New onset diabetes after transplant (NODAT) has been associated with an increased risk of infection and sepsis. Previous studies, however, failed to identify differences in overall immunity and infection control.

Here, we studied all adult kidney transplant recipients (KTRs) at our single transplant center transplanted between 2005 and 2012. 80 (10.3%) of 775 KTRs were diagnosed with NODAT and 114 (14.7%) of 775 KTRs were diagnosed with pre-existing diabetes. An age- and gender-matched control group of 208 KTRs without any type of diabetes was used for comparison. Samples were collected before transplantation and at +1, +2, +3, +6, and +12 months posttransplantation. CMV-specific and alloreactive T-cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations and cytokine levels.

Upon multivariate analysis age, body mass index, time on dialysis, and CMV reactivation increased the risk of NODAT after renal transplantation (p<0.05). Highest rates of acute rejection episodes were observed in KTRs developing insulin-dependent NODAT and KTRs with poorly controlled pre-existing diabetes (p<0.05). KTRs with poorly controlled diabetes showed significantly decreased allograft survival and lower eGFR (p<0.05). KTRs with pre-existing diabetes or NODAT showed significantly higher rates of septic complications compared to the control group (p<0.01). Total CD3+ and CD4+ T-cell counts were significantly lower in KTRs with pre-existing diabetes and NODAT during the early posttransplant period (p<0.05). KTRs developing NODAT showed a significant decrease in CMV-pp65- and CMV-IE1-specific T-cells after transplantation (p<0.05). In addition, KTRs developing NODAT showed an increase in alloreactive T-cells during the first months after transplantation (p<0.05).

Our results suggest an increased risk for infection and sepsis in KTRs with pre-existing diabetes and NODAT possibly with hyperglycemia altering overall immunity. High rates of CMV infection in KTRs with NODAT may contribute to the increase in alloreactive T-cells and high rates of acute rejection episodes. Since higher rates of acute rejection, but not pre-existing diabetes or NODAT were associated with lower allograft survival and eGFR, maintaining adequate immunosuppression to prevent rejection, even at the expense of the development of NODAT seems of major importance.

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