Glycemic Stability Through Islet-After-Kidney Transplantation Using an Alemtuzumab-Based Induction Regimen and Long-Term Triple-Maintenance Immunosuppression

Am J Transplant. 2016 Jan;16(1):246-53. doi: 10.1111/ajt.13425. Epub 2015 Aug 19.

Abstract

Pancreatic islet transplantation is performed in a select group of patients with type 1 diabetes mellitus. Immunosuppressive regimens play an important role in long-term islet function. We aimed to investigate the efficacy of islet transplantation in patients with type 1 diabetes and a previous kidney transplantation using an alemtuzumab-based induction regimen and triple maintenance immunosuppression. Patients with type 1 diabetes, who had received a kidney transplant previously, were treated with alemtuzumab as induction therapy for their first islet transplantation and basiliximab induction therapy for subsequent islet transplantations. Maintenance immunosuppression consisted of triple immunosuppression (tacrolimus, mycophenolate mofetil, and prednisolone). Thirteen patients (age 50.9 ± 9.2 years, duration of diabetes 35 ± 9 years) received a total of 22 islet transplantations. One- and 2-year insulin independence was 62% and 42%, respectively; graft function was 100% and 92%, respectively. HbA1c dropped from 57.2 ± 13.1 (7.4 ± 1.2%) to 44.5 ± 11.8 mmol/molHb (6.2 ± 0.9%) (p = 0.003) after 2 years. Six of 13 patients suffered from severe hypoglycemia before islet transplantation. After transplantation, severe hypoglycemia was restricted to the only patient who lost graft function. Creatinine clearance was unchanged. Islet-after-kidney transplantation in patients with type 1 diabetes using an alemtuzumab-based induction regimen leads to considerable islet allograft function and improvement in glycemic control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / surgery*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Glucose Tolerance Test
  • Glycemic Index*
  • Graft Rejection / drug therapy*
  • Graft Rejection / epidemiology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Islets of Langerhans Transplantation*
  • Kidney Function Tests
  • Kidney Transplantation*
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Postoperative Complications
  • Prednisolone / therapeutic use
  • Prognosis
  • Risk Factors
  • Tacrolimus / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Blood Glucose
  • Immunosuppressive Agents
  • Alemtuzumab
  • Prednisolone
  • Mycophenolic Acid
  • Tacrolimus