Iatrogenic hypercalcemia in a patient with type 2 diabetes and chronic kidney disease

Abstract

Introduction: The introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and non-steroidal mineralocorticoid receptor antagonists (nsMRA) has significantly improved outcomes in patients with type 2 diabetes, obesity and chronic kidney disease (CKD). However, the increasing use of combination therapies may result in previously unrecognized adverse drug interactions. Case description: We report the case of a 59-year-old man with obesity, type 2 diabetes, CKD stage 3b, albuminuria and established cardiovascular disease receiving optimized treatment with renin–angiotensin–aldosterone system blockade, sodium-glucose cotransporter-2 inhibition, semaglutide and finerenone. Mild finerenone-associated hyperkalaemia was treated with calcium polystyrene sulfonate. Several weeks later, the patient developed symptomatic severe non-parathyroid hormone-mediated hypercalcemia accompanied by acute kidney injury, fatigue, muscle weakness, constipation, polyuria and polydipsia. Extensive investigations excluded solid and haematological malignancy, granulomatous disease and endocrine disorders. Hypercalcemia was attributed to increased calcium absorption from calcium polystyrene sulfonate, likely facilitated by prolonged gastrointestinal transit secondary to semaglutide-induced constipation. Treatment consisted of withdrawal of the offending medications, aggressive intravenous hydration, loop diuretics and a reduced dose of intravenous zoledronic acid, resulting in normalization of serum calcium and recovery to baseline kidney function. Semaglutide and finerenone were subsequently reintroduced without recurrence of hyperkalaemia or hypercalcemia, eliminating the need for potassium binders. Conclusion: This case highlights a previously unreported mechanism of iatrogenic hypercalcemia resulting from the interaction between contemporary cardio-renal-metabolic therapies and underscores the importance of careful monitoring for unexpected adverse effects when combining newer agents with established treatments.