Helbert Rondon-Berrios

Hyponatremia: pathophysiology, classification, manifestations and management.

Hyponatremia has complex pathophysiology, is frequent and has potentially severe clinical manifestations, and its treatment is associated with high risks. Hyponatremia can be hypertonic, isotonic or hypotonic. Hypotonic hyponatremia has multiple etiologies, but only two general mechanisms of development, defective water excretion, usually because of elevated serum vasopressin levels, or excessive fluid intake. The acute treatment of symptomatic hypotonic hyponatremia requires understanding of its targets and risks and requires continuous monitoring of the patient’s clinical status and relevant serum biochemical values. The principles of fluid restriction, which is the mainstay of management of all types of hypotonic hyponatremia, should be clearly understood and followed. Treatment methods specific to various categories of hyponatremia are available. The indications and risks of these treatments should also be well understood. Rapid correction of chronic hypotonic hyponatremia may lead to osmotic demyelination syndrome, which has severe clinical manifestations, and may lead to permanent neurological disability or death. Prevention of this syndrome should be a prime concern of the treatment of hypotonic hyponatremia.

Mild Chronic Hyponatremia in the Ambulatory Setting: Significance and Management

Mild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.

Sodium Retention and Volume Expansion in Nephrotic Syndrome: Implications for Hypertension

Sodium retention is a major clinical feature of nephrotic syndrome. The mechanisms responsible for sodium retention in this setting have been a subject of debate for years. Excessive sodium retention occurs in some individuals with nephrotic syndrome in the absence of activation of the renin-angiotensin-aldosterone system, suggesting an intrinsic defect in sodium excretion by the kidney. Recent studies have provided new insights regarding mechanisms by which sodium transporters are activated by factors present in nephrotic urine. These mechanisms likely have a role in the development of hypertension in nephrotic syndrome, where hypertension may be difficult to control, and provide new therapeutic options for the management of blood pressure and edema in the setting of nephrotic syndrome.

Hypertonicity: Clinical entities, manifestations and treatment

Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium deficit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration, which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level.

Vasopressin receptor antagonists: Characteristics and clinical role

Hyponatremia, the most common electrolyte disorder in hospitalized patients is associated with increased risk of mortality even when mild and apparently asymptomatic. Likewise morbidity manifested as attention deficits, gait disturbances, falls, fractures, and osteoporosis is more prevalent in hyponatremic subjects. Hyponatremia also generates a significant financial burden. Therefore, it is important to explore approaches that effectively and safely treat hyponatremia. Currently available strategies are physiologically sound and affordable but lack evidence from clinical trials and are limited by variable efficacy, slow response, and/or poor compliance. The recent emergence of vasopressin receptor antagonists provides a class of drugs that target the primary pathophysiological mechanism, namely vasopressin mediated impairment of free water excretion. This review summarizes the historical development, pharmacology, clinical trials supporting efficacy and safety, shortcomings, as well as practical suggestions for the use of vasopressin receptor antagonists.

Indices of Serum Tonicity in Clinical Practice

Abstract:Although disturbances of serum tonicity (effective osmolality) may have dire consequences, only surrogate indices of tonicity are available in practice. This report identifies the appropriate index for expressing clinical states of dystonicity. Serum sodium concentration ([Na]S) and osmolality ([Osm]S) may be incongruent. When the tonicity state shown by [Osm]S is higher than [Na]S and the difference between the 2 indices is caused by an excess of solute that distributes in total body water, tonicity is described by [Na]S. When this difference results from a gain of solute with extracellular distribution like mannitol or a decrease in serum water content, causing a falsely low measurement of [Na]S, [Osm]S accurately reflects tonicity. Two indices of tonicity are applicable during hyperglycemia: the tonicity formula (2·[Na]S + [Glucose]S/18) and the corrected [Na]S ([Na]S corrected to a normal [Glucose]S using an empirically derived coefficient). Clinicians should understand the uses and limitations of the tonicity indices.

Vasopressin Receptor Antagonists in Hyponatremia: Uses and Misuses

Decreases in the concentration of sodium in plasma constitute hyponatremia, the commonest electrolyte disorder in clinical medicine. It is now well established that its presence conveys an increased mortality risk even when the decrement is mild. In addition, recent evidence suggests that chronic and apparently asymptomatic hyponatremia is associated with increased morbidity including neurocognitive deficits and bone fractures. Furthermore, hyponatremia is associated with higher health care-related expenses. Consequently, exploring new therapeutic strategies that increase plasma sodium in a safe and effective manner is of paramount importance. In this regard, there are scant data to support the use of traditional management strategies for hyponatremia (fluid restriction, salt tablets, loop diuretics, and normal saline). Furthermore, data from a large hyponatremia registry reveal the limited efficacy of these therapies. More recently vasopressin receptor antagonists provide a promising treatment for hyponatremia by targeting its most common mechanism, namely, increased vasopressin activity. However, uncertainty still lingers as to the optimal indications for the use of vasopressin receptor antagonists in hyponatremia and a few reports have described complications resulting from their misuse. This review summarizes the appropriate and inappropriate uses of vasopressin receptor antagonists in the treatment of hyponatremia.

Applying effective teaching and learning techniques to nephrology education

The interest in nephrology as a career has declined over the last several years. Some of the reasons cited for this decline include the complexity of the specialty, poor mentoring and inadequate teaching of nephrology from medical school through residency. The purpose of this article is to introduce the reader to advances in the science of adult learning, illustrate best teaching practices in medical education that can be extrapolated to nephrology and introduce the basic teaching methods that can be used on the wards, in clinics and in the classroom.

Can Muscle-Kidney Crosstalk Slow Progression of CKD?

Crosstalk refers to interactions between organs or cellular signal transduction pathways and how they influence the function of the target organ or cells. Over decades, nephrologists have developed familiarity with this phenomenon because disorders such as the hepatorenal or cardiorenal syndromes or

Hypertonicity: Pathophysiologic Concept and Experimental Studies

Disturbances in tonicity (effective osmolarity) are the major clinical disorders affecting cell volume. Cell shrinking secondary to hypertonicity causes severe clinical manifestations and even death. Quantitative management of hypertonic disorders is based on formulas computing the volume of hypotonic fluids required to correct a given level of hypertonicity. These formulas have limitations. The major limitation of the predictive formulas is that they represent closed system calculations and have been tested in anuric animals. Consequently, the formulas do not account for ongoing fluid losses during development or treatment of the hypertonic disorders. In addition, early comparisons of serum osmolality changes predicted by these formulas and observed in animals infused with hypertonic solutions clearly demonstrated that hypertonicity creates new intracellular solutes causing rises in serum osmolality higher than those predicted by the formulas. The mechanisms and types of intracellular solutes generated by hypertonicity and the effects of the solutes have been studied extensively in recent times. The solutes accumulated intracellularly in hypertonic states have potentially major adverse effects on the outcomes of treatment of these states. When hypertonicity was produced by the infusion of hypertonic sodium chloride solutions, the predicted and observed changes in serum sodium concentration were equal. This finding justifies the use of the predictive formulas in the management of hypernatremic states.