Hyperkalemia: from pathophysiology to treatment Free

Kidneys play an important role in potassium balance whether kidney function is normal or glomerular filtration rate (GFR) is reduced. In addition to the role played by GFR, potassium is regulated by substantial proximal tubule reabsorption and extremely controlled secretory/absorptive processes taking place along the distal tubule and the collecting duct. Hyperkalemia ensues when renal potassium excretion is reduced by decreases in GFR, tubular flow, distal sodium delivery or the expression of selective ion transporters located along the aldosterone-sensitive distal nephron.

Hyperkalemia is a potentially life-threatening condition occurring not infrequently in patients with heart failure, renal disorders and the use of specific drugs like renin–angiotensin–aldosterone inhibitors that are beneficial for the treatment of these diseases. This may implicate that hyperkalemia, or rather the concern of incurring hyperkalemia, causes the reduction of the prescription of these important classes of drugs. In addition, epidemiologic data indicate strong associations of morbidity and mortality in patients with hyperkalemia, only partly as a consequence of the increase in cardiac arrhythmia episodes. On the basis of these considerations, it is clear that the clinical use of newer potassium-lowering agents is critical both for the reduction of the mortality linked to hyperkalemia and for the possibility of avoiding an underutilization of important, but potentially medications that may cause hyperkalemia.

In this supplement of Nephrology Dialysis Transplantation, we have tried, starting from a review of the pathophysiology of potassium metabolism and underlining the importance of this ion in the regulation of the main cellular processes, to report all the necessary evidence for the correct use of these new potassium-lowering agents.

A final point that we would like to highlight, and which deserves further studies by the scientific community, is the definition of hyperkalemia. Currently, for most of the scientific societies, hyperkalemia (mild) is defined as serum potassium level >5.0 mEq/L, moderate between 5.5 and 6.0 mEq/L, and severe >6.0 mEq/L. Although epidemiological studies show worse outcomes for subjects in whom serum potassium exceeds even the normal values, it is unclear if these associations imply any causality. In fact, clinical studies in patients with hyperkalemia suggest that the serum potassium value that warrants active treatment should be revised upwards. For this reason, there is a commission within the European Best Practice guidelines that is working to resolve this important aspect. The conclusions of this group of experts will eventually help to avoid indiscriminate and unjustified use of the new potassium binders.