This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar includes lively discussions based on cases, which are also partly included in this series as self-assessment questions. The first article in this series focuses on pathophysiology, symptoms, outcomes, and evaluation of hyponatremia, a common water and electrolyte disorder in clinical practice. Diagnosing the root cause(s) of hyponatremia can be challenging due to various etiologies and co-morbidities that affect water and electrolyte homeostasis, which can result in inappropriate management and worse outcomes in acute and chronic hyponatremia. This review provides an overview of pathophysiology, symptoms, outcomes, and evaluation of hyponatremia for better comprehension and improved clinical practice.

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.

This review article series on water and electrolyte disorders is based on the ‘Electrolyte Winter Seminar’ held annually for young nephrologists in Japan. The seminar features dynamic case-based discussions, some of which are included as self-assessment questions in this series. The second article in this series focuses on treatment of hyponatremia, a common water and electrolyte disorder frequently encountered in clinical practice. Hyponatremia presents diagnostic challenges due to its various etiologies and the presence of co-morbidities that affect water and electrolyte homeostasis. Furthermore, limited evidence, including a lack of robust randomized controlled trials, complicates treatment decisions and increases the risk of poor outcomes from inappropriate management of both acute and chronic hyponatremia. This review provides a comprehensive overview of treatment of hyponatremia for better comprehension and improved clinical practice.

This review article series on water and electrolyte disorders is based on the “Electrolyte Winter Seminar” that is held annually for young nephrologists in Japan. This seminar includes lively discussions based on cases, which have been partly included in this series as self-assessment questions. In this fourth article of the series, we have focused on the pathophysiology of potassium and the diagnosis of hyperkalemia. Hyperkalemia is associated with increased overall mortality, cardiovascular mortality, hospitalization, and progression to end-stage renal disease. Although most patients with hyperkalemia exhibit impaired kidney function, some exhibit normal kidney function. Therefore, accurately diagnosing the underlying cause of hyperkalemia is crucial for its appropriate management. In this review, we have first discussed the pathophysiology of potassium regulation. We have then highlighted the causes of hyperkalemia other than chronic kidney disease, including pseudohyperkalemia, which is often overlooked in clinical practice, and hypoaldosteronism, which can cause hyperkalemia even in patients with normal or mildly impaired kidney function. Finally, we have shared practical “Tips and Pearls” on hyperkalemia for clinicians that are applicable in daily practice.

Summary: The etiology of hyponatremia is assessed based on urine osmolality and sodium. We herein describe a 35-year-old Asian man with pulmonary tuberculosis and perforated duodenal ulcer who presented with hyponatremia with hourly fluctuating urine osmolality ranging from 100 to 600 mosmol/kg, which resembled urine osmolality observed in typical polydipsia and SIADH simultaneously. Further review revealed correlation of body temperature and urine osmolality. Since fever is a known non-osmotic stimulus of ADH secretion, we theorized that hyponatremia in this patient was due to transient ADH secretion due to fever. In our case, empiric exogenous glucocorticoid suppressed transient non-osmotic ADH secretion and urine osmolality showed highly variable concentrations. Transient ADH secretion-related hyponatremia may be underrecognized due to occasional empiric glucocorticoid administration in patients with critical illnesses. Repeatedly monitoring of urine chemistries and interpretation of urine chemistries with careful review of non-osmotic stimuli of ADH including fever is crucial in recognition of this etiology. Learning points: Hourly fluctuations in urine osmolality can be observed in patients with fever, which is a non-osmotic stimulant of ADH secretion. Repeated monitoring of urine chemistries aids in the diagnosis of the etiology underlying hyponatremia, including fever, in patients with transient ADH secretion. Glucocorticoid administration suppresses ADH secretion and improves hyponatremia even in the absence of adrenal insufficiency; the etiology of hyponatremia should be determined carefully in these patients.

This article is part of a review series on water and electrolyte disorders, based on the annual “Electrolyte Winter Seminar” for early-career nephrologists in Japan. The seminar features interactive case-based discussions, some of which are included as self-assessment questions. The fifth installment addresses the management of hyperkalemia. Hyperkalemia frequently occurs in patients with chronic kidney disease (CKD) and can become life-threatening when severe, necessitating prompt treatment regardless of its underlying cause. Renin–angiotensin system inhibitors (RASi) are a recognized risk factor for hyperkalemia in CKD; however, discontinuing RASi in response to elevated potassium levels may adversely affect patient outcomes. Although there are no formal criteria distinguishing acute from chronic hyperkalemia, symptoms presentation and potassium levels offer a practical guide for clinical management. This review covers standard treatment strategies for severe (symptomatic or acute) hyperkalemia in emergency and inpatient settings and discusses how to manage mild-to-moderate (asymptomatic or chronic) cases in CKD patients while continuing RASi therapy.