Severe hypercalcemia and hypernatremia in a patient treated with canagliflozin

[摘要] Drugs that inhibit the sodium-glucose co-transporter-2 (SGLT2) are an exciting novel, insulin-independent treatment fordiabetes that block glucose reabsorption from the proximal tubules of the kidney, leading to increased glucose excretion andlower blood glucose levels. Inhibition of SGLT2 activity also reduces sodium reabsorption, which together with glycosuriaproduces a mild diuretic effect with the potential for dehydration and hyperkalemia. We report on a 60-year-old man withuncontrolled type 2 diabetes treated with insulin, glimepiride, metformin and canagliflozin, who was admitted with alteredmental status after a syncopal episode. He had a 1-week history of ingestion of Tums for heartburn followed by poorappetite and lethargy. Laboratory work-up showed acute kidney injury, diabetic ketoacidosis (DKA), and parathyroidhormone-independent severe hypercalcemia of 17.4 mg/dl. DKA resolved with insulin treatment, and saline hydration ledto improvement in hypercalcemia and renal function over 48 h, but was accompanied by a rapid increase in the serumsodium concentration from 129 to 162 mmol/l despite changing fluids to 0.45% saline. Urine studies were consistent withosmotic diuresis. Hypernatremia was slowly corrected with hypotonic fluids, with improvement in his mental status over thenext 2 days. This is the first report of hypercalcemia associated with the use of a SLGT2 inhibitor. Although the exactmechanism is unknown, canagliflozin may predispose to hypercalcemia in patients ingesting excessive calcium because ofdehydration from osmotic diuresis, with reduced calcium excretion and possible increased intestinal calcium absorption.Saline therapy and osmotic diuresis may lead to hypernatremia from electrolyte-free water loss.

[学科分类] 血液学

[关键词] Adult;Male;White;United States;Parathyroid;Diabetes;Insulin;Iatrogenic disorder;Hypothyroidism;Hypertension;Diabetes mellitus type 2;Diabetic ketoacidosis;Hypercalcaemia;Hypernatraemia;Syncope;Delirium;Appetite reduction/loss;Fatigue;Diabetic ketoacidosis;Hypercalcaemia;Hypernatraemia;Sodium;Calcium (serum);Urea and electrolytes;Creatinine (serum);Phosphate (serum);Glucose (blood);Glucose (urine);Bicarbonate;PTH;25-hydroxyvitamin D3;Calcitriol;Beta-hydroxybutyrate;Sodium;Osmolality;Insulin;Calcitonin;Pamidronate;Bisphosphonates;Saline;Canagliflozin;Unusual effects of medical treatment;July;2015