reported &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">It have been proposed that several mechanisms could explain the development of hyponatremia in PD&#44; including net water gain due to excessive water intake or low ultrafiltration rate of free-water&#44; negative Na&#43;&#47;K&#43; balance caused by low Na&#43;&#47;K&#43; intake or high Na&#43;&#47;K&#43; removal&#44; and shift of intracellular water to extracellular space induced by the use of icodextrin or hypercatabolism and malnutrition&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">CHF patients had a tendency to low serum sodium level due to neurohumoral activation&#46; The neurohumoral changes limit both sodium and water excretion in an attempt to return perfusion pressure to normal&#46; ADH release directly enhances water reabsorption in the collecting tubules&#44; whereas angiotensin II and norepinephrine limit distal water delivery by reduction in renal perfusion and by increasing proximal sodium and water reabsorption&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">15</span></a> In addition&#44; both the low cardiac output and high angiotensin II levels are potent stimuli to thirst&#44; leading to enhanced water intake&#46; While significant hyponatremia was temporarily related to icodextrin start&#44; we could not exclude the possibility that hyponatremia in these patients is multifactorial&#46; Probably some our patients were non-adherent to free water restriction&#44; while others demonstrated hyperglycemia &#40;although corrected serum sodium was also low&#41;&#46; Other possible contributors to hyponatremia in those patients are dietary restriction and chronic use of diuretics&#46; The risk factors for hyponatremia were female sex&#44; low initial sodium level and increased SPAP&#46; All patients except one had hypertonic glucose 4&#46;25&#37; in their program which could increase thirst and as a result free water consumption&#46; Perhaps&#44; icodextrin metabolites accumulation rises serum osmolality&#44; stimulates thirst and free water consumption which further contribute to hyponatremia in those severe CHF patients&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In our cases patients with severe hyponatremia had lower survival compared to mild hyponatremia group&#46; The studies demonstrated that severe underlying disease worsens hyponatremia and clinical outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> Hyponatremia itself may be a surrogate marker for the severity of underlying disease&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">14</span></a> Hyponatremia is known to be an important marker and prognostic factor of left-sided heart failure&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> Recently&#44; it was demonstrated that hyponatremia was an indicator of poor prognosis in patients with echocardiographic evidence of pulmonary hypertension and preserved left ventricular systolic function&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> Perhaps&#44; patients with certain heart failure etiologies and severe heart disease &#40;as represented by lower survival rate compared to mild hyponatremia group&#41; are more susceptible to this complication&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Two CHF patients who developed significant hyponatremia following icodextrin treatment suffered from hip fracture&#46; There is an emerging literature that suggests that hyponatremia increases the adjusted odds ratio for both falls and fractures in the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a> Hyponatremia appears to contribute to falls and fractures by two mechanisms&#58; it produces mild cognitive impairment resulting in unsteady gait and falls and it directly contributes to bone impairment through osteoporosis due to increased bone resorption in order to mobilize sodium from the bone or altered bone quality through decreased bone microfracture repair&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusions</span><p id="par0080" class="elsevierStylePara elsevierViewall">Hyponatremia in refractory CHF patients is multifactorial&#46; In rare cases&#44; icodextrin may contribute to clinically relevant hyponatremia if the hyponatremia is compounded by other factors&#46; Severe hyponatremia in icodextrin users was associated with poorer survival and is most likely a marker of advanced heart disease&#46; This could be a signal to physician to consider alternative and probably more aggressive interventions&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interests</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare they have no conflict of interest&#46;</p></span></span>"
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          "identificador" => "xpalclavsec953265"
          "titulo" => "Palabras clave"
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        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Cases description"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patient 1"
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            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Patient 2"
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            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Patient 3"
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            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Patient 4"
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            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Patient 5"
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        6 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Comparison of severe hyponatremia group with mild hyponatremia group"
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        7 => array:2 [
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          "titulo" => "Discussion"
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          "titulo" => "Conclusions"
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          "identificador" => "sec0055"
          "titulo" => "Conflict of interests"
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        10 => array:1 [
          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-11-21"
    "fechaAceptado" => "2017-05-02"
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          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec953266"
          "palabras" => array:3 [
            0 => "Hyponatremia"
            1 => "Congestive heart failure"
            2 => "Peritoneal dialysis"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec953265"
          "palabras" => array:3 [
            0 => "Hiponatremia"
            1 => "Insuficiencia card&#237;aca congestiva"
            2 => "Di&#225;lisis peritoneal"
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Severe congestive heart failure &#40;CHF&#41; patients are prone to hyponatremia&#46; Peritoneal dialysis &#40;PD&#41; is increasingly used for long-term management of refractory CHF patients&#46; The glucose polymer icodextrin was proposed to be a good option for fluid removal in such patients&#46; A small&#44; although statistically significant reduction in serum sodium &#40;&#8764;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; consistently observed in multiple trials&#44; is considered as not clinically relevant&#46; Here we reported five refractory CHF patients who demonstrated sodium drop by median of 8<span class="elsevierStyleHsp" style=""></span>meq&#47;l &#40;range 5&#46;4&#8211;8&#46;3<span class="elsevierStyleHsp" style=""></span>meq&#47;l&#41; after icodextrin was added to their program&#46; It seems that icodextrin may contribute to clinically relevant hyponatremia if the hyponatremia is compounded by other factors&#46; Patients with extremely severe congestive heart failure are susceptible to this complication&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con insuficiencia card&#237;aca congestiva grave son propensos a sufrir hiponatremia&#46; La di&#225;lisis peritoneal se utiliza cada vez m&#225;s para el tratamiento a largo plazo de los pacientes con insuficiencia card&#237;aca congestiva resistentes al tratamiento&#46; El pol&#237;mero de glucosa icodextrina se propuso como una buena opci&#243;n para la ultrafiltraci&#243;n&#46; Una reducci&#243;n peque&#241;a&#44; aunque estad&#237;sticamente significativa&#44; del sodio s&#233;rico &#40;&#8764;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;l&#41; observada sistem&#225;ticamente en numerosos ensayos no se considera de relevancia cl&#237;nica&#46; En este documento informamos de 5 casos de pacientes con insuficiencia card&#237;aca congestiva resistentes al tratamiento que presentaron una ca&#237;da de las concentraciones de sodio en una mediana de 8<span class="elsevierStyleHsp" style=""></span>mEq&#47;l &#40;intervalo 5&#44;4-8&#44;3<span class="elsevierStyleHsp" style=""></span>mEq&#47;l&#41; despu&#233;s de la adici&#243;n de icodextrina a su programa&#46; Parece ser que la icodextrina puede contribuir a una hiponatremia cl&#237;nicamente relevante si se combina con otros factores&#46; Los pacientes con insuficiencia card&#237;aca congestiva muy grave son propensos a esta complicaci&#243;n&#46;</p></span>"
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                  <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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Case 5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">f&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">f&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">f&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">m&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology of heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Restrictive cardiomyopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypertrophic cardiomyopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ischemic cardiomyopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Primary pulmonary hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ischemic cardiomyopathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Etiology of renal disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nephrosclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cardiorenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Nephrosclerosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cardiorenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cardiorenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum sodium &#40;meq&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">136&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">133&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">134&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">137&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">138&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum sodium &#40;meq&#47;l&#41; 1 month after icodextrin start&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">128&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">126&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">129&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">129&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum glucose &#40;mg&#47;dL&#41; 1 month after icodextrin start&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">114&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">192&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">232&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum creatinine &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum albumin &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LVEF &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Estimated SPAP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">56&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diuretics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Furosemide&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Furosemide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Furosemide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Furosemide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other solutions &#40;L&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;25&#37; &#8211; 2<span class="elsevierStyleHsp" style=""></span>L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5&#37; - 6<span class="elsevierStyleHsp" style=""></span>L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;25&#37; &#8211; 2<span class="elsevierStyleHsp" style=""></span>L<br>2&#46;5&#37; &#8211; 2<span class="elsevierStyleHsp" style=""></span>L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;25&#37; &#8211; 2<span class="elsevierStyleHsp" style=""></span>L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;25&#37; &#8211; 2<span class="elsevierStyleHsp" style=""></span>L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clinical symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Restlessness&#44; muscle weakness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Confusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Confusion&#44;<br>hip fracture<br>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Confusion&#44; hip fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Weakness&#44; fatigue&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2017.05.017

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	6	13
2024 October	102	41	143
2024 September	76	26	102
2024 August	81	66	147
2024 July	47	25	72
2024 June	78	29	107
2024 May	75	42	117
2024 April	66	36	102
2024 March	39	22	61
2024 February	43	36	79
2024 January	46	25	71
2023 December	53	25	78
2023 November	68	34	102
2023 October	81	39	120
2023 September	70	23	93
2023 August	59	31	90
2023 July	80	33	113
2023 June	54	26	80
2023 May	92	34	126
2023 April	60	38	98
2023 March	73	25	98
2023 February	62	12	74
2023 January	48	31	79
2022 December	84	44	128
2022 November	85	40	125
2022 October	87	80	167
2022 September	63	45	108
2022 August	74	58	132
2022 July	83	49	132
2022 June	60	52	112
2022 May	98	29	127
2022 April	122	50	172
2022 March	66	47	113
2022 February	76	51	127
2022 January	62	46	108
2021 December	95	42	137
2021 November	75	29	104
2021 October	85	65	150
2021 September	46	36	82
2021 August	56	34	90
2021 July	57	38	95
2021 June	49	28	77
2021 May	45	54	99
2021 April	101	88	189
2021 March	73	34	107
2021 February	69	38	107
2021 January	48	28	76
2020 December	38	16	54
2020 November	35	17	52
2020 October	34	17	51
2020 September	50	24	74
2020 August	46	20	66
2020 July	52	15	67
2020 June	35	30	65
2020 May	38	19	57
2020 April	58	19	77
2020 March	38	18	56
2020 February	39	18	57
2020 January	53	21	74
2019 December	32	28	60
2019 November	53	39	92
2019 October	34	22	56
2019 September	39	20	59
2019 August	163	24	187
2019 July	49	18	67
2019 June	37	27	64
2019 May	43	30	73
2019 April	94	36	130
2019 March	57	32	89
2019 February	35	21	56
2019 January	39	27	66
2018 December	67	34	101
2018 November	63	17	80
2018 October	39	7	46
2018 September	42	14	56
2018 August	33	8	41
2018 July	38	17	55
2018 June	38	15	53
2018 May	44	11	55
2018 April	44	16	60
2018 March	52	14	66
2018 February	39	5	44

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