Nephrogenic Syndrome of Inappropriate Antidiuresis
ABSTRACT The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."
- SourceAvailable from: Chih-Yang Hsu
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- "Few of our patients had data with regards to plasma arginine-vasopressin (AVP) and no one received vasopressin receptor antagonists, indicating the possibility that NSIAD may not be diagnosed. The syndrome fulfills the classic criteria of SIAD and is caused by a gain-of-functional mutation in the AVP receptor type 2, which was initially described in infants 20 and only recently reported in adult patients 21. Finally, all included objects were hospitalized patients, indicating more severe manifestations, underlying disease and co-morbidity. "
ABSTRACT: Background: Many diagnostic procedures are conducted in patients with syndrome of inappropriate antidiuresis (SIAD). However, the contribution in identification of the cause of SIAD remains unknown. Methods: The study was conducted at Kaohsiung Veterans General Hospital in southern Taiwan. From January 2000 to December 2009, medical records of 439 adult patients hospitalized for new-onset SIAD at a single center were retrospectively collected. All diagnostic procedures during hospitalization were divided into four groups: chest/lung, central nervous system, abdomen, and bone marrow to evaluate their positive rate leading to the cause of SIAD. Factors associated with “procedures leading to the cause” were also analyzed to improve efficacy of survey. Results: Cause of SIAD was identified in 267 (60.8%). Of them, 150 were pulmonary disorders, 44 were drugs, 37 were central nervous system disorders, 32 were malignancy and 4 were post-surgery. Survey for chest/lung, central nervous system, abdomen, and bone marrow were performed in 96.6%, 29.2%, 38.0% and 3.6% of patients, respectively; positive findings leading to the cause of SIAD were 39.6%, 12.5%, 5.3% and 6.3%, respectively. Among the diagnostic procedures, chest x-ray (424/439, 96.6%) was most frequently performed with the highest identification rate of 34.7% (147 cases). Major significant independent factors that associated with “procedure leading to a cause” were: absence of SIAD-associated drug history, presence of fever/chills, and presence of respiratory symptoms. Cause of SIAD became evident later during the follow-up period in 10 of 172 (5.8%) patients who were initially thought to be cause-unknown. Malignancy was the cause for 5 cases and pulmonary tuberculosis was for the other five. Eight of these causes became evident within one year after the diagnosis of SIAD. Conclusions: SIAD with unidentified causes were prevalent. Current diagnostic procedures remain not satisfying in determining the cause of SIAD, but chest radiograph did demonstrate higher diagnostic rate, especially in patients presented with fever, chills, respiratory symptoms, and without SIAD-associated drug history. Patients with unidentified cause should be followed for at least one year when most hidden causes (e.g. malignancy and tuberculosis) become obvious.International journal of medical sciences 01/2014; 11(2):192-8. DOI:10.7150/ijms.6295 · 1.55 Impact Factor
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- "Non-osmotic vasopressin secretion and abnormal thirst are present in SIADH despite a normal effective circulating volume [78,82-85]. In the critically ill patient, the mechanisms of inappropriate vasopressin secretion and thirst are heterogeneous. "
ABSTRACT: Disturbances in sodium concentration are common in the critically ill patient and associated with increased mortality. The key principle in treatment and prevention is that plasma [Na+] (P-[Na+]) is determined by external water and cation balances. P-[Na+] determines plasma tonicity. An important exception is hyperglycaemia, where P-[Na+] may be reduced despite plasma hypertonicity. The patient is first treated to secure airway, breathing and circulation to diminish secondary organ damage. Symptoms are critical when handling a patient with hyponatraemia. Severe symptoms are treated with 2 ml/kg 3% NaCl bolus infusions irrespective of the supposed duration of hyponatraemia. The goal is to reduce cerebral symptoms. The bolus therapy ensures an immediate and controllable rise in P-[Na+]. A maximum of three boluses are given (increases P-[Na+] about 6 mmol/l). In all patients with hyponatraemia, correction above 10 mmol/l/day must be avoided to reduce the risk of osmotic demyelination. Practical measures for handling a rapid rise in P-[Na+] are discussed. The risk of overcorrection is associated with the mechanisms that cause hyponatraemia. Traditional classifications according to volume status are notoriously difficult to handle in clinical practice. Moreover, multiple combined mechanisms are common. More than one mechanism must therefore be considered for safe and lasting correction. Hypernatraemia is less common than hyponatraemia, but implies that the patient is more ill and has a worse prognosis. A practical approach includes treatment of the underlying diseases and restoration of the distorted water and salt balances. Multiple combined mechanisms are common and must be searched for. Importantly, hypernatraemia is not only a matter of water deficit, and treatment of the critically ill patient with an accumulated fluid balance of 20 litres and corresponding weight gain should not comprise more water, but measures to invoke a negative cation balance. Reduction of hypernatraemia/hypertonicity is critical, but should not exceed 12 mmol/l/day in order to reduce the risk of rebounding brain oedema.Critical care (London, England) 02/2013; 17(1):206. DOI:10.1186/cc11805
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- "Recently, it was demonstrated that the V2R may be affected by gain of function mutations that cause a new syndrome: the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) . This phenomenon has been observed for other G-protein-coupled receptors, for example, TSH (thyrotoxicosis), LH (familial male-limited precocious puberty), PTH-rp (Bloom syndrome), and the calcium sensing receptors (hypercalciuric hypocalcemia). "
ABSTRACT: Mutations in the vasopressin V2 receptor gene are responsible for two human tubular disorders: X-linked congenital nephrogenic diabetes insipidus, due to a loss of function of the mutant V2 receptor, and the nephrogenic syndrome of inappropriate antidiuresis, due to a constitutive activation of the mutant V2 receptor. This latter recently described disease may be diagnosed from infancy to adulthood, as some carriers remain asymptomatic for many years. Symptomatic children, however, typically present with clinical and biological features suggesting inappropriate antidiuretic hormone secretion with severe hyponatremia and high urine osmolality, but a low plasma arginine vasopressin level. To date, only two missense mutations in the vasopressin V2 receptor gene have been found in the reported patients. The pathophysiology of the disease requires fuller elucidation as the phenotypic variability observed in patients bearing the same mutations remains unexplained. The treatment is mainly preventive with fluid restriction, but urea may also be proposed.International Journal of Pediatrics 02/2012; 2012:937175. DOI:10.1155/2012/937175