Hypokalemia: a practical approach to diagnosis and its genetic basis

Abstract

Hypokalemia is a common and important finding in hospitalized patients because it may provoke cardiac arrhythmias and/or respiratory arrest. Our aim is to suggest better diagnostic tools and therapeutic principles, and summarize new molecular advances that are linked to hypokalemia. Measurements in freshly-voided urine to evaluate potassium (K+) excretion and an assessment of the acid-base status in blood can help differentiate between the various causes of hypokalemia. In patients with a low rate of K+ excretion, hypokalemia can be explained by an acute shift of K+ into cells, intestinal K+ loss, or prior renal K+ excretion. Patients with a high rate of K+ excretion usually have metabolic acid-base disorders. In patients with hyperchloremic metabolic acidosis, an assessment of the rate of excretion of ammonium (NH4+) in the urine separates those with renal tubular acidosis (RTA) (low NH4+ excretion) from those with causes other than RTA. In patients with metabolic alkalosis, a high blood pressure helps to distinguish between a state with high mineralocorticoid activity from others with extracellular fluid (ECF) volume contraction. Measurement of renin activity, aldosterone, and cortisol levels in plasma help to differentiate between the causes with mineralocorticoid excess whereas the urine chloride (Cl-) concentration may reveal the basis for renal Na+ wasting and distinguish it from non-renal Na+ loss. The treatment of hypokalemia is guided by the risk imposed by hypokalemia, magnitude of the K+ deficit, route of the K+ administration, available K+ preparations, adjuncts to therapy, and special associated conditions. Recent molecular advances in inherited hypokalemic disorders affecting transcellular K+ shift, gastrointestinal and renal K+ excretion are also discussed.