Hypertension and pregnancy-related hypertension are major public health problems of largely unknown causes. We describe a mutation in the mineralocorticoid receptor (MR), S810L, that causes early-onset hypertension that is markedly exacerbated in pregnancy. This mutation results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups, normally MR antagonists, becoming potent agonists. Structural and biochemical studies indicate that the mutation results in the gain of a van der Waals interaction between helix 5 and helix 3 that substitutes for interaction of the steroid 21-hydroxyl group with helix 3 in the wild-type receptor. This helix 5-helix 3 interaction is highly conserved among diverse nuclear hormone receptors, suggesting its general role in receptor activation.

The administration of isotonic saline in maintenance parenteral fluids is the most important prophylactic measure that can be taken to prevent the development of hyponatremia in children who receive parenteral fluids.

Quantitative PCR for BKV is a sensitive and reliable method for following the course of the infection in renal transplant patients. In addition, cidofovir therapy may be useful in the treatment of some of these patients, and its role needs to be investigated further.

SUBCOMMITTEE ON FLUID AND ELECTROLYTE THERAPY Maintenance intravenous fluids (IVFs) are used to provide critical supportive care for children who are acutely ill. IVFs are required if sufficient fluids cannot be provided by using enteral administration for reasons such as gastrointestinal illness, respiratory compromise, neurologic impairment, a perioperative state, or being moribund from an acute or chronic illness. Despite the common use of maintenance IVFs, there is high variability in fluid prescribing practices and a lack of guidelines for fluid composition administration and electrolyte monitoring. The administration of hypotonic IVFs has been the standard in pediatrics. Concerns have been raised that this approach results in a high incidence of hyponatremia and that isotonic IVFs could prevent the development of hyponatremia. Our goal in this guideline is to provide an evidence-based approach for choosing the tonicity of maintenance IVFs in most patients from 28 days to 18 years of age who require maintenance IVFs. This guideline applies to children in surgical (postoperative) and medical acute-care settings, including critical care and the general inpatient ward. Patients with neurosurgical disorders, congenital or acquired cardiac disease, hepatic disease, cancer, renal dysfunction, diabetes insipidus, voluminous watery diarrhea, or severe burns; neonates who are younger than 28 days old or in the NICU; and adolescents older than 18 years old are excluded. We specifically address the tonicity of maintenance IVFs in children. The Key Action Statement of the subcommittee is as follows: 1A: The American Academy of Pediatrics recommends that patients 28 days to 18 years of age requiring maintenance IVFs should receive isotonic solutions with appropriate potassium chloride and dextrose because they significantly decrease the risk of developing hyponatremia (evidence quality: A; recommendation strength: strong)

A critical aspect of the care of acutely ill patients is the administration of intravenous fluids. Intravenous fluids may be required as a bolus infusion for resuscitation or as a continuous infusion when sufficient fluids cannot be ingested orally.The goal of maintenance intravenous fluids is to preserve the extracellular volume while maintaining a normal electrolyte balance. An appropriate maintenance fluid provides an adequate quantity of both water and electrolytes to ensure good tissue perfusion without causing complications related to fluid overload or volume depletion. It also prevents the development of hyponatremia, hypernatremia, and other electrolyte imbalances.Despite the almost ubiquitous need for intravenous fluids in acutely ill patients, there has been little consensus on the most appropriate rate of administration and composition of intravenous fluids, and practice patterns with respect to maintenance fluids vary widely. 1-3 In addition, acutely ill patients frequently have conditions that impair normal water and electrolyte homeostasis (Table 1), and choosing the appropriate volume and composition of intravenous fluids requires great care. 4 Intravenous fluids can be classified, according to the concentration of sodium plus potassium in the fluid, as being either isotonic (approximately equal to the plasma sodium concentration) or hypotonic (less than the plasma sodium concentration). The dextrose content of intravenous fluids has no effect on the tonicity, since the dextrose is rapidly metabolized when it enters the bloodstream and should not produce hyperglycemia.A prevailing practice has been to administer hypotonic maintenance intravenous fluids in both children and adults. 1,5,6 This practice has been associated with a high incidence of hospital-acquired hyponatremia and more than 100 reports of iatrogenic deaths or permanent neurologic impairment related to hyponatremic encephalopathy, 7-11 since acutely ill patients may have disease states associated with an excess of arginine vasopressin (AVP) (Fig. 1). This excess impairs excretion of free water and may aggravate hyponatremia. 15,16 Over the past decade, many studies have evaluated the association between the composition and quantity of maintenance fluids and the development of hyponatremia. Recent data also suggest that rapid volume expansion with 0.9% saline (normal saline), as compared with balanced electrolyte solutions, may result in untoward complications. 17 The current review considers the physiological principles that guide the appropriate selection of intravenous fluids, as well as the recent literature evaluating the safety of various intravenous fluids with respect to their composition and rate of administration.

Dysnatremias are among the most common electrolyte abnormalities encountered in hospitalized patients. In most cases, a dysnatremia results from improper fluid management. Dysnatremias can occasionally result in death or permanent neurological damage, a tragic complication that is usually preventable. In this manuscript, we discuss the epidemiology, pathogenesis and prevention and treatment of dysnatremias in children. We report on over 50 patients who have suffered death or neurological injury from hospital-acquired hyponatremia. The main factor contributing to hyponatremic encephalopathy in children is the routine use of hypotonic fluids in patients who have an impaired ability to excrete free-water, due to such causes as the postoperative state, volume depletion and pulmonary and central nervous system diseases. The appropriate use of 0.9% sodium chloride in parenteral fluids would likely prevent most cases of hospital-acquired hyponatremic encephalopathy. We report on 15 prospective studies in over 500 surgical patients that demonstrate that normal saline effectively prevents postoperative hyponatremia, and hypotonic fluids consistently result in a fall in serum sodium. Hyponatremic encephalopathy is a medical emergency that should be treated with hypertonic saline, and should never be managed with fluid restriction alone. Hospital-acquired hypernatremia occurs in patients who have restricted access to fluids in combination with ongoing free-water losses. Hypernatremia could largely be prevented by providing adequate free-water to patients who have ongoing free-water losses or when mild hypernatremia (Na>145 mE/l) develops. A group at high-risk for neurological damage from hypernatremia in the outpatient setting is that of the breastfed infant. Breastfed infants must be monitored closely for insufficient lactation and receive lactation support. Judicious use of infant formula supplementation may be called for until problems with lactation can be corrected.

SummaryBackground and objectives This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.Design, setting, participants, & measurements A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA. Questionnaires were administered to evaluate the clinical and laboratory data.Results Homozygous deletion in CFHR1 was detected in 32% of the patients with aHUS tested, compared with 2.5% of controls (P,0.001). CFH antibodies were present in 25% of the patients and none of the controls. CFH antibodies were detected in 82% of patients with homozygous CFHR1 gene deletion and in 6% of patients without. CFH antibody-positive patients with aHUS showed a significantly lower platelet nadir at disease onset and significantly less frequent involvement of the central nervous system than did antibody-negative patients. Antibody-positive patients also received plasma therapy more often.Conclusion Homozygous deletion in CFHR1 is strongly associated with occurrence of CFH antibodies in pediatric patients with aHUS. However, despite this apparent genetic disease predisposition, it cannot be considered an exclusive cause for aHUS. Initial presentation of Shiga toxin-negative HUS with severe thrombocytopenia and no central nervous system complications in pediatric patients is especially suspicious for CFH antibody aHUS.

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP).