Classification of Uremic Toxins and Their Role in Kidney Failure.

Advances in our understanding of uremic retention solutes, and improvements in hemodialysis membranes and other techniques designed to remove uremic retention solutes, offer opportunities to readdress the definition and classification of uremic toxins. A consensus conference was held to develop recommendations for an updated definition and classification scheme on the basis of a holistic approach that incorporates physicochemical characteristics and dialytic removal patterns of uremic retention solutes and their linkage to clinical symptoms and outcomes. The major focus is on the removal of uremic retention solutes by hemodialysis. The identification of representative biomarkers for different classes of uremic retention solutes and their correlation to clinical symptoms and outcomes may facilitate personalized and targeted dialysis prescriptions to improve quality of life, morbidity, and mortality. Recommendations for areas of future research were also formulated, aimed at improving understanding of uremic solutes and improving outcomes in patients with CKD.

Ferumoxytol for the treatment of iron deficiency anemia.

INTRODUCTION: Ferumoxytol is a superparamagnetic molecule originally developed as a contrast agent for magnetic resonance imaging. Elemental iron is contained within the carbohydrate core and is released slowly after infusion allowing a large dose of iron to be administered in a short period of time. Ferumoxytol, originally approved for iron deficiency in chronic kidney disease, received a broad label for any cause of iron deficiency after oral iron intolerance or in those circumstances when oral iron is ineffective or harmful. Areas covered: The chemistry, pharmacology and pharmacokinetics of ferumoxytol were reviewed. Retrospective, observational, and prospective phase II and III trials were reviewed. When appropriate, comparative safety and efficacy parameters were reported. Differentiation between minor infusion reactions and more severe hypersensitivity reactions that may lead to anaphylaxis is described. Expert commentary: Ferumoxytol is a safe and effective iron formulation providing a means of iron repletion in persons with iron deficiency with or without anemia. Relative to iron sucrose, ferric gluconate, and iron dextran and similar to ferric carboxymaltose and iron isomaltoside, ferumoxytol yields relatively low quantities of labile free iron. Hypersensitivity and anaphylaxis is extremely rare. Hypophosphatemia with ferumoxytol's administration is extremely rare. Optimal strategies for application of ferumoxytol-enhanced imaging and full replacement dosing in a single setting remain to be determined.

Nephrotoxicity and Chinese Herbal Medicine.

Chinese herbal medicine has been practiced for the prevention, treatment, and cure of diseases for thousands of years. Herbal medicine involves the use of natural compounds, which have relatively complex active ingredients with varying degrees of side effects. Some of these herbal medicines are known to cause nephrotoxicity, which can be overlooked by physicians and patients due to the belief that herbal medications are innocuous. Some of the nephrotoxic components from herbs are aristolochic acids and other plant alkaloids. In addition, anthraquinones, flavonoids, and glycosides from herbs also are known to cause kidney toxicity. The kidney manifestations of nephrotoxicity associated with herbal medicine include acute kidney injury, CKD, nephrolithiasis, rhabdomyolysis, Fanconi syndrome, and urothelial carcinoma. Several factors contribute to the nephrotoxicity of herbal medicines, including the intrinsic toxicity of herbs, incorrect processing or storage, adulteration, contamination by heavy metals, incorrect dosing, and interactions between herbal medicines and medications. The exact incidence of kidney injury due to nephrotoxic herbal medicine is not known. However, clinicians should consider herbal medicine use in patients with unexplained AKI or progressive CKD. In addition, exposure to herbal medicine containing aristolochic acid may increase risk for future uroepithelial cancers, and patients require appropriate postexposure screening.

Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia: 2014 update.

Exercise-associated hyponatremia (EAH) is defined by a serum or plasma sodium concentration below the normal reference range of 135 mmol/L that occurs during or up to 24 hours after prolonged physical activity. It is reported to occur in individual physical activities or during organized endurance events conducted in austere environments in which medical care is limited and often not available, and patient evacuation to definitive care is often greatly delayed. Rapid recognition and appropriate treatment are essential in the severe form to ensure a positive outcome. Failure in this regard is a recognized cause of event-related fatality. In an effort to produce best practice guidelines for EAH in the austere environment, the Wilderness Medical Society convened an expert panel. The panel was charged with the development of evidence-based guidelines for management of EAH. Recommendations are made regarding the situations when sodium concentration can be assessed in the field and when these values are not known. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. This is an updated version of the original WMS Practice Guidelines for Treatment of Exercise-Associated Hyponatremia published in Wilderness & Environmental Medicine 2013;24(3):228-240.

Wilderness Medical Society practice guidelines for treatment of exercise-associated hyponatremia.

Exercise-associated hyponatremia (EAH) typically occurs during or up to 24 hours after prolonged physical activity, and is defined by a serum or plasma sodium concentration below the normal reference range of 135 mEq/L. It is also reported to occur in individual physical activities or during organized endurance events conducted in austere environments in which medical care is limited or often not available, and patient evacuation to definitive care is often greatly delayed. Rapid recognition and appropriate treatment are essential in the severe form to ensure a positive outcome. Failure in this regard is a recognized cause of event-related fatality. In an effort to produce best practice guidelines for EAH in the austere environment, the Wilderness Medical Society convened an expert panel. The panel was charged with the development of evidence-based guidelines for management of EAH. Recommendations are made regarding the situations when sodium concentration can be assessed in the field and when these values are not known. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians.

The role of therapeutic plasma exchange in poisonings and intoxications.

Poisonings, intoxications, and drug overdoses are common occurrences and rapid lowering of the toxin level is a cornerstone of all effective therapies. Therapeutic plasma exchange (TPE) has several unique characteristics that allow it to be a potentially effective therapy in rapidly achieving this goal. Specifically, TPE allows for the removal of large molecular weight, protein-bound molecules that have a small volume of distribution. Due to the nature of poisonings, intoxications, and drug overdoses, no randomized controlled trials studying the efficacy of TPE in these situations exist. Thus, careful interpretation and analysis of case reports and series are required to assess the potential efficacy of this therapy. Recent data suggest that TPE may also be effective in the therapy of patients receiving biologic treatments who develop life-threatening complications due to therapy.

Ferumoxytol for the treatment of iron deficiency.

Intravenous iron is standard for dialysis-associated anemia and its use is rising dramatically in other settings. Except for the dextrans, full iron replacement requires multiple visits. Nonetheless, safety concerns abound. Ferumoxytol, a recently approved modified dextran with a carbohydrate core that tightly binds the iron moiety, decreasing free iron and ostensibly increasing safety, was approved by the US FDA, in June 2009, for the treatment of iron deficiency associated with chronic kidney disease and end-stage renal disease. This formulation, uniquely, can be administered in a large dose as a short intravenous injection of 1 min or less, markedly facilitating care. Recent post-marketing safety issues have been raised resulting in a change in the package insert. This article examines existing clinical data and posits reasons for the labeling change. Potential future use of this formulation is opined.

Variability in calcium, phosphorus, and parathyroid hormone in patients on hemodialysis.

Calcium, phosphorus, and parathyroid hormone (PTH) levels are routinely measured in patients undergoing chronic hemodialysis. Medications, diet, and dialytic therapies are modified based upon these lab values to achieve specific goal values in the hope of improving outcomes. However, the variability of these values in patients undergoing chronic hemodialysis has only been rarely studied. We prospectively investigated the variability of these measures in 35 patients undergoing chronic hemodialysis as well as the impact of this variability on clinical decision-making in a prospective manner over a month. There is significant session-to-session variability in phosphorus and PTH values (mean coefficient of variations [CV] of 0.19 and 0.31, respectively). Calcium variability is much lower (mean CV of 0.05). Not surprisingly, the CV for all values is increased during the long interdialytic interval. The impact of this variability on clinical decision-making was analyzed. The variability in calcium, phosphorus, and PTH values would lead to a different clinical decision in 23.6%, 41.2%, and 39.7% of different session lab values. We also investigated the variability of these lab measures over a year in these patients and found that the session-to-session variability was very similar to the month-to-month variability. The high degree of variability of these parameters has important implications for clinical decision-making and for implementation of pay-for-performance measures.

Ferumoxytol for the treatment of anemia in chronic kidney disease.

Iron deficiency anemia is a common occurrence in patients with chronic kidney disease and many patients do not respond well to supplementation with oral iron. There are now five intravenous iron preparations available for use in the chronic kidney disease patient, with ferumoxytol being the most recently approved agent. As opposed to previously available intravenous irons, ferumoxytol has the advantage of not needing a test dose, allowing a large dose of iron (510 mg) to be given in a short period of time by bolus injection, and no reported cases of anaphylaxis. Ferumoxytol has advantages for use in the outpatient setting to treat iron deficiency, in patients with chronic kidney disease not yet on dialysis and in patients on peritoneal dialysis. The use of ferumoxytol in the hemodialysis population where thrice weekly intravenous access is the norm is less clear. Cost-effectiveness studies and post-approval studies on ferumoxytol as well as changes in the cost structure of dialysis reimbursement will likely have a large impact on the use of this new agent.