A multidisciplinary group of researchers and clinicians met in October 2018 to identify evidence and address controversies in potassium management. Here we provide our overview of potassium homeostasis in health and disease and guidance for evaluation and management of dyskalemias in the context of kidney diseases, and indicate research priorities.

Purpose To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients. Methods We searched MEDLINE and EMBASE for relevant papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: “hyperkalemia,” “intensive care,” “acute kidney injury,” “acute kidney failure,” “hyperkalemia treatment,” “renal replacement therapy,” “dialysis,” “sodium bicarbonate,” “emergency,” “acute.” Reports from within the past 10 years were selected preferentially, together with highly relevant older publications. Results Hyperkalemia is a potentially life-threatening electrolyte abnormality and may cause cardiac electrophysiological disturbances in the acutely ill patient. Frequently used therapies for hyperkalemia may, however, also be associated with morbidity. Therapeutics may include the simultaneous administration of insulin and glucose (associated with frequent dysglycemic complications), β-2 agonists (associated with potential cardiac ischemia and arrhythmias), hypertonic sodium bicarbonate infusion in the acidotic patient (representing a large hypertonic sodium load) and renal replacement therapy (effective but invasive). Potassium-lowering drugs can cause rapid decrease in serum potassium level leading to cardiac hyperexcitability and rhythm disorders. Conclusions Treatment of hyperkalemia should not only focus on the ability of specific therapies to lower serum potassium level but also on their potential side effects. Tailoring treatment to the patient condition and situation may limit the risks. Electronic supplementary material The online version of this article (10.1186/s13613-019-0509-8) contains supplementary material, which is available to authorized users.

Background: Contemporary emergency department (ED) standard-of-care treatment of hyperkalemia is poorly described. Objective: Our aim was to determine the treatment patterns of hyperkalemia management in the ED.

Thymidylate synthase (TS) is indispensable in the de novo synthesis of dTMP. As such, it has been an important target at which anti-neoplastic drugs are directed. The fluoropyrimidines 5-fluorouracil and 5-fluoro-2-deoxyuridine are cytotoxic as a consequence of inhibition of TS by the metabolite 5-fluoro-2-deoxyuridine 5-monophosphate (FdUMP). This inhibition occurs through formation of a stable ternary complex among the enzyme, the nucleotide analog, and the co-substrate N 5 ,N 10 -methylenetetrahydrofolate. Numerous studies have shown that cellular concentrations of TS undergo about a 2-4-fold induction following treatment with TS inhibitors. An extensive body of in vitro studies has led to the proposal that this induction occurs because of relief of the translational repression brought on by the binding of TS to its own mRNA. In the current study, we have tested several predictions of this autoregulatory translation model. In contrast to expectations, we find that fluoropyrimidines do not cause a change in the extent of ribosome binding to TS mRNA. Furthermore, mutations within the mRNA that abolish its ability to bind TS have no effect on the induction. Finally, enzyme turnover measurements show that the induction is associated with an increase in the stability of the TS polypeptide. Our results, in total, indicate that enzyme stabilization, rather than translational derepression, is the primary mechanism of TS induction by fluoropyrimidines and call into question the general applicability of the autoregulatory translation model.Thymidylate synthase (TS, 1 EC 2.1.1.45) catalyzes the reductive methylation of dUMP by CH 2 H 4 PteGlu, generating dTMP and dihydrofolate (for a review, see Ref. 1). Because the enzyme is indispensable in the de novo synthesis of dTMP, it plays an important role in DNA replication in actively dividing cells and has been an attractive target at which anti-neoplastic agents are directed. Fluoropyrimidines (e.g. 5-fluorouracil and FdUrd) and, more recently, anti-folates (e.g. AG337, ZD1694, BW1843U89) have been useful in the clinical management of tumors of the breast, colon, stomach, and head and neck (2-5). Fluoropyrimidines exert their effects through formation of the nucleotide analog FdUMP, which inhibits TS via formation of a covalent complex containing the analog CH 2 H 4 PteGlu and the enzyme (1). This complex, which is termed the inhibitory ternary complex, is quite stable and leads to prolonged inhibition of the enzyme, depletion of dTMP pools, and thymineless death.A number of studies with cultured cell lines, tumor models, and clinical specimens have shown that TS inhibitors induce enzyme levels by about 2-4-fold (6 -8). Because response to TS-directed chemotherapy is dependent upon the enzyme concentration, such induction has been viewed as a potential barrier to successful therapeutic outcomes. As a result, there has been a great deal of interest in the mechanism of the induction and in strategies to ameliorate its effects. The increases in TS levels do not involve change...