Water and electrolyte abnormalities in novel pharmacological agents for kidney disease and cancer

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. This is the third article in this series that focuses on water and electrolyte disturbances caused by novel pharmacological agents for kidney disease and cancer. The advent of novel pharmacological agents in cardiorenal medicine and oncology has introduced both therapeutic benefits and challenges in managing medication-induced water and electrolyte disturbances. These medications, including sodium–glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (ns-MRAs), and immune checkpoint inhibitors (ICIs), significantly impact water and electrolyte homeostasis. SGLT2 inhibitors used widely in diabetes mellitus, heart failure, and chronic kidney disease mitigate hyperkalemia and hypomagnesemia but increase the risk of hypernatremia in patients on fluid restriction. Conversely, they are beneficial for managing hyponatremia in the syndrome of inappropriate antidiuresis (SIAD). ns-MRAs, prescribed for diabetic kidney disease, exhibit a high risk of hyperkalemia, particularly when combined with renin–angiotensin system inhibitors. ICIs, a breakthrough in oncology, frequently induce hyponatremia through immune-related adverse events, such as hypophysitis and non-immune-related adverse events like SIAD. Understanding the pathophysiology of these disturbances and implementing timely interventions, including hormone replacement and water and electrolyte management, is critical for optimizing treatment outcomes.