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Background: Hyponatremia is the most common elec- trolyte disorder, but a lack of well-characterized co- horts is hindering a full appreciation of this complex and heterogeneous disorder. Methods: During 4 months, clinical, biochemical, treat- ment and outcome data were collected for patients presenting with hyponatremia (serum sodium ≤130 mmol/L) to an urban university hospital. Results: Forty-three patients were included (serum so- dium 126.6 ± 3.7 mmol/L). The most common causes of hyponatremia were diuretics (n=12), syndrome of inappro- priate antidiuretic hormone secretion (n=11) and heart or liver disease (n=5). Renal insufficiency was frequent (n=18, 42%), and usually represented acute kidney injury (AKI; n=14, 78%). In patients with AKI, admission serum crea- tinine was 271 ± 252 μmol/L (3.4 ± 3.1-fold increase from baseline) and the origin was usually prerenal (12/14, 86%, fractional sodium excretion 0.54% ± 0.38%). Of these, pa- tients with potentially reversible causes (salt loss or sep- sis, n=7) had more favorable outcomes than patients with severe underlying disease (heart or liver disease, n=5), despite similar predictions using the RIFLE criteria. Sur- vivors recovered with fluid resuscitation only. No overly rapid correction of hyponatremia was observed. Conclusions: AKI is common in patients presenting with hyponatremia and is usually of prerenal origin. The concurrence of AKI and hyponatremia has previously not been emphasized, but is important pathophysi- ologically and to plan rational management for both disorders. In this cohort, isotonic fluid replacement corrected both disorders and did not lead to overly rapid correction of hyponatremia.

We report the case of a 25-year-old patient with systemic lupus erythematosus (SLE) pancreatitis which was complicated by pseudocyst and pseudoaneurysm formation. The pseudoaneurysm progressed to intra-abdominal bleeding requiring endovascular coil embolization of the gastroduodenal artery. The pseudocyst and hematoma formed two large abdominal fluid collections causing symptoms due to a mass effect. These fluid collections were treated conservatively, while active SLE was treated with steroids, azathioprine, and immunoglobulins. She finally made a full recovery. To the best of our knowledge, this is the first report of a bleeding pseudoaneurysm complicating SLE pancreatitis. Although anecdotal, this case may serve as a useful example of the possible complications of SLE pancreatitis, including considerations on optimal management. Lupus (2011) 20, 305-307.

Despite a crucial role in body fluid homeostasis, elevated vasopressin levels can also be pathological in conditions such as congestive heart failure, liver cirrhosis and the syndrome of inappropriate antidiuretic hormone secretion. The result of elevated vasopressin is renal water retention and hyponatremia, a low serum sodium concentration. Hyponatremia is associated with excess morbidity and mortality. Nonpeptide vasopressin-receptor antagonists represent a new drug class of small molecules that competitively inhibit one or more of the vasopressin receptors. There are three vasopressin receptors in humans, including V1a, V1b and V2. Selective V2- and combined V1a/V2-receptor antagonists have been developed for the treatment of hyponatremia resulting from congestive heart failure, liver cirrhosis and the syndrome of inappropriate antidiuretic hormone secretion. Two nonpeptide vasopressin-receptor antagonists, conivaptan and tolvaptan, have recently been approved by American and European drug authorities for clinical use. This article aims to provide a succinct and clinical update on nonpeptide vasopressin-receptor antagonists, including their mechanism of action, performance in randomized clinical trials and current clinical status.

In 2002 a 73-year-old woman (non-smoking, medical history of allergic rhinitis) was referred to a rheumatologist because of synovitis of the metacarpophalangeal and proximal interphalangeal joints of both hands which had slowly developed over 3 months. Late-onset rheumatoid arthritis was suspected. Morning stiffness, rheumatoid nodules, erosions of cartilage or bone, rheumatoid factor and antibodies to cyclic citrullinated peptides were absent. Prednisone (2.5–5 mg daily) and non-steroidal anti-inflammatory drugs were started. In 2004 she was referred …

Water balance disorders after neurosurgery are well recognized, but detailed reports of the triphasic response are scarce. We describe a 55-year-old woman, who developed the triphasic response with severe hyper- and hyponatraemia after resection of a suprasellar meningioma. The case illustrates how sudden and dramatic the changes in water balance after neurosurgery can be. The biochemical profile suggested central diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion. The underlying pathophysiology was further analysed using fractional excretions, measurements of renin, aldosterone and vasopressin and a metyrapone test. Diagnostic, therapeutic and preventive strategies for these intriguing but complex cases are proposed.

Background Hyponatraemia (serum sodium < 135 mmol/L) has long been recognized as a complication of malaria. However, few studies have been done in non-immune adult populations. It has not been investigated previously how hyponatraemia is distributed among the various Plasmodium species, and its association with malaria severity is unknown. The aim of this retrospective cohort study was to determine the prevalence of hyponatraemia and its association with malaria severity in a large cohort of patients with imported malaria caused by various Plasmodium species. Methods All patients that were diagnosed with malaria in the Harbour Hospital and Institute for Tropical Diseases in Rotterdam in the period 1999-2009 and who had available serum sodium on admission were included. Severe malaria was defined according to the modified WHO criteria. Prevalence of hyponatraemia and its association with malaria severity were investigated by univariate comparison, ROC analysis and multivariate logistic regression analysis. Results A total of 446 patients with malaria (severe falciparum malaria n = 35, non-severe falciparum malaria n = 280, non-falciparum malaria n = 131) was included. Hyponatraemia was present in 207 patients (46%). Prevalence and severity of hyponatraemia were greatest in severe falciparum malaria (77%, median serum sodium 129 mmol/L), followed by non-severe falciparum malaria (48%, median serum sodium 131 mmol/L), and non-falciparum malaria (34%, median serum sodium 132 mmol/L). Admission serum sodium < 133 mmol/L had a sensitivity of 0.69 and a specificity of 0.76 for predicting severe malaria. Multivariate logistic regression showed that serum sodium < 131 mmol/L was independently associated with severe falciparum malaria (odds ratio 10.4, 95% confidence interval 3.1-34.9). In patients with hyponatraemia, hypovolaemia did not appear to play a significant role in the development of hyponatraemia when prerenal azotaemia and haematocrit were considered as surrogate markers for hypovolaemia. Conclusions Hyponatraemia is common in imported malaria and is associated with severe falciparum malaria. From a clinical point of view, the predictive power of hyponatraemia for severe malaria is limited. The precise pathophysiological mechanisms of hyponatraemia in malaria require further study.

The vasopressin-receptor antagonists have received approval for the treatment of hyponatraemia secondary to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). It is therefore necessary that physicians encountering hyponatraemia focus on SIADH. Recent studies show that hyponatraemia is often poorly managed - insufficient diagnostic tests are ordered and patients are undertreated. At the same time, it has become clear that chronic hyponatraemia causes neurological symptoms such as gait disturbances and attention deficits. However, physicians often tolerate chronic hyponatraemia as if it were benign, or as if its treatment would cause significant morbidity. Therefore, physicians must reconsider the diagnostic and therapeutic approaches to hyponatraemia and SIADH. The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA].2009Oxford University PressThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2. 5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A 49-year-old woman (previous history of childhood asthma, no medication) presented to the emergency department with nausea and vomiting that had occurred for 5 days and slurred speech for 1 day prior to presentation. The patient denied use of alcohol and illicit drugs. Physical examination revealed her blood pressure to be 125/70 mmHg; she had no postural drop and had a regular pulse of 72 beats/min. She had no fever and no signs of contracted extracellular fluid volume. Results of further physical and neurological examination were unremarkable and revealed no goiter, pigmentation, or vitiligo. Her laboratory results are shown in Table 1⇓ . Additional diagnostic tests included chest x-ray, abdominal ultrasound, and brain computed tomography, none of which revealed abnormalities. The syndrome of inappropriate antidiuretic hormone secretion (SIADH)1 was suspected. However, fluid restriction (500 mL/day) did not lead to increased serum sodium. View this table: Table 1. Laboratory results. Because of the lack of response to therapy for SIADH, the diagnosis was reconsidered and hypothyroidism and/or adrenal insufficiency were suspected, especially because serum glucose was also low. Serum thyroid-stimulating hormone was 63 mU/L (reference interval 0.4–4.0 mU/L) with free thyroxine of 5 pmol/L (reference interval 9–24 pmol/L; to convert pmol/L of free thyroxine to ng/dL, divide by 13). Random cortisol was 151 nmol/L (reference interval 150–700 nmol/L; to convert nmol/L of cortisol to μg/L, divide by 0.0157), and a stimulation test with the 1–24 fragment of adrenocorticotropic hormone (ACTH) showed a baseline cortisol of 56 nmol/L, which increased only to 57 nmol/L (normal response >500 nmol/L). Plasma ACTH was …

Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 +/- 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 +/- 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 +/- 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 +/- 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 +/- 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms. Am J Kidney Dis 56:112-116. (C) 2010 by the National Kidney Foundation, Inc.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) remains a challenging disorder to diagnose and treat. Three cases are presented to illustrate these challenges. The first two cases had drug-induced SIADH secondary to a selective serotonin reuptake inhibitor (for depression) or carbamazepine (for trigeminal neuralgia). The third case had SIADH possibly secondary to bronchiectasis. The lowest serum sodium concentrations ranged between 118 and 124 mmolL in the three cases. Hyponatraemia was not acute and severe symptoms were absent. However, several mild neurological symptoms were present. In the first case, hyponatraemia likely contributed to a fall, which resulted in a fracture of the odontoid process of the axis. The other two cases also had gait disturbances, in addition to nausea, headache, impaired memory, difficulty concentrating and confusion. In at least two of the cases, the underlying cause of SIADH was impossible to reverse. Traditional treatment for SIADH with fluid restriction and demeclocycline failed, caused side effects or increased duration of hospital stay. These examples suggest a need for better treatment options. The introduction of the vasopressin-receptor antagonists for SIADH may be a welcome new therapy to overcome some of these challenges. The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA].2009Oxford University PressThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

In the current era of large-scale biology, proteomics has evolved as a powerful, new technique that aims to identify, quantify, and analyze a large number of proteins in a functional context. Therefore, proteomics can be used to study cellular pathways and identify disease biomarkers. In this review, we first outline the principles of two important proteomics techniques that either use difference gel electrophoresis (DIGE) or liquid chromatography (LC) for protein separation, followed by tandem mass spectrometry (MS/MS). The advantages and limitations of each technique are discussed, emphasizing the ability of DIGE to perform quantitative proteomics and the high-throughput and high-sensitivity characteristics of LC-MS/MS. We have employed both techniques to unravel the molecular machinery of vasopressin signaling, which governs water homeostasis by recruiting aquaporin-2 (AQP2) water channels after activation of the vasopressin-2 receptor by vasopressin. Several aspects of vasopressin signaling in the inner medullary collecting duct (IMCD) were investigated, including the short- and long-term regulation of AQP2, phosphoproteomics, signaling during vasopressin escape, and the proteomes of AQP2-bearing vesicles and the IMCD plasma membranes. We also emphasize that proteomics of body fluids will be the strategy to identify disease biomarkers, and therefore conclude the review by highlighting the perspectives of biomarker discovery in urinary exosomes.

In the current era of large-scale biology, proteomics has evolved as a powerful, new technique that aims to identify, quantify, and analyze a large number of proteins in a functional context. Therefore, proteomics can be used to study cellular pathways and identify disease biomarkers. In this review, we first outline the principles of two important proteomics techniques that either use difference gel electrophoresis (DIGE) or liquid chromatography (LC) for protein separation, followed by tandem mass spectrometry (MS/MS). The advantages and limitations of each technique are discussed, emphasizing the ability of DIGE to perform quantitative proteomics and the high-throughput and high-sensitivity characteristics of LC-MS/MS. We have employed both techniques to unravel the molecular machinery of vasopressin signaling, which governs water homeostasis by recruiting aquaporin-2 (AQP2) water channels after activation of the vasopressin-2 receptor by vasopressin. Several aspects of vasopressin signaling in the inner medullary collecting duct (IMCD) were investigated, including the short- and long-term regulation of AQP2, phosphoproteomics, signaling during vasopressin escape, and the proteomes of AQP2-bearing vesicles and the IMCD plasma membranes. We also emphasize that proteomics of body fluids will be the strategy to identify disease biomarkers, and therefore conclude the review by highlighting the perspectives of biomarker discovery in urinary exosomes.

Background. The objective was to study the epidemiology of hypokalaemia [serum potassium concentration (SK)

Proteomics is seeing increasing use as a means of identifying new mechanistic hypotheses in physiology. Proteomics based on two-dimensional electrophoresis (2-DE) has recently been optimized with the development of Difference Gel Electrophoresis (DIGE). In DIGE-based proteomics, the experimental and control samples are derivatized with different fluorophores and are run in the same gel, thereby minimizing technical variation. DIGE is currently one of the few techniques to perform quantitative proteomics, generating a statistical output to differences in protein abundances. In this review, we discuss the principles of DIGE-based proteomics, including sample preparation, 2-DE, statistical analysis of 2D-gels, and mass spectrometry. Strengths and weaknesses of DIGE are discussed, including possible solutions to overcome certain limitations, such as the identification of low abundance and integral membrane proteins. In addition, we provide a brief synopsis of our recent experiments in which DIGE-based proteomics was applied to study vasopressin signaling in the renal collecting duct. Finally, we illustrate how quantification based on the DIGE approach combined with bioinformatics may facilitate the study of systems biology of the kidney.

Hypokalemia is a prominent feature of Gitelman syndrome and a common side effect of thiazide use in the treatment of hypertension. It is widely recognized that genetic or pharmacological inhibition of the renal thiazide-sensitive sodium-chloride cotransporter (NCC) initiates the potentially severe renal potassium loss observed in these settings. Surprisingly, hypokalemia has not been detected in NCC (−/−) mice maintained on normal rodent diets (Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, and Shull GE. J Biol Chem 273: 29150–29155, 1998). We show that modest reduction of dietary potassium induced a marked reduction in plasma potassium and elevated renal potassium excretion in NCC (−/−) mice that was associated with a pronounced polydipsia and polyuria of central origin. These findings are consistent with the development of potassium depletion in NCC (−/−) mice and were not seen in wild-type mice maintained on the same low-potassium diet. In addition, plasma aldosterone levels were significantly elevated in NCC (−/−) mice even in the presence of a low-potassium diet. Collectively, these findings suggest an early central component to the polyuria of Gitelman syndrome and show that both elevated aldosterone and dietary potassium content contribute to the development of hypokalemia in Gitelman syndrome. Therefore, NCC (−/−) mice are more sensitive to reductions in dietary potassium than wild-type mice and become hypokalemic, thus more faithfully representing the Gitelman phenotype seen in humans.

Hoorn EJ, de Vogel S, Zietse R (Erasmus Medical Center, Rotterdam, The Netherlands). Insulin resistance in an 18-year-old patient with Down syndrome presenting with hyperglycaemic coma, hypernatraemia and rhabdomyolysis (Case report). J Intern Med 2005; 258: 285–288.

Recent progress in biotechnology offers the promise of better medical care at lower costs. Among the techniques that show the greatest promise is mass spectrometry of proteins, which can identify proteins present in body fluids and tissue specimens at a large scale. Because urine can be collected in large amounts in a non-invasive fashion, the potential exists to use mass spectrometry to discover urinary biomarkers that are early predictors of renal disease, or useful in making therapeutic choices. Recently, the authors demonstrated that both membrane proteins and cytosolic proteins from renal epithelia are highly enriched in low-density urinary structures identified as exosomes. Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+ K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be discovered by mass spectrometry-based proteomic studies in well-defined patient populations. Herein is described the advantages of using urinary exosomes as a starting material for biomarker discovery. In addition, the purpose of this review is to present an overall strategy for biomarker discovery in urine using exosomes and for developing cost-effective clinical assays for these biomarkers, which can potentially be used for early detection of disease, as a means of differential diagnosis, or as a means of guiding therapy. Finally, potential barriers that need to be overcome before urinary proteomics can be applied clinically, are emphasized.

The usual diagnostic approach to a patient with hyponatraemia is based on the clinical assessment of the extracellular fluid (ECF) volume, and laboratory parameters such as plasma osmolality, urine osmolality and/or urine sodium concentration. Several clinical diagnostic algorithms (CDA) applying these diagnostic parameters are available to the clinician. However, the accuracy and utility of these CDAs has never been tested. Therefore, we performed a survey in which 46 physicians were asked to apply all existing, unique CDAs for hyponatraemia to four selected cases of hyponatraemia. The results of this survey showed that, on average, the CDAs enabled only 10% of physicians to reach a correct diagnosis. Several weaknesses were identified in the CDAs, including a failure to consider acute hyponatraemia, the belief that a modest degree of ECF contraction can be detected by physical examination supported by routine laboratory data, and a tendency to diagnose the syndrome of inappropriate secretion of antidiuretic hormone prior to excluding other causes of hyponatraemia. We conclude that the typical architecture of CDAs for hyponatraemia represents a hierarchical order of isolated clinical and/or laboratory parameters, and that they do not take into account the pathophysiological context, the mechanism by which hyponatraemia developed and the clinical dangers of hyponatraemia. These restrictions are important for physicians confronted with hyponatraemic patients and may require them to choose different approaches. We therefore conclude this review with the presentation of a more physiology-based approach to hyponatraemia, which seeks to overcome some of the limitations of the existing CDAs.

After hand trauma and surgery, assessment of tendon excursion is important in reconstructive surgery and rehabilitation. Aimed as a more reliable alternative to traditional noninvasive methods, a colour Doppler imaging scanner was adapted to measure longitudinal tendon displacement. Displacement was quantified by integrating the velocity estimated from the zero-crossing rate of the Doppler signal. The system was tested by measuring displaced distances of a rubber string that was moved back and forth. At a determined optimal receiver gain, 1.5-cm string displacements were measured with less than +/- 0.05-cm bias throughout an echo-signal dynamic range of 22 dB; standard deviations were around 0.05 cm. Regression analysis between measured and true displacements in the range 0.5-2.5 cm resulted in a best fit straight line with slope 0.927, intercept 0.041 cm and residual standard error of 0.06 cm. A transfer technique was conceived to ensure accuracy when measuring tendons in the body. This CDI-based pulsed Doppler system merits verification for measurement of tendon excursion in patients.

Urinary exosomes are vesicles derived from renal tubular epithelial cells. Exosomes often contain several disease-associated proteins and are thus useful targets for identifying biomarkers of disease. Here, we hypothesized that the phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or spot urine using ultracentrifugation. In rats, a normal or a high dose of aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes ( P P P =0.07) than in patients with essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin are promising markers for aldosteronism in experimental animals and patients. These markers may be used to assess the biological activity of aldosterone and, potentially, as clinical biomarkers for primary aldosteronism.

The muscle-specific inflammatory response after strenuous exercise has some similarity with those observed in sepsis and it is used as a mirror of sepsis-specific inflammatory response. Near-infrared spectroscopy (NIRS) has been used to quantify sepsis-induced metabolic alterations by measuring variations of tissue oxygen saturation (StO2) during a vascular occlusion test (VOT). We aimed to investigate whether NIRS dynamic variables could reflect the magnitude of inflammatory process that follows strenuous exercise in marathon runners.

To the Editor: In their elegant review, Bakris et al.1 explored the role of selective inhibitors of sodium glucose co-transporter 2 (SGLT2) (SLC5A2, a sodium–glucose transporter in the renal proximal tubule) in diabetes mellitus type 2 (DM2). Indeed, early studies indicate that dapagliflozin is able to reduce HbA1C levels in DM2.2 However, based on our experience regarding a patient with a SLC5A2 mutation, and cases of similar patients from the literature,3 we feel some caution is warranted. Our patient is a 33-year-old Turkish man with no past medical history, and no medication or parental consanguinity. He has hypotension (90/60 mm Hg) and persistently high serum sodium and bicarbonate levels (150 and 33 mmol/l, respectively).

A data acquisition and processing system for the analysis of inert gas wash-out tests is described. The described system is in clinical use on spontaneously breathing patients as well as on mechanically ventilated Intensive Care patients. It combines several analysis techniques with an aim to provide a deeper insight into the nature of existing ventilation inhomogeneity than the individual techniques alone can provide.The signals measured are the respiratory flow, the fractions of one or two indicator gases washing out and the fractions of the metabolic gases oxygen and carbon dioxide. Analysis of these signals provides information concerning the end-expiratory lung-volume, distribution of ventilation and perfusion in the lung, the role of diffusion in the ventilation process and the metabolic oxygen uptake and CO2 release. This article describes the algorithms used and the results that are presented.

To develop hyponatremia (plasma sodium concentration (PNa) < 136 mM), there must be a source of electrolyte free water (EFW) and actions of antidiuretic hormone (ADH) to prevent its excretion. A low PNa is the most common electrolyte disorder in hospitalized children and it makes them more prone to neurological damage.

Primary Sjogren's syndrome (pSS) can be complicated by distal renal tubular acidosis (dRTA), which may contribute to low bone mineral density (BMD). Our objective was to evaluate BMD in pSS patients with and without dRTA as compared with healthy controls. BMD of lumbar spine (LS) and femoral neck (FN) was measured in 54 pSS patients and 162 healthy age-and sex-matched controls by dual-energy X-ray absorptiometry (DXA). dRTA was defined as inability to reach urinary pH

Background In the pathophysiology of hyponatraemia in malaria, the relative contribution of appropriate and inappropriate arginine vasopressin (AVP) release is unknown; the trigger for inappropriate AVP release is also unknown. Methods Serum copeptin, a stable and sensitive marker for AVP release, was analysed in a large cohort of patients with imported malaria (204 patients) and in a small prospective substudy (23 patients) in which urine sodium and osmolality were also available. Hyponatraemia was classified as mild (serum sodium 131-134 mmol/l) and moderate-to-severe (< 131 mmol/l). Results Serum copeptin on admission was higher in patients with moderate-to-severe hyponatraemia (median 18.5 pmol/L) compared with normonatraemic patients (12.7 pmol/L, p < 0.05). Despite prompt fluid resuscitation, the time to normalization of serum sodium was longer in patients with moderate-to-severe hyponatraemia (median 2.9 days) than in patients with mild hyponatraemia (median 1.7 days, p < 0.001). A poor correlation was found between serum sodium and copeptin levels on admission (rs = -0.17, p = 0.017). Stronger correlations were identified between serum C-reactive protein and copeptin (rs = -0.36, p < 0.0001) and between serum C-reactive protein and sodium (rs = 0.33, p < 0.0001). Data from the sub-study suggested inappropriate AVP release in seven of 13 hyponatraemic malaria patients; these patients had significantly higher body temperatures on admission. Conclusions In hyponatraemic patients with imported malaria, AVP release was uniformly increased and was either appropriate or inappropriate. Although the exact trigger for inappropriate AVP release remains unknown, the higher body temperatures, correlations with C-reactive protein and long normalization times of serum sodium, suggest an important role of the host inflammatory response to the invading malaria parasite.