Nephrology and Hypertension

Editorial introductions No abstract available

Editorial: Novel therapeutic options for management of electrolyte disorders No abstract available

Advances in management of chronic metabolic acidosis in chronic kidney disease Purpose of review Chronic metabolic acidosis is a common complication of chronic kidney disease (CKD) and is associated with adverse consequences, such as CKD progression and muscle wasting. We review the findings from recent clinical trials that have examined the effects of sodium bicarbonate therapy and veverimer in patients with CKD and chronic metabolic acidosis. Recent findings There are four recent clinical trials on chronic metabolic acidosis of CKD. In a pilot, cross-over study, 6 weeks of sodium bicarbonate therapy improved vascular endothelial function, measured by brachial artery flow-mediated dilation. In a single-center, randomized, open-label study, 6 months of sodium bicarbonate therapy increased muscle mass and lean body mass, and preserved kidney function. The other two clinical trials (phase 1/2 and phase 3 studies) examined the effects of veverimer, which is a hydrochloric acid binder. The phase 3 study showed that 12-weeks of veverimer increased serum bicarbonate levels and might improve physical function. The effects of veverimer on CKD progression, physical function and cardiovascular endpoints as well as its long-term safety are yet to be determined. Summary Recent studies suggest that sodium bicarbonate therapy may improve vascular endothelial function and muscle mass, and preserve renal function. Veverimer increases serum bicarbonate level and could be a potential new therapeutic option for treating chronic metabolic acidosis.

Updates on medical management of hyperkalemia Purpose of review Hyperkalemia is a potentially fatal electrolyte disorder, more commonly present when the potassium excretion capacity is imparied. Hyperkalemia can lead to adverse outcomes, especially due to severe cardiac arrhythmias. It can also impair the cardiovascular effects of renin–angiotensin–aldosterone system inhibitors (RAASis) and potassium rich diets, as hyperkalemia frequently leads to their discontinuation. Recent findings Potassium is a predictor of mortality and should be monitored closely for patients who are at risk for hyperkalemia. Acute hyperkalemia protocols have been revised and updated. Randomized trials have shown that the new anti-hyperkalemic agents (patiromer and zirconium cyclosilicate) are effective hyperkalemia treatment options. The use of anti-hyperkalemic agents may allow for a less restrictive potassium diet and lower RAASi discontinuation rates. Summary Hyperkalemia should be monitored closely for high-risk patients, as it is associated with adverse outcomes. New therapies have demonstrated effective control, offering hope for potential use in patients that would benefit from diet or medications associated with an increase in serum potassium, indicating that the use of hyperkalemic agents can be associated with better outcomes.

Recent developments in the management of acute and chronic hyponatremia Purpose of review The aim of the study is to review recent studies on the management of acute and chronic hyponatremia. Recent findings In acute symptomatic hyponatremia, bolus infusion of hypertonic saline improves hyponatremia and neurological status more quickly than continuous infusion. In chronic hyponatremia, newly identified predictors of nonresponse to fluid restriction include a high urine osmolality (>500 mOsm/kg) and high urine sodium (>133 mmol/l). Vasopressin-receptor antagonists effectively raise the serum sodium concentration in patients with euvolemic or hypervolemic hyponatremia but have a risk of overcorrection, even at low doses. Several observational studies now support the use of urea for a more gradual correction of hyponatremia without a risk of overcorrection. Recently identified risk factors for overcorrection include lower serum sodium at presentation, polydipsia, hypovolemia, and early urine output during treatment. Specific treatments with potential efficacy are the use of intravenous albumin for hyponatremia because of liver cirrhosis, and fludrocortisone for hyponatremia in tuberculous meningitis. Summary The recent data will help to further optimize and personalize the management of patients with acute and chronic hyponatremia. However, most data are still observational and retrospective. Therefore, the field is in need of prospective studies comparing interventions for chronic hyponatremia and focusing on patient-relevant outcomes.

Hyponatremia in patients with cancer Purpose of review Hyponatremia is seen commonly in patients with cancer and is associated with increased mortality and morbidity. Understanding the proper diagnosis and therapy of cancer-associated hyponatremia is critical to ensure improved outcomes. Recent findings The most common cancers associated with hyponatremia are the various forms of lung cancer with incidences approaching 25–45%. The most common causes of hyponatremia in cancer patients are the syndrome of inappropriate antidiuretic hormone secretion [syndrome of inappropriate antidiuretic hormone (ADH)] and volume depletion. Proper diagnosis rests on clinical information supplemented by laboratory studies and is critical to ensure appropriate therapy. In recent years, the development of drugs that specifically antagonize the vasopressin type 2 receptor in the distal tubule have offered targeted and highly effective therapies for syndrome of inappropriate ADH. Summary Hyponatremia in cancer patients generally indicates advanced or severe disease but proper therapy that targets the underlying process can improve outcomes.

Hyperphosphataemia in 2019: have we made progress? Purpose of review This review describes recent developments in the management of serum phosphate in dialysis patients, with a focus on the development of recent trials which randomize patients to different levels of control. Recent findings We review the uncertainties around clinical benefits of serum phosphate control and alternative approaches to current management, as well as a multinational attempt to conduct randomized controlled trials in this area. We discuss novel methods of limiting oral phosphate absorption. Summary Although numerous guidelines and target ranges for serum phosphate management exist, they are largely based on observational data and there is no definitive evidence that good control improves the length or quality of life of dialysis patients. New phosphate binders continue to appear on the market with increasing financial cost but without additional meaningful outcome data. Two recently published trials have demonstrated the feasibility of a large-scale study of differing phosphate levels to test the hypothesis that reduction of serum phosphate is beneficial to dialysis patients. Restriction of oral phosphate intake should not be overlooked.

Revisiting therapeutic options for calciphylaxis Purpose of review Calciphylaxis is a disorder of cutaneous microvascular calcification and thrombosis leading to chronic, excruciatingly painful, progressive wounds with a high risk of sepsis and death. The diagnosis and treatment of calciphylaxis presents significant challenges. A poorly understood disease, the management of calciphylaxis has mostly been restricted to wound management and a few novel therapies. Data from patient registries and new studies on causal pathways is stimulating the development of pathogenesis-based medical therapies. Recent findings Much needed clinical trials are now underway to examine the safety and efficacy of sodium thiosulfate and other therapeutics for the indication of calciphylaxis. There is emerging data suggesting a potential role of therapeutic anticoagulation in these patients. There has also been a renewed emphasis on patient-oriented outcomes, such as improvement of pain scores and quality-of-life indices. Summary This review highlights ongoing clinical trials studying therapeutic options in calciphylaxis and emphasizes the causal pathways that led to the development of such therapies.

The Drosophila Malpighian tubule as a model for mammalian tubule function Purpose of review Studies of the genetic model organism, Drosophila melanogaster, have unraveled molecular pathways relevant to human physiology and disease. The Malpighian tubule, the Drosophila renal epithelium, is described here, including tools available to study transport; conserved transporters, channels, and the signaling pathways regulating them; and fly models of kidney stone disease. Recent findings Tools to measure Malpighian tubule transport continue to advance, including use of a transgenic sensor to quantify intracellular pH and proton fluxes. A recent study generated an RNA-sequencing-based atlas of tissue-specific gene expression, with resulting insights into Malpighian tubule gene expression of transporters and channels. Advances have been made in understanding the molecular physiology of the With No Lysine kinase–Ste20-related proline/alanine rich kinase/oxidative stress response kinase cascade that regulates epithelial ion transport in flies and mammals. New studies in Drosophila kidney stone models have characterized zinc transporters and used Malpighian tubules to study the efficacy of a plant metabolite in decreasing stone burden. Summary Study of the Drosophila Malpighian tubule affords opportunities to better characterize the molecular physiology of epithelial transport mechanisms relevant to mammalian renal physiology.

Fibroblast growth factor 23 and phosphate homeostasis Purpose of review The current review highlights recent advances in the area of renal tubular phosphate transport and its regulation by fibroblast growth factor 23 (FGF23), a potent regulator of phosphate homeostasis. Recent findings Recent studies demonstrate that FGF23 binds to both membrane and soluble form of α-klotho to activate FGF receptor signaling pathways. Parathyroid hormone and FGF23 equivalently decrease sodium-dependent phosphate cotransport but the effect is not additive, suggesting a shared but not synergistic mechanism of action. Crosstalk occurs downstream of parathyroid hormone-receptor and FGF23-receptor signaling and converge at the level of the scaffolding protein, sodium-hydrogen exchanger regulatory factor-1. A novel mechanism for phosphate efflux through the basolateral membrane of renal proximal tubular epithelia via an atypical G-protein coupled receptor, Xenotropic and polytropic retrovirus receptor 1 (XPR1), was recently identified. Conditional deletion of Xpr1 gene in renal proximal tubules in mice leads to hypophosphatemic rickets and Fanconi syndrome establishing an important role for XPR1 in phosphate homeostasis. A novel anti-FGF23 antibody, burosumab, was recently approved to treat X-linked hypophosphatemia, a human disorder of FGF23 excess. Summary Significant advances in understanding the cellular and molecular aspects of renal tubular phosphate transport and its regulation by FGF23 has led to the discovery of novel therapeutics to treat human disorders of phosphate homeostasis.