pre-existing diabetes and PTDM in kidney transplant recipients: how to handle immunosuppression

Expert Rev Clin Pharmacol. 2021 Jan;14(1):55-66. doi: 10.1080/17512433.2021.1851596. Epub 2020 Dec 15.

Abstract

Introduction: Preexisting diabetes (PD) and post-transplant diabetes mellitus (PTDM) are common and severe comorbidities posttransplantation. The immunosuppressive regimens are modifiable risk factors.

Areas covered: We reviewed Pubmed and Cochrane database and we summarize the mechanisms and impacts of available immunosuppressive treatments on the risk of PD and PTDM. We also assess the possible management of these drugs to improve glycemic parameters while considering risks inherent in transplantation.

Expert opinion: PD i) increases the risk of sepsis, ii) is an independent risk factor for infection-related mortality, and iii) increases acute rejection risk. Regarding PTDM development i) immunosuppressive strategies without corticosteroids significantly reduce the risk but the price may be a higher incidence of rejection; ii) minimization or rapid withdrawal of steroids are two valuable approaches; iii) the diabetogenic role of calcineurin inhibitors(CNIs) is also well-described and is more important for tacrolimus than for cyclosporine. Reducing tacrolimus-exposure may improve glycemic parameters but also has a higher risk of rejection. PTDM risk is higher in patients that receive sirolimus compared to mycophenolate mofetil. Finally, conversion from CNIs to belatacept may offer the best benefits to PTDM-recipients in terms of glycemic parameters, graft and patient-outcomes.

Keywords: Kidney transplantation; belatacept; calcineurin inhibitors; corticosteroids; immunosuppressive regimen; mTOR inhibitors; post-transplant diabetes mellitus (PTDM); preexisting diabetes.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Animals
  • Diabetes Mellitus / etiology
  • Diabetes Mellitus / physiopathology*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / methods
  • Risk Factors
  • Sepsis / etiology

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents