tacrolimus and Diabetic-Ketoacidosis

Immunosuppressive agents such as tacrolimus (TAC) and cyclosporin might cause glycemic disorders by suppressing insulin production. However, only a few cases of diabetic ketoacidosis (DKA) with longitudinal evaluation of endogenous insulin secretion related to TAC administration have been reported.. A 59-year-old Asian woman, who received prednisolone and TAC 4.0 mg for the treatment of anti-aminoacyl-tRNA synthetase antibody-positive interstitial pneumonia, was admitted to our hospital due to impaired consciousness and general malaise.. She had metabolic acidosis; her plasma glucose, fasting serum C-peptide immunoreactivity (CPR), and urinary CPR levels were 989 mg/dL (54.9 mmol/L), 0.62 ng/mL, and 13.4 μg/d, respectively. No islet-related autoantibodies were detected. Therefore, she was diagnosed with TAC-induced DKA.. Intravenous continuous insulin infusion and rapid saline infusion were administered. TAC was discontinued because of its diabetogenic potential.. Sixteen weeks after cessation of TAC administration, she showed good glycemic control without administration of insulin or any oral hypoglycemic agents; her serum CPR level also improved dramatically. These findings suggested that TAC-induced pancreatic beta cell toxicity is reversible.. We reported a case of TAC-induced DKA with subsequent recovery of pancreatic beta cell function after cessation of TAC, resulting in good glycemic control. As TAC is widely used, we should pay attention to patients' glucose levels even though the TAC concentrations used are within the target range. Furthermore, dose reduction or cessation of TAC should be considered if hyperglycemia is detected during administration of this agent.

Topics: Diabetic Ketoacidosis; Female; Humans; Immunosuppressive Agents; Insulin Secretion; Middle Aged; Tacrolimus

Transplant recipients are at high risk of coronavirus disease 2019, and a timely supply of antivirals should be prioritized for those patients. Complicated drug‒drug interactions limit the use of Paxlovid (nirmatrelvir/ritonavir) coadministered with tacrolimus. Here, we report a patient with a kidney transplant who received Paxlovid and reduced-dose tacrolimus at the same time and suffered a severe tacrolimus toxicity.. We present a 56-year-old man of Han ethnicity with a kidney transplant who suffered from coronavirus disease 2019 twice. For the first infection, the immunosuppressants were substituted by dexamethasone when the patient used Paxlovid, and everything went well. For the second time, tacrolimus at a reduced dose concomitant with Paxlovid caused severe diarrhea, inducing combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state.. This case challenges the dose-adjustment strategy of managing drug‒drug interactions. We suggest that tacrolimus should be stopped when Paxlovid is applied and that corticosteroids could be a good substitution.

Topics: COVID-19; Diabetes Mellitus; Diabetic Ketoacidosis; Diarrhea; Drug Interactions; Humans; Kidney Transplantation; Middle Aged; Tacrolimus

Calcineurin inhibitors (CNIs) are often associated with abnormalities in glucose and lipid metabolism. Tacrolimus is the most potent CNI which is nowadays used almost universally as a part of triple-drug immunosuppression after kidney transplantation. Tacrolimus can cause islet cell damage and decrease in insulin secretion which can lead to post-transplant diabetes mellitus and rarely diabetic ketoacidosis. Although rare, acute pancreatitis has also been implicated by a few case reports to be associated with tacrolimus. However, tacrolimus-induced acute pancreatitis has not been reported in pediatric kidney transplant recipient till date.. We report the first case of tacrolimus-induced acute pancreatitis in association with hypertriglyceridemia and DKA in a child early after kidney transplant. The patient was managed with supportive treatment, and tacrolimus was stopped for three days and then switched to cyclosporine-based regimen. The patient became euglycemic within 8 weeks of switching to cyclosporine and did not have any recurrence of pancreatitis.. Tacrolimus-induced pancreatitis is rare in the setting of kidney transplants and prompt diagnosis and management can lead to a successful outcome.

Topics: Adolescent; Combined Modality Therapy; Diabetic Ketoacidosis; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Pancreatitis; Tacrolimus; Tomography, X-Ray Computed

New-onset diabetes mellitus after solid-organ transplant makes for complicated tacrolimus immunosuppression. However, tacrolimus-associated diabetic ketoacidosis has not been reported in bone marrow transplant. We report 24-year-old women, hospitalized with diabetic ketoacidosis, 70 days after undergoing a bone marrow transplant with tacrolimus immunosuppression. Clinicians should be wary about tacrolimus levels and the risk of hyperglycemic states after bone marrow transplant as with other solid-organ transplants.

Topics: Bone Marrow Transplantation; Calcineurin Inhibitors; Cyclosporine; Diabetic Ketoacidosis; Drug Monitoring; Drug Substitution; Female; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Tacrolimus; Transplantation, Homologous; Treatment Outcome; Young Adult

New-onset diabetes after transplantation (NODAT) is a common metabolic complication. Most conventional immunosuppressive medications, especially steroids and tacrolimus, are responsible for its development. NODAT may rarely be associated with severe, life-threating complications in kidney transplantation recipients.. A 44-year-old man was admitted to our polyclinic for a routine post kidney transplantation visit. He reported polyuria, polydipsia, and general weakness. The patient had undergone preemptive, living-related kidney transplantation 5 weeks previously. Immunosuppressive treatment comprised tacrolimus, prednisolone, and mycophenolate mofetil. Physical examination revealed no abnormalities except signs of mild dehydration. Although he had no history of diabetes before kidney transplantation and his serum fasting glucose levels were within the reference range at the follow-up visits, his laboratory tests revealed high serum glucose and creatinine levels, ketosis, and metabolic acidosis. Our diagnosis was NODAT with diabetic ketoacidosis and prerenal azotemia. Initial treatment comprised intravenous saline and insulin infusion and subsequently involved intensive subcutaneous insulin administration. Despite the intensive insulin therapy and reduction of the tacrolimus dose, sufficient glucose regulation was not achieved. Tacrolimus was switched to everolimus on day 6 of hospitalization. The patient's insulin requirement gradually decreased to one-half of the primary dose over the following several days, and he was discharged on day 10 with successful serum glucose regulation. Although the diabetogenic potential of sirolimus is similar to that of tacrolimus, the impact of everolimus on glucose metabolism remains unclear.. We have reported a life-threating metabolic complication associated with tacrolimus and successful treatment of NODAT by switching from tacrolimus to everolimus.

Topics: Adult; Diabetic Ketoacidosis; Everolimus; Humans; Immunosuppressive Agents; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Male; Risk Factors; Tacrolimus

Tacrolimus, a reversible calcineurin inhibitor, is known for its diabetogenic potential. The incidence of diabetes is less frequent among the patients of nephrotic syndrome in comparison to organ transplant recipients. Diabetic ketoacidosis (DKA) is even rarer. DKA as the first presentation of new onset tacrolimus induced transient type 1 diabetes despite a lower dose range and low trough level of the drug is being reported in a 12-y-old girl with steroid resistant nephrotic syndrome.

Topics: Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Immunosuppressive Agents; Nephrotic Syndrome; Tacrolimus

New-onset diabetes mellitus after transplant is a well-recognized complication of tacrolimus immunosuppression and commonly occurs as a form of type 2 diabetes mellitus. However, tacrolimus-associated acute pancreatitis causing diabetic ketoacidosis has not been reported in heart transplant patients. We report a 22-year-old women hospitalized owing to diabetic ketoacidosis associated with acute pancreatitis 7 months after a heart transplant. Her immunosuppression included tacrolimus. She was admitted with complaints of polydipsia, anorexia, and abdominal pain of 3 days' duration. Her initial laboratory test revealed a toxic level of tacrolimus (> 30 ng/mL), severe hyperglycemia (39 mmol/L), severe metabolic acidosis (pH 6.9), and ketonuria, although diabetes mellitus had never been diagnosed. Serum amylase and lipase levels and abdominal computed tomography suggested the presence of acute pancreatitis. After correcting the diabetic ketoacidosis and getting the tacrolimus level to the normal range, she was discharged home. Three months later, insulin was replaced with oral hypoglycemic agents. Pancreatitis can present with diabetic ketoacidosis in the recipient of a heart transplant treated with tacrolimus. Clinicians should pay more attention to tacrolimus levels and the risk of pancreatitis.

Topics: Acute Disease; Cardiomyopathy, Dilated; Diabetic Ketoacidosis; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Insulin; Pancreatitis; Risk Factors; Sodium Bicarbonate; Tacrolimus; Treatment Outcome; Young Adult

Diabetic ketoacidosis in patients receiving tacrolimus in the post-transplant setting is rare. We describe two such cases in solid-organ transplant recipients. The first patient, a 17-year-old male, presented with severe diabetic ketoacidosis and was managed with intravenous fluids and insulin infusion. He was a known case of Laurence-Moon-Bardet-Biedl syndrome and had received a renal transplant 2 years ago and was receiving tacrolimus since then. Although diabetic ketoacidosis resolved in 24 hours, large doses of subcutaneous insulin (upto 130 units per day) were needed to keep serum glucose within the normal range. Substitution of tacrolimus with cyclosporine obviated the need for insulin or oral hypoglycaemics. The second patient, a 55-year-old woman, presented with a history of polyuria for 3 days. She had received a hepatic transplant 2 years ago and tacrolimus was being used since then. Mild diabetic ketoacidosis was managed with fluid resuscitation and subcutaneous insulin. Her insulin requirement after an uneventful recovery has been 54 - 70 units per day. Clinicians should be cognizant of the possibility of hyperglycaemic crisis presenting as sudden onset of diabetic ketocidosis in patients receiving tacrolimus. Use of an alternative calcineurin inhibitor may provide a safer solution to minimize future morbidity in such patients.

Topics: Adolescent; Diabetic Ketoacidosis; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Immunosuppressive Agents; Injections, Subcutaneous; Insulin; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Tacrolimus; Treatment Outcome

The development of NODM is a common metabolic complication after liver transplantation. Presentation of post-liver transplant diabetes mellitus with DKA is rare especially among pediatric patients. We reported three pediatric patients who presented with DKA after liver transplantation. The underlying diseases leading to transplantation were cryptogenic liver cirrhosis, Wilson disease, and congenital hepatic fibrosis. None of the three patients had a history of diabetes prior to transplantation and all of them were cases of NODM after transplantation. All three patients presented with severe hyperglycemia, significant ketosis, and metabolic acidosis of variable severity. All of them received tacrolimus as one of the immunosuppressant agents. The patients received a liver transplant from a DD. The patients were treated with intravenous insulin injection (0.1 U/kg/h) and recovered from DKA, but one case expired in the intensive care unit because of bacterial sepsis after recovery from DKA. Our experience suggests that PTDM may result in ketoacidosis, and we emphasize the importance of paying more attention to glucose metabolism and risk of diabetes mellitus in patients with immunosuppressive therapy, especially tacrolimus.

Topics: Adolescent; Child; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Humans; Immunosuppressive Agents; Insulin; Ketosis; Liver Transplantation; Male; Postoperative Complications; Tacrolimus

Although drugs used in renal transplant recipients such as steroids, cyclosporine, and particularly, tacrolimus have diabetogenic potential, diabetic ketoacidosis is uncommon. There are few data concerning the long-term follow-up of these patients. Diabetic ketoacidosis occurred in a renal transplant recipient following de novo development associated with tacrolimus.

Topics: Adult; Diabetic Ketoacidosis; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Peritoneal Dialysis, Continuous Ambulatory; Postoperative Complications; Tacrolimus; Treatment Outcome

Topics: Adult; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Insulin; Kidney Transplantation; Tacrolimus

The use of immunosuppressive agents is becoming more widespread, especially in the context of organ transplantation. We report a child with a complication, new-onset diabetes mellitus with diabetic ketoacidosis, associated with the use of one such agent, FK506 (tacrolimus).

Topics: Adolescent; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Tacrolimus

We report a 43-year-old man who presented diabetic ketoacidosis 1 year after receiving kidney transplantation. He was a recipient of renal transplantation treated with metyl-prednisolone and tacrolimus regimen. The serum level of tacrolimus was 12.4 ng/ml, and he showed hyperphagia before a month of admission. A week before admission, he was aware of polydipsia, polyuria, and general fatigue. He visited our hospital and was found to have severe hyperglycemia (925 mg/dl), significant ketosis and mild metabolic acidosis (pH 7.341), although he had not been diagnosed as diabetes mellitus. He administrated in our hospital, and was treated with insulin for 5 weeks. He was not obese (BMI = 18.2 kg/m(2)) and had no family history of type 2 diabetes. He was finally treated with diet therapy alone. The 24 h urine C-peptide secretion on the third hospital day was low (8.4 microg per day). However, no autoantibodies against pancreatic islets were positive, and his insulin secretion was recovered at discharge suggesting that he was not type 1 diabetes. Although, tacrolimus has been reported to cause or worsen diabetes mellitus, the present case suggests that it could cause severe decrease in insulin secretion which leading to diabetic ketoacidosis in lean subject without previous history of diabetes mellitus.

Topics: Adult; Diabetic Ketoacidosis; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Methylprednisolone; Tacrolimus; Treatment Outcome

Post-transplant diabetes mellitus, a complication due to corticosteroids and the calcineurin inhibitors, cyclosporine and tacrolimus (FK506), is commonly regarded as a form of type-2 (adult-onset) diabetes mellitus. Diabetic ketoacidosis, which requires relative insulin deficiency to impair fatty acid metabolism, is a complication of type-1 diabetes mellitus. We report three patients who presented with diabetic ketoacidosis post-transplant. All three patients presented with severe hyperglycemia, significant ketosis and metabolic acidosis of variable severity. One patient was a renal transplant recipient on a cyclosporine-based regimen. The other two patients were liver transplant recipients receiving either cyclosporine or tacrolimus-based immunosuppression. Both of the liver transplant recipients were found to have moderate to high serum levels of calcineurin inhibitors on presentation. The liver recipient on cyclosporine (Neoral) had a 4 hour post-dose level of 388 ng/ml and the patient on tacrolimus was found to have a trough level of 21.2 ng/ml. Our experience suggests that post-transplant diabetes mellitus, in association with calcineurin inhibition, may result in ketoacidosis either secondary to relative beta cell dysfunction, peripheral insulin resistance, or a combination of the two effects. Post-transplant diabetes mellitus can be an atypical form of adult-onset diabetes with features of both type I and type II diabetes mellitus.

Topics: Adult; Calcineurin; Cyclosporine; Diabetic Ketoacidosis; Female; Humans; Hyperglycemia; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Tacrolimus