The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in...

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K⁺) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K⁺ homeostasis, and we review the effects of dietary K⁺ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K⁺ secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.