Diabetic kidney transplant recipients: Impaired infection control and increased alloreactivity

Abstract

Background: Post-transplantation diabetes mellitus (PTDM) has been associated with inferior patient and allograft outcomes. However, previous studies did not identify differences in infection control and alloreactivity.

Methods: We studied 449 kidney transplant recipients (KTRs) between 2005 and 2013. Fifty (11.1%) KTRs were diagnosed with PTDM and 60 (13.4%) KTRs with pre-existing diabetes. Samples were collected pretransplantation, at +1, +2, +3 months post-transplantation. CMV specific and alloreactive T cells were quantified by interferon-γ Elispot assay. Lymphocyte subpopulations were quantified by flow cytometry.

Results: Upon multivariate analysis, age, obesity, and the use of tacrolimus increased the risk of PTDM (P<.05). KTRs with pre-existing diabetes/PTDM showed higher rates of sepsis (P<.01). Total CD3+ and CD4+ T cell counts were significantly lower in KTRs with PTDM/pre-existing diabetes post-transplantation (P<.05). No differences were observed for CMV-specific T cells between any group (P>.05). KTRs developing PTDM showed increased frequencies of alloreactive T-cells post-transplantation (P<.05).

Conclusions: Our results suggest higher rates of infection in KTRs with pre-existing diabetes/PTDM that may be attributed to impaired overall immunity. Higher frequencies of alloreactive T cells contribute to inferior long-term outcomes. As acute rejection, but not pre-existing diabetes/PTDM, was associated with inferior allograft survival and function, maintaining adequate immunosuppression to prevent rejection seems important.

Keywords: T cells; alloreactivity; diabetes; post-transplantation diabetes mellitus; renal transplantation.