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

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
• preexisting diabetes
• post-transplant diabetes mellitus (PTDM)
• corticosteroids
• immunosuppressive regimen
• calcineurin inhibitors
• mTOR inhibitors
• belatacept

Article highlights

• Pre-existing kidney transplant recipients are at higher risk of acute T-cell mediated rejection as compared to pretransplant non-diabetic kidney recipients.

• Pre-existing diabetes increases the risk of sepsis after kidney transplantation and is an independent risk factor for infection-related mortality in kidney-allograft recipients.

• Diabetic kidney transplant recipients (pre-existing and PTDM) are at higher risk of cardiovascular (CV) complications as well as of CV-related death as compared to non-diabetic kidney recipients.

• ATG does not have a demonstrated effect on glycemic metabolism

• Data are not clear enough to assert that basiliximab is responsible for PTDM

• High doses of steroids are strongly associated with the risk of PTDM.

• MMF and AZA do not have a demonstrated effect on glycemic metabolism

• CNIs are strongly associated with PTDM. The risk is more important with TAC than with CSA.

• Low doses of steroids, minimization of tacrolimus exposure, and conversion from tacrolimus to mTOR-Is or to belatacept may be therapeutic options to prevent the risk of PTDM, although there may be a higher risk of rejection

• The role of mTORi in PTDM is controversial. Experimental data favor a higher risk of glycemic metabolism disorders. However, the clinical data are contradictory

• Belatacept is associated with better graft outcomes than CNIs. Its effect on diabetes seems neutral, although experimental data may suggest a protective role.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded