Renal potassium wasting from hydroxychloroquine at therapeutic doses: a case report

Hydroxychloroquine is a common disease-modifying treatment for systemic autoimmune disease and is usually well-tolerated. In acute hydroxychloroquine or chloroquine toxicity, hypokalemia typically reflects a transient intracellular potassium shift rather than true renal potassium losses. Persistent hypokalemia due to renal potassium wasting during therapeutic hydroxychloroquine use has not been well described. A 38-year-old woman with undifferentiated connective tissue disease developed recurrent symptomatic hypokalemia while receiving therapeutic hydroxychloroquine. She had normal renal function and blood pressure, and was not using diuretics or laxatives. Urine studies demonstrated inappropriate renal potassium loss during hypokalemia. Holding hydroxychloroquine for two weeks resulted in normalization of serum potassium levels, accompanied by symptom resolution. Rechallenge at a dose of 300 mg daily reproduced hypokalemia, which again resolved after drug discontinuation. The temporal relationship, objective urine indices, normalization after withdrawal, and recurrence with rechallenge suggest hydroxychloroquine-associated renal potassium wasting. The underlying mechanism remains uncertain and is hypothesized to involve tubular effects during chronic exposure. Clinicians should confirm the mechanism with urine studies when hypokalemia persists on hydroxychloroquine, consider a supervised medication hold when feasible, and pair potassium repletion with a potassium-sparing agent if the drug must continue.