Sudden cardiac arrest is the most common cause of death among patients with end-stage kidney disease (ESKD) maintained on hemodialysis. Here we sought to identify dialysis-related factors associated with this increased risk in a case-control study encompassing 43,200 patients dialyzed in outpatient clinics of a large organization. Within this group, we compared the clinical and dialysis-specific data of 502 patients who experienced a sudden cardiac arrest with 1632 age- and dialysis-vintage-matched controls. There were 4.5 sudden cardiac arrest events per 100,000 dialysis treatments during the 3-year study period. These patients were significantly more likely to have been exposed to low potassium dialysate of less than 2 meq/l. These differences could not be explained by predialysis serum potassium levels. There was no evidence for a beneficial effect of low potassium dialysate even among those with higher predialysis serum potassium levels. Other factors strongly associated with sudden cardiac arrest by multivariable analysis included increased ultrafiltration volumes, exposure to low calcium dialysate, and predialysis serum creatinine levels. These relationships persisted after adjustment for covariates, but traditional risk factors such as history of coronary heart disease and congestive heart failure were not significantly influential. Hence, our study suggests that modifications of the hemodialysis prescription may improve the risk of sudden cardiac arrest in patients with ESKD.

Overall body fluid concentration is regulated within a narrow range by the concerted action of the hypothalamic-pituitary axis to influence water intake through thirst and water excretion via the effect of vasopressin, or antidiuretic hormone, on renal collecting duct water permeability. Sodium is the principal extracellular cation; abnormalities in overall effective body fluid concentration, or tonicity, manifest as disturbances in serum sodium concentration. Depending on its severity and chronicity, hyponatremia can lead to significant symptoms, primarily related to central nervous system function. Failure to correct hyponatremia can lead to permanent neurologic damage, as can over rapid correction. It is thus essential to stay within specific limits for correction, particularly for chronic hyponatremia. Hypernatremia also leads to central nervous system dysfunction, although goals for its correction rate are less well established. This Core Curriculum article discusses the normal regulation of tonicity and serum sodium concentration and the diagnosis and management of hypo-and hypernatremia.

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Defective trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) is the most common cause of cystic fibrosis. In chloride-secreting epithelia, it is well established that CFTR localizes to intracellular organelles and to apical membranes. However, it is controversial whether secretagogues regulate the trafficking of CFTR. To investigate whether acute hormonal stimulation of chloride secretion is coupled to the trafficking of CFTR, we used the intact shark rectal gland, a model tissue in which salt secretion is dynamically regulated and both chloride secretion and cellular CFTR immunofluorescence can be quantified in parallel. In rectal glands perfused under basal conditions without secretagogues, Cl- secretion was 151+/-65 microeq/h/g. Vasoactive intestinal peptide (VIP), forskolin, and genistein led to 10-, 6-, and 4-fold increases in Cl- secretion. In basal glands, quantitative confocal microscopy revealed CFTR immunofluorescence extending from the apical membrane deeply into the cell (7.28+/-0.35 micron). During stimulation with secretagogues, apical extension of CFTR immunofluorescence into the cell was reduced significantly to 3.24+/-0.08 micron by VIP, 4.08+/-0.13 by forskolin, and 3.19+/-0.1 by genistein (P < 0.001). Moreover, the peak intensity of CFTR fluorescence shifted towards the apical membrane (peak fluorescence 2.5+/-0.13 micron basal vs. 1.51+/-0.06, 1.77+/-0.1, and 1.38+/-0.05 for VIP, forskolin, and genistein; all P < 0.001). The increase in both Cl- secretion and apical CFTR trafficking reversed to basal values after removal of VIP. These data provide the first quantitative morphological evidence for acute hormonal regulation of CFTR trafficking in an intact epithelial tissue.