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Published on: November 8, 2015
Post-transplant diabetes mellitus: the last 10 years with tacrolimus
1Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. lars.backman@surgery.gu.se
Insights
Post-transplant diabetes mellitus (PTDM) incidence has significantly decreased in renal transplant patients. Lower tacrolimus doses and corticosteroid elimination in immunosuppression protocols reduce PTDM risk without affecting graft efficacy.
Area of Science:
- Nephrology
- Immunosuppression
- Transplantation
Background:
- Post-transplant diabetes mellitus (PTDM) is a significant risk factor for cardiovascular disease and mortality in kidney transplant recipients.
- PTDM often develops within 3 months post-transplantation, with immunosuppressive regimens being a major determinant of its incidence.
- Corticosteroids and high-dose calcineurin inhibitors (cyclosporine, tacrolimus) are identified as key risk factors for PTDM.
Purpose of the Study:
- To analyze the impact of various tacrolimus-based immunosuppressive regimens and study initiation time on PTDM incidence over the past decade.
- To evaluate the role of evolving immunosuppressive strategies in mitigating PTDM development in renal transplantation.
Main Methods:
- Retrospective analysis of tacrolimus-based immunosuppressive protocols used in renal transplantation over a ten-year period.
- Investigation into the correlation between specific drug dosages, corticosteroid use, and the incidence of PTDM.
- Assessment of the time trend in PTDM incidence in relation to changes in immunosuppressive protocols.
Main Results:
- A notable decline in PTDM incidence was observed, decreasing from 20% in the early 1990s to 0-5% in recent studies.
- Lower tacrolimus blood levels and the elimination of corticosteroids were associated with significantly reduced PTDM rates.
- Immunosuppressive regimen composition and dosage were found to be critical factors influencing PTDM development.
Conclusions:
- Optimized tacrolimus-based immunosuppressive protocols, characterized by reduced drug exposure and corticosteroid withdrawal, have successfully lowered PTDM incidence in renal transplantation.
- These evolving strategies demonstrate the potential to decrease PTDM-related complications while maintaining graft survival and efficacy.
- Minimizing the overall immunosuppressive medication burden is crucial for preventing PTDM in transplant recipients.
Abstract:
Post-transplant diabetes mellitus (PTDM) is a key risk factor for cardiovascular disease, which itself is a leading cause of death with a functioning graft. In a published review of the literature on PTDM and immunosuppression, most cases of PTDM were diagnosed within the first 3 months post-transplantation. In renal transplantation, the type of immunosuppressive regimen accounted for 74% of the variability recorded in the 12 month cumulative incidence of PTDM between studies (P = 0.0004), with inclusion of corticosteroids and/or high-dose ciclosporin or tacrolimus being the main risk factors for development of PTDM. Other key risk factors were recipient age and non-white ethnicity. The diabetic potential of any immunosuppressive protocol depends on the combination of agents used and the corresponding doses. Therefore, we conducted an analysis to investigate the impact of different tacrolimus-based regimens employed over the past decade together with the time of study initiation on the incidence of PTDM. There was a progressive decline in the incidence of PTDM with year of study initiation, from 20% in the early 1990s to 0-5% most recently. The low incidences of PTDM were achieved with those protocols employing lower blood levels of tacrolimus and/or corticosteroid elimination. These results emphasize the importance of reducing the immunosuppressive medication load and the role of corticosteroids in the development of PTDM. Evolving tacrolimus-based immunosuppressive protocols for renal transplantation over the last 10 years, particularly in terms of tacrolimus dosing and corticosteroid elimination, has led to a reduction in PTDM-related morbidity without compromising efficacy.
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