Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United ...States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status. Recently identified parameters, including fractional uric acid excretion and plasma copeptin concentration, may further improve the diagnostic approach. The treatment for hyponatremia is chosen on the basis of duration and symptoms. For acute or severely symptomatic hyponatremia, both guidelines adopted the approach of giving a bolus of hypertonic saline. Although fluid restriction remains the first-line treatment for most forms of chronic hyponatremia, therapy to increase renal free water excretion is often necessary. Vasopressin receptor antagonists, urea, and loop diuretics serve this purpose, but received different recommendations in the two guidelines. Such discrepancies may relate to different interpretations of the limited evidence or differences in guideline methodology. Nevertheless, the development of guidelines has been important in advancing this evolving field.
Extracellular vesicles have been isolated in various body fluids, including urine. The cargo of urinary extracellular vesicles (uEVs) is composed of proteins and nucleic acids reflecting the ...physiological and possibly pathophysiological state of cells lining the nephron. Because urine is a noninvasive and readily available biofluid, the discovery of uEVs has opened a new field of biomarker research. Their potential use as diagnostic, prognostic, or therapeutic biomarkers for various kidney diseases, including glomerulonephritis, acute kidney injury, tubular disorders, and polycystic kidney disease, is currently being explored. Some challenges, however, remain. These challenges include the need to standardize isolation methods, normalization between samples, and validation of candidate biomarkers. Also, the development of a high-throughput platform to isolate and analyze uEVs, for example, an enzyme-linked immunosorbent assay, is desirable. Here, we review recent studies on uEVs dealing with kidney physiology and pathophysiology. Furthermore, we discuss new and exciting developments regarding vesicles, including their role in cell-to-cell communication and the possibility of using vesicles as a therapy for kidney disorders.
Daily dietary potassium (K
) intake may be as large as the extracellular K
pool. To avoid acute hyperkalemia, rapid removal of K
from the extracellular space is essential. This is achieved by ...translocating K
into cells and increasing urinary K
excretion. Emerging data now indicate that the renal thiazide-sensitive NaCl cotransporter (NCC) is critically involved in this homeostatic kaliuretic response. This suggests that the early distal convoluted tubule (DCT) is a K
sensor that can modify sodium (Na
) delivery to downstream segments to promote or limit K
secretion. K
sensing is mediated by the basolateral K
channels Kir4.1/5.1, a capacity that the DCT likely shares with other nephron segments. Thus, next to K
-induced aldosterone secretion, K
sensing by renal epithelial cells represents a second feedback mechanism to control K
balance. NCC's role in K
homeostasis has both physiological and pathophysiological implications. During hypovolemia, NCC activation by the renin-angiotensin system stimulates Na
reabsorption while preventing K
secretion. Conversely, NCC inactivation by high dietary K
intake maximizes kaliuresis and limits Na
retention, despite high aldosterone levels. NCC activation by a low-K
diet contributes to salt-sensitive hypertension. K
-induced natriuresis through NCC offers a novel explanation for the antihypertensive effects of a high-K
diet. A possible role for K
in chronic kidney disease is also emerging, as epidemiological data reveal associations between higher urinary K
excretion and improved renal outcomes. This comprehensive review will embed these novel insights on NCC regulation into existing concepts of K
homeostasis in health and disease.
The topic of intravenous (IV) fluids may be regarded as “reverse nephrology”, because nephrologists usually treat to remove fluids rather than to infuse them. However, because nephrology is deeply ...rooted in fluid, electrolyte, and acid-base balance, IV fluids belong in the realm of our specialty. The field of IV fluid therapy is in motion due to the increasing use of balanced crystalloids, partly fueled by the advent of new solutions. This review aims to capture these recent developments by critically evaluating the current evidence base. It will review both indications and complications of IV fluid therapy, including the characteristics of the currently available solutions. It will also cover the use of IV fluids in specific settings such as kidney transplantation and pediatrics. Finally, this review will address the pathogenesis of saline-induced hyperchloremic acidosis, its potential effect on outcomes, and the question if this should lead to a definitive switch to balanced solutions.
Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum ...of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-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 the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.
Abstract Background Electrolyte disorders have been studied mainly in hospitalized patients, whereas data in the general population are limited. The aim of this study was to determine the prevalence ...and risk factors of common electrolyte disorders in older subjects recruited from the general population. Methods A total of 5179 subjects aged 55 years or more were included from the population-based Rotterdam Study. We focused on hyponatremia, hypernatremia, hypokalemia, hyperkalemia, and hypomagnesemia. Multivariable logistic regression was used to study potential associations with renal function, comorbidity, and medication. The adjusted mortality also was determined for each electrolyte disorder. Results A total of 776 subjects (15.0%) had at least 1 electrolyte disorder, with hyponatremia (7.7%) and hypernatremia (3.4%) being most common. Diabetes mellitus was identified as an independent risk factor for hyponatremia and hypomagnesemia, whereas hypertension was associated with hypokalemia. Diuretics were independently associated with several electrolyte disorders: thiazide diuretics (hyponatremia, hypokalemia, hypomagnesemia), loop diuretics (hypernatremia, hypokalemia), and potassium-sparing diuretics (hyponatremia). The use of benzodiazepines also was associated with hyponatremia. Hyponatremic subjects who used both thiazides and benzodiazepines had a 3 mmol/L lower serum sodium concentration than subjects using 1 or none of these drugs ( P < .001). Hyponatremia and hypomagnesemia were independently associated with an increased mortality risk. Conclusions Electrolyte disorders are common among older community subjects and mainly associated with diabetes mellitus and diuretics. Subjects who used both thiazides and benzodiazepines had a more severe degree of hyponatremia. Because even mild electrolyte disorders were associated with mortality, monitoring of electrolytes and discontinuation of offending drugs may improve outcomes.
Individuals with CKD are at a higher risk of cardiovascular morbidity and mortality. Acidosis is positively correlated with CKD progression and elevated systolic BP. Sodium bicarbonate is an ...efficacious treatment of acidosis, although this may also increase systolic BP. In this systematic review and meta-analysis, we summarize the evidence evaluating systolic BP and antihypertensive medication change (which may indicate systolic BP change) in response to sodium bicarbonate therapy in individuals with CKD.
Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) trials registry databases were searched for randomized control trials where sodium bicarbonate was compared with placebo/usual care in CKD stage G1-5 non-dialysis-dependent populations. Random effects meta-analyses were used to evaluate changes in systolic BP and BP-modifying drugs after sodium bicarbonate intervention.
Fourteen randomized control trials (2110 individuals, median follow-up 27 interquartile range 97 weeks, mean age 60 SD 10 years, mean systolic BP 136 SD 17 mm Hg, mean eGFR 38 SD 10 ml/min, mean serum bicarbonate 22 SD 4 mmol/L) were eligible for inclusion. Meta-analysis suggested that sodium bicarbonate did not influence systolic BP in individuals with CKD stage G1-5. Results were consistent when stratifying by dose of sodium bicarbonate or duration of intervention. Similarly, there was no significant increase in the use of antihypertensive medication or diuretics in individuals taking sodium bicarbonate, whereas there was a greater decrease in antihypertensive medication use in individuals taking sodium bicarbonate compared with controls.
Our results suggest, with moderate certainty, that sodium bicarbonate supplementation does not adversely affect systolic BP in CKD or negatively influence antihypertensive medication requirements.
Diuretic Resistance Hoorn, Ewout J., MD, PhD; Ellison, David H., MD
American journal of kidney diseases,
01/2017, Letnik:
69, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in edema despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug ...therapy or dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption in nephron sites that are not blocked by the diuretic. To illustrate the pathophysiology and management of diuretic resistance, we describe a patient with nephrotic syndrome. This patient presented with generalized pitting edema and weight gain despite the use of oral loop diuretics. Nephrotic syndrome may cause mucosal edema of the intestine, limiting the absorption of diuretics. In addition, the patient’s kidney function had deteriorated, impairing the tubular secretion of diuretics. He was admitted for intravenous loop diuretic treatment. However, this was ineffective, likely due to compensatory sodium reabsorption by other tubular segments. The combination of loop diuretics with triamterene, a blocker of the epithelial sodium channel, effectively reduced body weight and edema. Recent data suggest that plasmin in nephrotic urine can activate the epithelial sodium channel, potentially contributing to the diuretic resistance in this patient. This case is used to illustrate and review the mechanisms of, and possible interventions for, diuretic resistance.
Acute hyponatremia can cause death if cerebral edema is not treated promptly. Conversely, if chronic hyponatremia is corrected too rapidly, osmotic demyelination may ensue, which also potentially is ...lethal. However, these severe complications of hyponatremia are relatively uncommon and often preventable. More commonly, hyponatremia predicts mortality in patients with advanced heart failure or liver cirrhosis. In these conditions, it generally is assumed that hyponatremia reflects the severity of the underlying disease rather than contributing directly to mortality. The same assumption holds for the recently reported associations between hyponatremia and mortality in patients with pulmonary embolism, pulmonary hypertension, pneumonia, and myocardial infarction. However, recent data suggest that chronic and mild hyponatremia in the general population also are associated with mortality. In addition, hyponatremia has been associated with mortality in long-term hemodialysis patients without residual function in whom the underlying disease cannot be responsible for hyponatremia. These new data raise the question of whether hyponatremia by itself can contribute to mortality or it remains a surrogate marker for other unknown risk factors. We review hyponatremia and mortality and explore the possibility that hyponatremia perturbs normal physiology in the absence of cerebral edema or osmotic demyelination.
For years, hypotonic polyuria was assessed with the water-deprivation test, with subsequent measurements of plasma vasopressin (the direct test) or urine osmolality (the indirect test).2 Depending on ...the underlying disorder, water deprivation should increase plasma vasopressin and urine osmolality (primary polydipsia), increase only plasma vasopressin (nephrogenic diabetes insipidus), or increase neither plasma vasopressin nor urine osmolality (central diabetes insipidus). Winzeler and colleagues used their new arginine stimulation test in a development cohort and a validation cohort of patients with central diabetes insipidus (21 in development cohort, 17 in validation cohort) or primary polydipsia (31 in development cohort, 27 in validation cohort) and a cohort of healthy adults (20 in development cohort, 30 validation cohort) and children (who had suspected growth hormone deficiency; 42 in development cohort).6 As predicted, arginine increased copeptin concentrations 1·8–2·2 times in patients with primary polydipsia and the cohort of healthy adults and children, but only by 1·2 times in the patients with central diabetes insipidus. Patients on chronic desmopressin treatment sometimes have hyponatraemia10 that can suppress endogenous vasopressin synthesis,11 which might blunt the response to arginine. ...whether the arginine stimulation test would reach the same diagnostic accuracy in a cohort of patients with unexplained hypotonic polyuria is unclear.
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