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Background: Chronic hyponatremia is known to be associated with osteoporosis. It has been shown that chronic hyponatremia increases bone resorption in an attempt to release body stores of exchangeable sodium by different mechanisms. We wanted to know the calciuria of patients with hyponatremia of different origins. Material and Methods: We made a retrospective study of 114 consecutive patients with asymptomatic hyponatremia of different origins with the usual serum and urine chemistry. Result: In hyponatremia due to SIADH, we had a high urine calcium/creatinine ratio of 0.23 ± 0.096 while in patients with salt depletion the UCa/UCr ratio was low (0.056 ± 0.038), in patients with hyponatremia secondary to thiazide intake the value was also low (0.075 ± 0.047) as in hypervolemic patients (0.034 ± 0.01). In hyponatremia due to polydipsia, the value was high (0.205 ± 0.10). Correction of hyponatremia in the euvolemic patients was associated with a significant decrease in the UCa/UCr ratio. In patients with hyponatremia secondary to thiazide intake, we noted that in the patients with low uric acid levels (0.15). This is also observed in hyponatremia secondary to polydipsia. Patients with thiazide-induced hyponatremia usually have low UCa/UCr levels and this is the case even among those with a biochemistry similar to that in SIADH (uric acid < 4 mg/dL).

Background: We previously reported that for around 5% of patients hospitalized with hyponatremia, it was related to what is called “transient renal salt wasting” (TRSW). In the present study we ask whether TRSW can also be observed in patients without hyponatremia. Methods: In this observational retrospective study we analyze the urine solute excretion of 200 consecutive normonatremic patients with normal kidney function and admitted in our department over one year. Patients were selected for analyses of FE.K, UCa/UCr and FE.PO4 if FE.Na was higher than 2% (N < 1.6%) before any treatment, and only if they were not taking diuretics. Result: Eleven normonatremic patients presented with transient high FE.Na > 2% on admission (2.9 ± 0.6% with a high FE.K of 28 ± 6.4%; a high UCa/UCr of 0.37 ± 0.13 and a high FE.PO4 of 23.2 ± 9.6%). All of these patients were elderly. Seven were female and four were male. Neurological disorders were observed in six patients (three strokes, one transient ischemic attack, one syncope and one epileptic attack). Heart problems were observed in three patients (all angina pectoris, two of which also had HBP). One patient presented with rectal bleeding with HBP, and another presented COPD with a pneumothorax. One patient with angina pectoris showed a transient relapse after four days of hospitalization (FE.Na 3.6%). The urine electrolyte excretion in these patients are similar to those observed after furosemide intake. Conclusion: Normonatremic TRSW is not a rare observation, particularly in patients with neurological or cardiac problems.

This article will discuss the consequences of chronic hyponatremia. In conditions such as cancer, heart failure, liver cirrhosis, or chronic kidney disease, the presence and magnitude of hypotonic hyponatremia are considered to reflect the severity of the underlying disease and are associated with increased morbidity as well as mortality. Hyponatremia can be acute (2–3 days). Chronic hyponatremia is associated with attention deficit, dizziness, tiredness, gait disturbance, falls, sarcopenia, bone fractures, osteoporosis, hypercalciuria (in the syndrome of inappropriate antidiuresis—SIADH), and kidney stones. In vitro studies have shown that cells grown in a low concentration of extracellular sodium have a greater proliferation rate and motility. Patients with chronic hyponatremia are more likely to develop cancer. We will not review the clinical consequences of respiratory arrest and osmotic demyelination syndrome (ODS) of the too-late or excessive treatment of hyponatremia.

We aimed to study the effects of daily variation in solute intake on urine volume in patients with syndrome of inappropriate secretion of antidiuretic hormone secretion (SIADH), syndrome of nephrogenic antidiuresis (NSIAD), central diabetes insipidus (CDI), or nephrogenic diabetes insipidus (NDI).In 6 patients with CDI, 7 patients with NDI, 7 patients with SIADH, and 2 patients with NSIAD we had the opportunity to have 24-hour urine collections during normal diet before any treatment. We had two 24-hour urine collections with a difference of at least 20% in solute output (measured by the formula urine osmolality × urine volume). In 1 patient with NDI taking a high protein diet we analyzed the effect of a normal protein intake on diuresis. With respect to patients with NDI and CDI we included only patients with a urine osmolality lower than 110 mOsm/kgHWhen the data of the patients with CDI/NDI were pooled, a high correlation between urine volume and solute output was observed (R = 0.83; p0.001). In 1 patient with X-linked NDI, we decreased urine volume simply by decreasing protein intake. If we pooled the data concerning SIADH/NSIAD, a correlation was observed between urine volume and solute output (R = 0.94; p0.001). As expected, increasing solute intake is beneficial in SIADH/NSIAD, while decreasing it decreases diuresis in NDI.Daily variations in solute output affect urine volume in NDI/CDI/SIADH/NSIAD, this could affect serum sodium (SNa) despite no variation in fluid intake. In SIADH, if solute intake is lower than usual for a few days it may significantly influence the SNa level despite no variation in fluid intake.

Background: Chronic hyponatremia has been reported to be associated with low solute intake and low creatinine excretion (reflecting likely sarcopenia). We wanted to study the effect, on the long term, of correction of hyponatremia on solute and creatinine excretion in chronic SIADH. Methods: We made a retrospective review of clinical and biochemical data of patients with euvolemic hyponatremia. We analyzed 24-h urine solute and creatinine excretion in volunteers with hyponatremia induced by dDAVP over 4 days, in 12 patients with chronic SIADH (>1 month) before and after a few days of SNa correction and in 12 patients (6 women and 6 men) before and after 3 months of SNa correction by a vaptan or urea. Results: We confirm a low urine creatinine and solute excretion only in patients with chronic hyponatremia (>1 month). Correction of SNa (from 127 ± 2.3 mEq/L to 139 ± 2.8 mEq/L) for >3 months, in the 12 patients (mean age 58 ± 18), was associated with an increase in 24-h creatinine excretion (from 986 ± 239 to 1,238 ± 220 mg; p < 0.02) and in patients treated with a vaptan (n = 5) solute excretion increased from 656 ± 207 mmol/24 h to 960 ± 193 mmol/24 h (p < 0.02). Sodium excretion increased also in the 12 patients (from 100 ± 53 mEq/24 h to 169 ± 38 mEq/24 h; p < 0.01). Conclusion: Chronic hyponatremia (>1 month) is associated with a decrease in solute output (or intake) and in creatinine excretion. In many patients, these abnormalities are reversible in the long term.

Introduction: Hyponatremia is the most common fluid and electrolyte abnormality. It is associated with much higher morbidity and mortality rates than found in non hyponatremic patients.Areas covered: When the physician is faced to a hyponatremic patient he first has to confirm that hyponatremia is associated with hypoosmolality. Then he must answer to a series of questions: What is its origin? Is it acute or chronic? Which treatment is the most appropriate? We will discuss the various options for the treatment of hypotonic hyponatremia. For a better comprehensive approach of the treatment we will also discuss some pathophysiological data. The use of urea in euvolemic and hypervolemic hyponatremia will be particularly discussed. Literature was reviewed from Jan 1970 to Dec 2019.Expert opinion: Prospective studies showing the benefit in decreasing morbidity by increasing SNa in patients with chronic hyponatremia should be done. These studies should also compare the efficacy and side effects of urea therapy compare to vaptans.

The differential diagnosis between hypertonic, isotonic and hypotonic hyponatremia are presented. The help of some usual serum (urea, uric acid and TCO2) and urine parameters (mainly osmolality and sodium concentration) are discussed and help to determine the best treatment. Morbidity associated with untreated hyponatremia and with the different treatment available is also discussed. Who to prevent and treat ODS (osmotic demyelating syndrome) is recalled. The pathophysiology and treatment of hypernatremia are also discussed.

Background Treatment options for chronic SIADH include water restriction (WR) and urea. The usefulness of urine osmolality to guide the choice of the treatment option is not clearly defined. We hypothesized that urine osmolality can indicate whether treatment with mild water restriction alone could be successful. Methods Retrospective Review of clinical and biochemical (blood and urine) data of patients with chronic SIADH treated for at least one year with mild WR (1.5–2 l/day) either with or without urea. Results Twenty nine patients were included. Nine patients were treated by mild WR. Mean serum sodium (SNa) and mean Uosm were 129 ± 2 mEq/l and 274 ± 78 mOsm/kgH2O respectively before WR, and increased to 138.5 ± 3 mEq/l and 505 ± 87 mOsm/kgH 2 O ( P 2 O respectively and increased to 136.5 ± 1 mEq/l and 490 ± 151 mOsm/kgH 2 O ( P 2 O and increased to 136.5 ± 2 mEq/l and 698 ± 157 mOsm/kgH 2 O ( P Conclusions About 30% of patients could be treated by moderate WR alone. All these patients presented an initial urine osmolality lower than 400 mOsm/kgH 2 O.

Hyponatremia is defined by low serum sodium concentration and is the most common electrolyte disorder encountered in clinical practice. Serum sodium is the main determinant of plasma osmolality, which, in turn, affects cell volume. In the presence of low extracellular osmolality, cells will swell if the adaptation mechanisms involved in the cell volume maintenance are inadequate. The most dramatic effects of hyponatremia on the brain are seen when serum sodium concentration decreases in a short period, allowing little or no adaptation. The brain is constrained inside a nonextensible envelope; thus, brain swelling carries a significant morbidity because of the compression of brain parenchyma over the rigid skull. Serum sodium concentration is an important determinant of several biological pathways in the nervous system, and recent studies have suggested that hyponatremia carries a significant risk of neurological impairment even in the absence of brain edema. The brain can also be affected by the treatment of hyponatremia, which, if not undertaken cautiously, could lead to osmotic demyelination syndrome, a rare demyelinating brain disorder that occurs after rapid correction of severe hyponatremia. This review summarizes the pathophysiology of brain complications of hyponatremia and its treatment., SCOPUS: re.j, info:eu-repo/semantics/published

Background: In hyponatremia, due to the inappropriate secretion of antidiuretic hormone (SIADH), a high versus low solute intake will affect the urine volume (UV) and, hence, the SNa level. The clinical implication of the fractional solute excretion is presented. Methods: In 35 normal controls and 24 patients with SIADH and urine osmolality higher than serum osmolality, we compared exact solute intake obtained from 24 h urine collection, with the estimated value obtained on a urine morning spot sample by the formula: eGFR (L/min) &times, Sosm &times, 1440 &times, FE.Osm (%) = mmol/24 h. The exact UV was compared with the estimated value given by the formula: eGFR &times, S.Creat/U.Creat (for eGFR the MDRD was used). In 65 patients with chronic SIADH, from which a morning spot urine sample was available, we determined the estimated fluid and solute intake. Results: A good correlation was observed between the measured solute output or urine volume and the estimated values obtained from the controls (r = 0.86) as well as in SIADH (r = 0.91). Conclusion: Patients with low solute intake (FE.Osm &lt, 1.4%) and low diuresis (V/eCcr &lt, 0.8%) should increase their intake by taking oral urea, for example. Patients with high solute intake (FE.Osm &gt, 2.5%) and high diuresis (V/eCcr &gt, 1.5%) could usually be treated by mild water restriction (&lt, 1.5&ndash, 21/24 h).

AIMS We attempted to classify 115 consecutive nonedematous hyponatremic patients according to their history and saline responsiveness. We hereby describe 6 out of them presenting a transient renal salt wasting (TRSW) state of unknown origin. MATERIALS AND METHODS Six patients with an initial SNa of 126 ± 3 mEq/L were included in the study. They were treated with 2 L isotonic saline infusion over 24 hours. The evolution of the biochemical data of 5 patients were compared to 6 patients with syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIADH), 6 hyponatremias following the use of thiazides, and to 5 salt-depleted hyponatremic patients of similar age and body weight, treated in the same way. RESULTS The mean values of FEurea and FEuric acid in the 6 described patients, together with a clearly inappropriate natriuresis suggested SIADH. However, the high mean fractional potassium excretion (FEK = 34 ± 15%) was not observed in SIADH (13 ± 3%) (p < 0.01). Plasma sodium levels improved quickly after saline infusion in most of these patients, while fractional solute excretions and diuresis decreased. Calciuria is increased in patients with renal salt waisting (RSW), while low calciuria values are observed in the thiazide group. Four of the 6 hyponatremic patients were admitted for syncopal malaise or fall. CONCLUSION We observed in 6 out of 115 consecutive hyponatremic patients a TRSW. RSW as a diagnosis has to be considered when in hyponatremia with excessive natriuresis, high FEK and an intake of diuretics is ruled out. This hyponatremia is saline-responsive, but relapse can be frequently observed.

Background/AIMS: Hyponatremia secondary to distal diuretics intake could have a biochemical picture similar to the one observed in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In these patients, water retention is considered to be the main causal factor and solute depletion a secondary one. Methods. We compared the level of cation (Na + K) depletion and water balance in patients with high or low uric acid levels (< 4 mg/dL or 238 µmol/L) or with high or low (< 30 mg/dL or 5 mmol/L) urea levels. Data were collected from 15 consecutive patients treated in a similar way by a daily infusion of 2 L isotonic saline with potassium chloride until SNa reached at least 132 mmol/L. The same procedure was performed in 6 patients with hyponatremia due to salt depletion not related to diuretic intake. Results: Hyponatremia, associated with low or high uric acid level is mainly due to severe cation depletion (around 600 mmol) and not due to water retention, since body weight did not change significantly (SNa 122 ± 2.0 mEq/L). If patients were classified according to serum urea levels those with higher urea levels (≥30 mg/dL) presented with a mild increase in BW (0.84 ± 0.37 kg). In patients with salt depletion and hyponatremia not related to diuretic intake, we observe as expected an increase in BW (1.5 ± 0.3 kg) and similar cation retention with the treatment. Conclusion: We therefore suggest that diuretic induced hyponatremia with an SIADH-like biochemical profile, should be treated mainly by solute ­repletion.

Adequate protein folding is necessary for normal cell function and a tightly regulated process that requires proper intracellular ionic strength. In many cell types, imbalance between protein synthesis and degradation can induce endoplasmic reticulum (ER) stress, which if sustained, can in turn lead to cell death. In nematodes, osmotic stress induces massive protein aggregation coupled with unfolded protein response and ER stress. In clinical practice, patients sustaining rapid correction of chronic hyponatremia are at risk of osmotic demyelination syndrome. The intense osmotic stress sustained by brain cells is believed to be the major risk factor for demyelination resulting from astrocyte death, which leads to microglial activation, blood-brain barrier opening, and later, myelin damage. Here, using a rat model of osmotic demyelination, we showed that rapid correction of chronic hyponatremia induces severe alterations in proteostasis characterized by diffuse protein aggregation and ubiquitination. Abrupt correction of hyponatremia resulted in vigorous activation of both the unfolded protein response and ER stress accompanied by increased autophagic activity and apoptosis. Immunofluorescence revealed that most of these processes occurred in astrocytes within regions previously shown to be demyelinated in later stages of this syndrome. These results identify osmotic stress as a potent protein aggregation stimuli in mammalian brain and further suggest that osmotic demyelination might be a consequence of proteostasis failure on severe osmotic stress., SCOPUS: ar.j, info:eu-repo/semantics/published

Patients with diabetes mellitus experience a large number of falls and bone fractures that are not related solely to complications of the disease. The purpose of our study was to determine whether transient hyperglycemia affects attentional functions and gait. This was a case–control study. We asked 17 patients with type 1 or type 2 diabetes mellitus to perform three visual tests and one visual and auditory attention test (Phasic Alert A1-4 and A2-3, Go/No Go, Intermodal Comparison). Mean response time (ms) and total number of errors were assessed. Ten of the patients also performed a tandem gait test consisting of three steps. The total distance travelled (TDT, in mm) by the center of pressure was measured with a pressure-sensitive calibrated platform. Transient hyperglycemia was defined as blood glucose level greater than 13, 8 mmol/L at the time of the test. These same patients were retested 1–3 days later at a blood glucose level at least 5, 5 mmol/L lower than the initial values (T24-72h). Nineteen patients with diabetes mellitus were matched with the original participants and performed the same test under normoglycemic conditions. During transient hyperglycemia, the mean response time (ms) and the TDT were significantly longer. The mean response time for the four tests increased by 53, 5 ms (P

info:eu-repo/semantics/published

Hyponatraemia, defined as a serum sodium concentration, SCOPUS: ar.j, info:eu-repo/semantics/published

Hyponatremia is the most common electrolyte disorder in clinical practice. Its incidence increases with age and it is associated with increased morbidity and mortality. Recently, the vaptans, antagonists of the arginine vasopressin pathway, have shown promise for safe treatment of hyponatremia. Here we evaluated the efficacy, safety, and tolerability of oral lixivaptan, a selective vasopressin V2-receptor antagonist, for treatment of nonhospitalized individuals with euvolemic hyponatremia (sodium less than 135 mmol/l) in a multicenter, randomized, double-blind, placebo-controlled, phase III study. About half of the 206 patients were elderly in a chronic care setting. Of these patients, 52 were given a placebo and 154 were given 25-100 mg per day lixivaptan, titrated based on the daily serum sodium measurements. Compared with placebo (0.8 mmol/l), the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 (primary efficacy endpoint) with lixivaptan treatment. A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium (39.4%) by day 7 relative to placebo (12.2%). Overall, lixivaptan was considered safe and well-tolerated. Thus, oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia.

Erdheim-Chester disease (ECD) is a non-Langerhans’ histiocytosisand a veryrare multisystemic disease of unknown aetiology, with skeletal involvement of the long bones and in more than 50% of cases with extraskeletal involvement. The disease was described in 1930 by the anatomopathologist Jakob Erdheim and his student William Chester. More than 500 cases have since been reported. We report the case of a 77-year-old Italian woman with ECD who was admitted to hospital for acute cardiac tamponade. The patient presented with simultaneous cutaneous, retro-orbital, skeletal, cerebral and cardiovascular manifestations and was successfully treated with corticosteroids followed by interferon. LEARNING POINTS Erdheim-Chester disease (ECD) is a non-Langerhans’ histiocytosisand a very rare multisystemic disease that is thought to be associated with cytokine disturbances. ECD has a variable prognosis but is poorer in those with heart involvement. First-line treatment involves the administration of interferon alpha.

Summary Background and objectives Vaptans (vasopressin V2-receptor antagonists) are a new approach for the treatment of hyponatremia. However, their indications remain to be determined, and their benefit compared with that of the usual treatments for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not been evaluated. This prospective, long-term study compared the efficacy, tolerability, and safety of two oral vaptans with those of oral urea in patients with SIADH. Design, setting, participants, & measurements Patients with chronic SIADH of various origins were treated first with vaptans for 1 year. After an 8-day holiday period, they received oral urea for an additional 1-year follow-up. Serum sodium was measured every 2 months, and drug doses were adjusted accordingly. Results Thirteen participants were initially included in the study (serum sodium, 125±3 mEq/L); 12 completed the 2-year treatment period. Treatment with vaptans (satavaptan, 5–50 mg/d, n=10; tolvaptan, 30–60 mg/day, n=2) increased natremia (serum sodium, 135±3 mEq/L) during the 1-year vaptan period without escape. Hyponatremia recurred in the 12 participants when vaptans were stopped (holiday period). Urea improved the natremia with the same efficacy (serum sodium, 135±2 mEq/L) as vaptans during the 1-year urea treatment period. One participant treated with tolvaptan withdrew from the study early because of excessive thirst. Another patient receiving urea developed hypernatremia without complications. Conclusions Urea has efficacy similar to that of vaptans for treatment of chronic SIADH. Tolerance is generally good for both agents.

Resume Les vaptans sont des antagonistes non peptidiques des recepteurs a l’arginine-vasopressine. Certains d’entre eux sont suffisamment loin dans leurs developpements cliniques pour etre sur le marche. Dans l’Union europeenne, seul le tolvaptan a recu l’autorisation dans le traitement de l’hyponatremie liee a un SIADH. La place de cet antagoniste du recepteur V 2 est comparee aux autres traitements (la restriction hydrique, la demeclocycline, le furosemide et l’uree).

Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination.

Two vasopressin antagonists (‘vaptans') are now in the market for the treatment of euvolemic (Europe) or euvolemic and hypervolemic (United States) hyponatremia: conivaptan for intravenous use and tolvaptan for oral application. Although their specificity and effectiveness are considered established, their indications are not. At present, we do not know which symptoms of hyponatremia and which degree of hyponatremia should serve as indications for vaptans. Other areas of uncertainty relate to the following unanswered questions: do vaptans shorten the duration of hospitalization? Is it justifiable to use them to prevent relapse of hyponatremia in (chronic) SIAD(H)? (In this text we use the abbreviation SIAD(H) instead of the recently proposed abbreviation SIAD to emphasize that vaptans will work only in the presence of ADH (‘SIADH') but not in the syndrome of nephrogenic antidiuresis.) Do they decrease the high mortality associated with hyponatremia? How do we justify the cost of chronic vaptan therapy? The optimal vaptan regimen (dose, timing of controls) to treat SIAD(H) is currently not established, as is the procedure to be recommended in a too rapid correction rate of (chronic) hyponatremia. Until these requirements shall be met by additional studies, we are hesitant to consider vaptans a treatment of choice for the appropriate hyponatremias.

Background Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described entity, linked to gain-of-function mutations (R137C and R137L) in arginine vasopressin (AVP) gene leading to chronic activation of tubular V2 AVP receptor (V2R) and thus free water reabsorption. In addition to collecting duct cells, the V2R is also expressed in endothelial cells, where it mediates the rise in circulating levels of von Willebrand factor (vWF) and coagulation factor VIII (fVIII). Recent in vitro data showed that these mutant receptors are resistant to vasopressin-stimulated cAMP production. We aimed to explore by clinical observations the sensitivity to vasopressin of the R137C-V2R mutant in vivo. Material and methods We performed a stimulation test with 1-desamino-d arginin vasopressin (dDAVP) 0·3μg/kg of bodyweight in three patients (two hemizygous male and one heterozygous female) with NSIAD with R137C mutation and measured on the one hand the levels of vWF and fVIII and the other hand urine osmolality and albumin excretion (UAE). Results Whereas the female heterozygous patient displayed normal response to simulation by dDAVP (except for UAE), no increase in vWF, fVIII, urinary osmolality and UAE was observed among hemizygous male patients. Conclusions Coherent with in vitro observation in transfected cells, our clinical observations demonstrate that the R137C-V2R mutant is resistant to vasopressin stimulation in its physiological sites of expression. © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

The management of hypotonic hyponatremia depends on its cause and its severity. The cases of hyponatremia with decreased, increased and normal extracellular fluid (ECF) volumes will be examined, followed by a brief mention concerning severe hyponatremia.

In most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V1A/V2-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.Eighty-three patients with serum [Na] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days.Conivaptan increased the baseline-adjusted area under the serum [Na]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na] of 6 mEq/L or greater or normal serum [Na] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia.Oral conivaptan was effective in increasing serum [Na] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.

Arginine-vasopressin is a hormone that plays an important part in circulatory and water homoeostasis. The three arginine-vasopressin-receptor subtypes--V1a, V1b, and V2--all belong to the large rhodopsin-like G-protein-coupled receptor family. The vaptans are orally and intravenously active non-peptide vasopressin receptor antagonists that are in development. Relcovaptan is a selective V1a-receptor antagonist, which has shown initial positive results in the treatment of Raynaud's disease, dysmenorrhoea, and tocolysis. SSR-149415 is a selective V1b-receptor antagonist, which could have beneficial effects in the treatment of psychiatric disorders. V2-receptor antagonists--mozavaptan, lixivaptan, satavaptan, and tolvaptan--induce a highly hypotonic diuresis without substantially affecting the excretion of electrolytes (by contrast with the effects of diuretics). These drugs are all effective in the treatment of euvolaemic and hypervolaemic hyponatraemia. Conivaptan is a V1a/V2 non-selective vasopressin-receptor antagonist that has been approved by the US Food and Drug Administration as an intravenous infusion for the inhospital treatment of euvolaemic or hypervolaemic hyponatraemia.

We report the case of a 60-year-old man who presented with sudden visual loss, a history of postprandial abdominal pain, malabsorption, and skin lesions typical of systemic Degos’ disease. Despite anti-aggregants and prednisone the patient’s status did not improve. On the basis of the hypothetical dysimmune origin of this disease, we attempted treatment with intravenous immunoglobulins, without success. We then administered infliximab (Remicade®), but 2 months after the third injection the patient developed mesenteric infarction and died. We therefore believe that both intravenous immunoglobulins and antiTNFa are ineffective for the treatment of Degos’ disease.

Background: Mild hyponatremia is the commonest electrolyte imbalance in the older population and has been shown to be associated with gait and attention deficits resulting in higher frequency of falls. The association of mild hyponatremia and bone fracture is still unknown. Objective: To determine if mild hyponatremia is associated with increased risk of bone fracture in ambulatory elderly. Design, setting and participants: Case control study of 513 cases of bone fracture after incidental fall in ambulatory patients aged 65 or more in general university hospital. Controls were age and sex matched randomly selected ambulatory patients without history of bone fracture. Main exposure measures: Odds ratio (OR) of bone fracture after incidental fall associated with presence of hyponatremia. Results: Prevalence of hyponatremia (serum sodium

Brain damage (myelinolysis) develops in hyponatraemia after a large increase in serum sodium regardless of the currently available methods of correction. However, a preliminary study suggests that treatment of hyponatraemia with urea limits the risks of brain lesions in rats. Benefits of sustained high blood levels of urea and mechanisms of protection remain hypothetical.In the first part of the study, hyponatraemic rats received repeated (i.p.) doses of urea (2 g/kg b.w./6 h) leading to sustained blood levels (urea+/-230 mg/dl). Neurologic outcome was compared to correction of hyponatraemia by water diuresis. In the second part of the study, we analysed the adaptative response of the brain to correction of hyponatraemia with either urea or water diuresis, by measurement of cerebral osmolyte contents.Despite a large correction of the serum sodium (mean Delta SNa=32 mEq/l/24 h), mortality rate (13%) and neurological symptoms were low in the urea-treated group contrary to control groups treated by water diuresis (mortality: 87%). This shows with stronger evidence the protective effect of urea against brain myelinolysis. In the second part, analysis of brain composition shows that, in the urea groups, 24 h after correction, intracerebral hyperionization (NaCl) was avoided and brain water contents remained normal. No significant changes of the major brain organic osmolyte composition were observed after urea administration except reaccumulation of betaine. No difference in brain composition was noted regarding concomitant plasma urea levels (or150 mg/dl). In rats treated by water diuresis, the brain remained also significantly depleted in organic osmolytes 24 h after correction, but contrary to administration of urea, this treatment was associated with a high mortality rate.These comparative results suggest a specific brain-protective effect of urea itself against myelinolysis.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently described genetic cause of hyponatremia in male infants. Whether this X-linked condition could be detected in the adult or also could affect women is unknown. A large five-generation family was identified in which the recently described arginine-vasopressin receptor type 2 (AVPR2) mutation that is responsible for NSIAD was segregated. The proband was a 74-yr-old patient who had a syndrome of inappropriate antidiuresis and whose hyponatremia resisted administration of two AVPR2 antagonists. The phenotype of family members who carry the mutation was investigated. Patients with normal serum sodium were subjected to a water-load test. The previously reported activating missense R137C mutation in the AVPR2 gene in three hemizygous male and four heterozygous female individuals was identified. Except in one woman, spontaneous episodes of hyponatremia or abnormal water-load test were identified in all patients with the mutation, whether male or female. Skewed X inactivation was evidenced in the blood of the asymptomatic woman, which is compatible with preferential inactivation of her mutated allele. NSIAD is not limited to male infants. The diagnosis also should be considered in both male and female adults.

Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies.In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to-moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (125 mmol/L) before and after the normalization of natremia.No significant change in muscle strength was observed when natremia was corrected from 127·7 ± 2·5 to 136·1 ± 1·8 mmol/L, contrary to a significant improvement in TUG from 14·9 ± 5·1 to 12·5 ± 4·7 s (P = 0·006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121·9 ± 2·4 to 135·5 ± 3·4 mmol/L (e.g. mean increase of 14·3% for motor nerve conduction and mean decrease of 21·6% for F-wave latency of left peroneal nerve).Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia.

Hyponatremia, defined as a serum sodium concentration135mmol/l, is the most common water-electrolyte imbalance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from mild to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay. Despite this, the management of hyponatremia patients remains problematic. The prevalence of hyponatremia in a wide variety of conditions and the fact that hyponatremia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and specialty-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed clinical practice guidelines on the diagnostic approach and treatment of hyponatremia as a joint venture of 3societies representing specialists with a natural interest in hyponatremia. In addition to a rigorous approach to the methodology and evaluation of the evidence, the document focuses on patient-positive outcomes and on providing a useful tool for clinicians involved in everyday practice. In this article, we present an abridged version of the recommendations and suggestions for the diagnosis and treatment of hyponatremia extracted from the full guide.

Hypertrophic Osteoarthropathy is classically associated with chronic pulmonary disease, cancer or inflammatory bowel disease. However, deep infection such as vascular graft infection is an etiology important to recognize because of the risk of life-threatening complication (aorto-enteric fistula). In this study, we reported two cases of aortic graft infection and one case of para-anal abscess associated with hypertrophic osteoarthropathy. The previously reported cases are reviewed.

Inadequate treatment of severe hyponatremia (120 mEq/L) can be associated with severe neurological damage. In acute (48 hours) hyponatremia, usually observed in the postoperative period, prompt treatment with hypertonic saline (3%) can prevent seizures and respiratory arrest. For patients with chronic (48-72 hours) symptomatic hyponatremia, correction must be rapid during the first few hours (to decrease brain edema) followed by a slow correction limited to 10 mmol/L over 24 hours to avoid the development of osmotic demyelinating syndrome. In patients with asymptomatic hyponatremia, slow correction is the appropriate approach. When patients are overtreated, neurologic damage can be prevented by relowering the serum sodium (SNa) so that the daily increase in SNa remains below 10 mmol/L/24 hours. Frequent measurements of SNa during the correction phase of SNa are mandatory to avoid overcorrection. The use of urea to treat hyponatremia represents an advantageous alternative to hypertonic saline.

Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH) or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS) in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done., SCOPUS: ar.j, info:eu-repo/semantics/published

VPA-985 is an orally active, competitive vasopressin V(2) receptor antagonist that in normal human beings increases water excretion without affecting solute excretion. Whether solute excretion is affected in patients with hyponatremia resulting from inappropriate secretion of antidiuretic hormone (SIADH) or from cirrhosis treated with VPA-985 is unknown. Six hyponatremic patients with SIADH and 5 hyponatremic patients with cirrhosis with ascitis (CWAs) were treated with 50 or 100 mg VPA-985 twice daily. Evolution of creatinine, urea, uric acid, sodium, potassium, and osmotic clearance were determined. Volume hormones (plasma renin [PR], aldosterone, antidiuretic hormone [ADH], atrial natriuretic factor [ANF]) were also determined before and after treatment. In patients with SIADH, serum sodium concentration (SNa) was generally corrected in 1 day (SNa: 126 +/- 4.5 mmol/L at t = 0 hours and 133 +/- 5.6 mmol/L at t = 24 hours) and associated with a decrease in sodium excretion (from 82 +/- 22 mmol/24 hours to 45 +/- 21 mmol/24 hours; P < 0.05) without modification in potassium excretion. Despite an increase in diuresis (from 0.84 +/- 0.2 ml/min to 1.46 +/- 0.4 ml/min) urea and uric acid clearances decreased. Urine osmolality decreased from 414 +/- 148 mOsm/kg H(2)O to 209 +/- 55 mOsm/kg H(2)O. Volume hormones did not change. In the CWAs the rise of SNa was more progressive (SNa: 126 +/- 2.8 mmol/L at t = H0 to 133 +/- 4.9 mmol/L at t = 48 hours) and parallel to an augmentation in sodium excretion (from 23 +/- 18 mmol/24 hours to 65 6 60 mmol/24 hours the second day of VPA administration). The higher sodium excretion was also connected with a progression in potassium excretion (from 22 6 7 mmol/24 hours to 36 +/- 18 mmol/24 hours). The increase in diuresis under VPA from 0.42 +/- 0.2 mL/min to 1.7 +/- 0.9 mL/min resulted in a higher urea clearance. Urine osmolality decreased from 509 +/- 142 mOsm/kg H(2)O before VPA to 194 +/- 106 mOsm/kg H(2)O after VPA. ADH increased in CWAs treated with VPA, from 1.9 +/- 1.2 pg/mL to 5.3 +/- 2.8 pg/mL (P

Azathioprine (AZA) is characterized by a high interindividual variability in bioavailability and metabolism. AZA is converted into 6-thioguanine nucleotides (6-TGN) to which the immune modifier activity is attributed. The 6-TGN levels are known to be affected by the activity of the key enzyme, thiopurine methyltransferase (TPMT), which is under genetic dependence. The authors measured a significantly lower TPMT activity in 53 women with systemic lupus erythematosus (SLE) (12.2 +/- 2.4 pmol/h/ml RBC; P < 0.01) when compared with 30 healthy control participants (13.15 +/- 3.1 pmol/h/ml RBC) but not with 28 patients with other dysimmune diseases (non-SLE; 13.0 +/- 3.0 pmol/h/ml RBC; P = 0.10). To evaluate the impact of TPMT activity on the concentrations of AZA metabolites, we measured the TPMT activity and 6-TGN levels in a subgroup of 26 patients in remission and treated with a stable dose of AZA (mean value: 1.9 +/- 0.5 mg/kg/day) for at least six months (n = 13 with SLE and n = 13 with other dysimmune diseases, ie, non-SLE). In such a subgroup, no correlation between 6-TGN levels and TPMT activity was observed. However, patients with SLE presented lower TPMT activity and higher 6-TGN levels (215 +/- 123 versus 140 +/- 75 pmol/8 x 10(8) RBC in non-SLE patients; P < 0.04). It must be noted that transient increase in 6-methylmercaptopurine levels (6-MMP), a putative toxic metabolite (up to 21.7 nmol/8 x 10(8) RBC), was more frequently observed in the non-SLE group (P < 0.01). Even if a relationship was observed between low TPMT activity and 6-TGN levels in SLE, its clinical impact appears to be limited as far as regular hematologic controls are performed.