Hyperkalemia treatment standard.

Hyperkalemia is a common electrolyte disturbance in both inpatient and outpatient clinical practice. The severity and associated risk depends on the underlying cause and rate of potassium (K+) increase. Acute hyperkalemia requires immediate attention due to potentially life-threatening manifestations resulting from the rapid increase in plasma K+ concentration. Treatment is initially focused on stabilizing the cardiac membrane, followed by maneuvers to shift K+ into the cells, and ultimately initiating strategies to decrease total body K+ content. Chronic hyperkalemia develops over a more extended period of time and manifestations tend to be less severe. Nevertheless, the disorder is not benign since chronic hyperkalemia is associated with increased morbidity and mortality. The approach to patients with chronic hyperkalemia begins with a review of medications potentially responsible for the disorder, ensuring effective diuretic therapy and correcting metabolic acidosis if present. The practice of restricting foods high in K+ to manage hyperkalemia is being reassessed since the evidence supporting the effectiveness of this strategy is lacking. Rather, dietary restriction should be more nuanced, focusing on reducing the intake of nonplant sources of K+. Down-titration and/or discontinuation of renin-angiotensin-aldosterone inhibitors should be discouraged since these drugs improve outcomes in patients with heart failure and proteinuric kidney disease. In addition to other conservative measures, K+ binding drugs and sodium-glucose cotransporter 2 inhibitors can assist in maintaining the use of these drugs.

Respiratory Acidosis and Respiratory Alkalosis: Core Curriculum 2023.

The respiratory system plays an integral part in maintaining acid-base homeostasis. Normal ventilation participates in the maintenance of an open buffer system, allowing for excretion of CO2 produced from the interaction of nonvolatile acids and bicarbonate. Quantitatively of much greater importance is the excretion of CO2 derived from volatile acids produced from the complete oxidation of fat and carbohydrate. A primary increase in CO2 tension of body fluids is the cause of respiratory acidosis and develops most commonly from one or more of the following: (1) disorders affecting gas exchange across the pulmonary capillary, (2) disorders of the chest wall and the respiratory muscles, and/or (3) inhibition of the medullary respiratory center. Respiratory alkalosis or primary hypocapnia is most commonly caused by disorders that increase alveolar ventilation and is defined by an arterial partial pressure of CO2 <35 mm Hg with subsequent alkalization of body fluids. Both disorders can lead to life-threatening complications, making it of paramount importance for the clinician to have a thorough understanding of the cause and treatment of these acid-base disturbances.

Change in albuminuria as a surrogate endpoint for cardiovascular and renal outcomes in patients with diabetes.

For the purpose of predicting clinical outcomes in patients with diabetes and chronic kidney disease, change in albuminuria is a good candidate to be a surrogate marker for future cardiovascular events and progression of kidney disease. Spot urine albumin/creatinine ratio is convenient and recognized as a viable alternative to 24-h albumin, with some limitations. Although there is sufficient evidence to validate its use in clinical trials as a surrogate endpoint for renal outcomes, this is not yet the case for cardiovascular outcomes. While change in albuminuria as a primary or secondary endpoint is trial-specific, its use should be encouraged, nonetheless.

New Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease.

Potassium disorders are one of the most common electrolyte abnormalities in patients with chronic kidney disease (CKD), contributing to poor clinical outcomes. Maintaining serum potassium levels within the physiologically normal range is critically important in these patients. Dietary potassium restriction has long been considered a core strategy for the management of chronic hyperkalemia in patients with CKD. However, this has been challenged by recent evidence suggesting a paradigm shift toward fostering more liberalized, plant-based dietary patterns. The advent of novel potassium binders and an improved understanding of gastrointestinal processes involved in potassium homeostasis (e.g., gastrointestinal potassium wasting) may facilitate a paradigm shift and incorporation of heart-healthy potassium-enriched food sources. Nevertheless, uncertainty regarding the risk-benefit of plant-based diets in the context of potassium management in CKD remains, requiring well-designed clinical trials to determine the efficacy of dietary potassium manipulation toward improvement of clinical outcomes in patients with CKD.

Starvation Ketosis and the Kidney.

BACKGROUND: The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis. SUMMARY: The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO3-. The replacement of urea with NH4+ provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na+ serve to minimize kidney K+ wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. Key Message: Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.

Gastrointestinal potassium binding in hemodialysis.

Hyperkalemia in patients on dialysis is associated with an increased mortality rate. Dietary restriction is often not effective and deprives patients of heart-healthy foods. Lowering the dialysate K+ concentration can potentially increase the risk of arrhythmias. In this commentary, we discuss the findings of Amdur et al., and the potential use for K+-binding drugs as a strategy to maintain plasma K+ concentrations within a narrow and normal range during the interdialytic and intradialytic intervals.

Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Potassium disorders are common in patients with kidney disease, particularly in patients with tubular disorders and low glomerular filtration rate. A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. The issues discussed encompassed our latest understanding of the regulation of tubular potassium excretion in health and disease; the relationship of potassium intake to cardiovascular and kidney outcomes, with increasing evidence showing beneficial associations with plant-based diet and data to suggest a paradigm shift from the idea of dietary restriction toward fostering patterns of eating that are associated with better outcomes; the paucity of data on the effect of dietary modification in restoring abnormal serum potassium to the normal range; a novel diagnostic algorithm for hypokalemia that takes into account the ascendency of the clinical context in determining cause, aligning the educational strategy with a practical approach to diagnosis; and therapeutic approaches in managing hyperkalemia when chronic and in the emergency or hospital ward. In sum, we provide here our conference deliberations on potassium homeostasis in health and disease, guidance for evaluation and management of dyskalemias in the context of kidney diseases, and research priorities in each of the above areas.

Potassium binding for conservative and preservative management of chronic kidney disease.

PURPOSE OF REVIEW: Hyperkalemia is a life-threatening complication of chronic kidney disease (CKD). Risk factors include advanced kidney impairment, diabetes, hypertension, heart failure, and consumption of a K-enriched diet. High-K diets provide health benefits to include reductions in blood pressure, stroke risk, and osteoporosis. Individuals at the highest risk for developing hyperkalemia are those who would benefit most from high K diets. Inhibitors of the renin--angiotensin--aldosterone system (RAASi) are effective in reducing cardiovascular events and slowing the progression of CKD, yet hyperkalemia is a risk factor. Discussed are new strategies facilitating use of both high-K diets and pharmacology to preserve kidney function and reduce cardiovascular events. RECENT FINDINGS: Sodium zirconium cyclosilicate and patiromer are new K-binding drugs approved for the treatment of hyperkalemia. Both are efficacious in the short-term and long-term treatment of hyperkalemia. These binders are effective in treating hyperkalemia while facilitating RAASi therapy. SUMMARY: Hyperkalemia is a life-threatening condition. New K-binding drugs allow for optimal use of pharmacological therapy, such as RAASi, enhancing their cardiorenal protection. Health benefits from consumption of high K foods may also be enhanced by use of these binders. In conclusion, there are new well tolerated and effective K-binding agents for acutely and chronically managing hyperkalemia.

Fluid overload as a therapeutic target for the preservative management of chronic kidney disease.

PURPOSE OF REVIEW: There is growing clinical evidence of adverse effects of fluid overload on kidney outcomes in patients with cardiovascular disease who are not yet receiving kidney replacement therapy. In this review, we discuss the patient populations most at risk for fluid overload, the pathophysiology associated with fluid overload, and finally treatment options. RECENT FINDINGS: The severity of fluid overload is an independent risk factor for both an increased risk of rapidly declining kidney function and increased risk for the need of kidney replacement therapy. High venous pressure within the kidney secondarily causes a decrease in kidney perfusion, which in turn signals salt retention and the resulting increase in plasma volume completes a vicious cycle propagating ongoing kidney injury. Fluid overload has also been identified as a risk factor for the combined outcome of all-cause mortality and cardiovascular morbidity. This increased risk in some studies has been identified as more important than hypertension in predicting both the increased risk of kidney disease progression and morbidity and mortality from cardiovascular disease. Once fluid status is accurately assessed, a combination of salt restriction and effective diuretic therapy is the first-line therapy to manage this complication. In those patients who require additional therapy, use of a V2 receptor antagonists can be considered. Finally, some patients may benefit from peritoneal dialysis to bring about volume removal even if they do not yet require dialysis for uremic complications. SUMMARY: Excess fluid or fluid overload appears to enhance chronic kidney disease progression and its treatment and resolution is a potential disease-modifying intervention.

Let Them Eat Healthy: Can Emerging Potassium Binders Help Overcome Dietary Potassium Restrictions in Chronic Kidney Disease?

Potassium-rich foods might provide many health benefits even to people who have declining renal function. The barrier to obtaining these health benefits has long been the concern over hyperkalemia. There are new and novel treatment options available which may enable patients with chronic kidney disease to obtain the health benefits of eating a diet that contains foods such as fruits and vegetables which are high in potassium while reducing the risk of hyperkalemia. We conclude by emphasizing the need for clinical trials with patients on hemodialysis to directly compare the current standard of care, including a potassium-restricted diet, to a potassium-liberalized diet with a potassium binder. The outcome measures would be serum potassium (<5.3 mmol/L), assessments of acidosis, blood pressure, constipation, glycemic control, overhydration, and azotemia, all of which might change in a favorable direction with vegetarian diets as well as quality of life and satisfaction.

Determinants of body fat distribution in humans may provide insight about obesity-related health risks.

Obesity increases the risks of developing cardiovascular and metabolic diseases and degrades quality of life, ultimately increasing the risk of death. However, not all forms of obesity are equally dangerous: some individuals, despite higher percentages of body fat, are at less risk for certain chronic obesity-related complications. Many open questions remain about why this occurs. Data suggest that the physical location of fat and the overall health of fat dramatically influence disease risk; for example, higher concentrations of visceral relative to subcutaneous adipose tissue are associated with greater metabolic risks. As such, understanding the determinants of the location and health of adipose tissue can provide insight about the pathological consequences of obesity and can begin to outline targets for novel therapeutic approaches to combat the obesity epidemic. Although age and sex hormones clearly play roles in fat distribution and location, much remains unknown about gene regulation at the level of adipose tissue or how genetic variants regulate fat distribution. In this review, we discuss what is known about the determinants of body fat distribution, and we highlight the important roles of sex hormones, aging, and genetic variation in the determination of body fat distribution and its contribution to obesity-related comorbidities.

Physiology and Pathophysiology of Potassium Homeostasis: Core Curriculum 2019.

Total-body potassium (K+) content and appropriate distribution of K+ across the cell membrane is vitally important for normal cellular function. Total-body K+ content is determined by changes in excretion of K+ by the kidneys in response to intake levels. Under normal conditions, insulin and ß-adrenergic tone also make important contributions in maintaining internal distribution of K+. However, despite these homeostatic pathways, disorders of altered K+ homeostasis are common. Appreciating the pathophysiology and regulatory influences that determine the internal distribution and external balance of K+ is critical in designing effective treatments to restore K+ homeostasis. We provide an up-to-date review of the regulatory aspects of normal K+ physiology as a preface to highlighting common disorders in K+ homeostasis and their treatment. This review of K+ homeostasis is designed as a resource for clinicians and a tool for educators who are teaching trainees to understand the pivotal factors involved in K+ balance.

Strategies to Counter Weight Loss-Induced Reductions in Metabolic Rate.

A significant percentage of the population is classified as obese, and there is a growing need to develop novel therapy to reduce body weight. It has long been appreciated that caloric restriction and exercise are the cornerstones of any weight loss method. This review outlines the challenges faced when attempting to achieve weight loss and the metabolic adaptations that ensue upon reductions in body weight which make sustaining weight loss extremely difficult. We discuss the need for novel approaches to weight loss that would increase basal metabolic rate and counter the biological adaptations that provide barriers for maintaining weight reduction. We introduce two metabolic processes, hypobaric hypoxia and cold exposure, which, when activated, cause increased metabolic rate even in the presence of reduced caloric intake. While we do not suggest that these are long-term viable options for methods to achieve weight loss, we are introducing these as pathways that may be targeted to eventually develop novel therapies to achieve sustainable weight loss.

Impact of estrogens and estrogen receptor-α in brain lipid metabolism.

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

Potassium Homeostasis in Health and Disease: A Scientific Workshop Cosponsored by the National Kidney Foundation and the American Society of Hypertension.

While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia. Fear of this often asymptomatic finding limits enthusiasm for recommending potassium intake and often limits the use of renin-angiotensin-aldosterone system blockers in patients with heart failure and chronic kidney diseases. New agents for managing hyperkalemia may alter the long-term management of heart failure and the hypertension, proteinuria, and further function loss in chronic kidney diseases. In this jointly sponsored effort between the American Society of Hypertension and the National Kidney Foundation, 3 panels of researchers and practitioners from various disciplines discussed and summarized current understanding of the role of potassium in health and disease, focusing on cardiovascular, nutritional, and kidney considerations associated with both hypo- and hyperkalemia.