POS-692 Euglycemic Diabetic Ketoacidosis Related to SGLT2 Inhibitor Use in Kidney Transplant Patient with Squamous Cell Carcinoma

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have renal protective effect in diabetic and non-diabetic patients with significant reduction of cardiovascular events. The data is emerging for the short-term efficacy and safety of SGLT2 inhibitor in diabetic kidney transplant patients. Diabetic ketoacidosis is a well recognized side effect of SGLT2i with variable predisposing factors. There is limited data regarding the use of SGLT2i in oncology patients. We described a case of diabetic kidney transplant patient on dapagliflozin who developed DKA during active therapy for squamous cell carcinoma. A 65 years old female, known to have hypertension and diabetes mellitus type 2 leading to end stage renal disease. She underwent living unrelated kidney transplantation in 2018. Her home medications included insulin glargine, dapagliflozin 10 mg, pantoprazole 40mg, prednisolone 7.5 mg daily, cyclosporine 125 mg q12 hours and atorvastatin 20mg. She was diagnosed with right inner cheek moderately differentiated keratinizing squamous cell carcinoma with submandibular lymphadenopathy (Stage: cT4aN2M0). She was initiated on concurrent chemotherapy (Cetuximab) and radiotherapy. Cycle 4 of therapy was complicated with poor oral intake and severe mucositis for 3 days prior to admission. She had evidence of acute kidney injury stage 1 in transplanted kidney (serum creatinine increased from baseline of 58 to 110 micromole/l). Other laboratory investigations revealed hyperkalemia 5.7mmol/l, metabolic acidosis 6mmol/l, high anion gap metabolic acidosis, normal lactate level, arterial PH of 7.1, ketones were positive in urine and blood glucose level of 12mmol/l. She was diagnosed with severe euglycemic diabetic ketoacidosis DKA, due to SGLT2i (dapagliflozin 10 mg) and starvation. She required critical care admission with rigorous IV hydration, insulin infusion per DKA protocol, IV sodium bicarbonate, IV hydrocortisone and IV cyclosporine. Her clinical condition improved by fifth day of critical care. Urinary tract infection and re-feeding syndrome post nasogastric enteral feeding complicated her hospital course. Dapagliflozin was held and next cycle of chemo-radiotherapy was delayed. Some of the potential risk factors for euglycemic DKA induced by SGLT2 inhibitors are infections, withdrawal of insulin, starvation, dehydration and acute kidney injury. The underlying pathophysiologic process of ketoacidosis induced by SGLT2 inhibitors is not well established. There are few case reports describing this complication in diabetic oncology patients, leading to discontinuation of the drug. The use of SGLT2 inhibitor is limited in diabetic kidney transplant patients and about 100 cases reported in literature without evidence of DKA in short-term follow up. To the best of our knowledge, this is the first case describing a successful management of dapagliflozin-induced euglycemic DKA in kidney transplant patient with squamous cell carcinoma. SGLT2 inhibitor associated eDKA is very rare in oncology patients and this is the first case reported in kidney transplant patient who was on active chemotherapy and radiotherapy for squamous cell carcinoma. We suggest to hold SGLT2i therapy during active oncology treatment especially in the setting on severe mucositis.