In addition to reducing salt intake, consuming sufficient amounts of vegetables and fruits rich in potassium is an essential non-pharmacological approach for implementing hypertension management. Potassium not only lowers blood pressure but also prevents stroke and other cardiovascular diseases [1]. The Japanese Society of Hypertension recommends promoting potassium intake alongside salt reduction provided that kidney function is normal [2]. Multiple mechanisms are involved in the blood pressure-lowering and cardiovascular protective effects of potassium, one of which is natriuresis and the reduction in salt sensitivity. However, potassium loading promotes aldosterone secretion, a well-known stimulator of renal salt reabsorption. Experimental studies over the past decades have revealed that potassium loading suppresses renal salt reabsorption through mechanisms that do not require aldosterone, solving the above-mentioned apparent contradiction [3]. This mechanism is non-genomic and can in theory be observed within several hours; few studies tested whether this effect is also observed in humans.

By analyzing urinary extracellular vesicles (uEVs), we evaluated whether dietary potassium rapidly alters Na-Cl cotransporter (NCC) in the kidney, along with the increase in urinary Na levels. The study involved three healthy volunteers aged 26 to 57 years, with an eGFR range of 75 to 119 mL/min/1.73 m². All participants had no history of hypertension and provided informed consent (no. 2203). The participants consumed a high-potassium diet (approximately 2500 mg of potassium and 88 g of carbohydrates) and a low-potassium diet (approximately 80 mg of potassium and 70 g of carbohydrates) on separate days (Supplementary Table S1). Blood and urine samples were collected before the meal and 1, 2, and 3 hours post-meal. Electrolyte and creatinine levels were measured by the electrode method and enzymatic method, respectively (LABOSPECT 008α, Hitachi). Aldosterone levels were determined by CLEIA (Accuraseed, FUJIFILM). Insulin was measured by CLIA (Alinity i, Abbott). Isolation of uEVs was performed by the ultracentrifugation method as described previously [4] and is in accordance with the guidelines of the International Society for Extracellular Vesicles [5]. NCC levels were then determined by Western blotting and the signal was normalized to Alix abundance, a selective exosome marker.