Tacrolimus Induced Hyperosmolar Hyperglycemic State In A Kidney Transplant Recipient

Tacrolimus is a calcineurin inhibitor used for immunosuppression in organ transplant patients. In 74% of organ recipients, it can destroy pancreatic beta-islet cells and create peripheral insulin resistance, thereby causing new onset diabetes after transplant (NODAT). It has been reported to cause diabetic ketoacidosis (DKA), however, its association with hyperosmolar hyperglycemic state (HHS) is not well described. We present here a rare case of HHS as the initial presentation of NODAT due to Tacrolimus.

Case Description:

A 60-year-old African American man with End Stage Renal Disease secondary to chronic glomerular nephritis underwent a deceased donor left kidney transplant, managed with tacrolimus 0.5mg twice a day for six years. On a routine well check, his blood glucose was found to be greater than 600 mg/dL and he was sent to the emergency department. On presentation, he appeared drowsy but arousable. Vital signs were blood pressure 140/90 mmHg, heart rate 62 beats/min, respiratory rate 18 breaths/min, pulse oximetry 99% on room air and temperature 98.2 degrees. Physical examination was notable for dry mucus membranes. Laboratory studies revealed blood glucose 1053 mg/dL, serum osmolarity 327 mOsm/kg, and bicarbonate 19 mmol/L with normal serum ketones and normal anion gap. Hemoglobin A1c was 10.9%. Other laboratory investigations were within normal limits. CT scan of the head was unremarkable. A diagnosis of HHS and NODAT was made, and he was started on appropriate therapy per protocol including insulin infusion and aggressive hydration. Due to lack of other risk factors, his clinical presentation was attributed to tacrolimus. He was discharged on 45 units of insulin glargine at bedtime and 12 units of insulin lispro before meals. Tacrolimus dose remained unchanged as it was necessary for post-transplant maintenance. He was educated about his new diagnosis and advised outpatient follow-up.

Discussion:

Though several cases of tacrolimus-induced DKA have been reported, there are very few recorded cases of tacrolimus-induced HHS. Patients with NODAT are at risk for decreased allograft viability and survival, thus making its diagnosis and prompt treatment imperative. Our case highlights the need for lifelong monitoring of HbA1c and fasting blood glucose in post-transplant patients receiving tacrolimus. Given the high morbidity and mortality associated with NODAT and its complications, further investigation is warranted into prevention strategies and consideration of alternative or novel immunosuppressive regimens in those receiving tacrolimus. Additionally, patient education regarding dietary modification, exercise, and weight loss could help reduce the risk of NODAT development.