Obesity has been associated with an increased risk of graft loss and death after kidney transplantation. The role of cellular immunity in obese kidney transplant recipients (KTRs), however, hasn't been addressed so far.

Here, we studied all KTRs transplanted between 2005 and 2012. 29 (4%), 317 (48%), 217 (33%), 76 (12%), and 21 KTRs (4%) were identified as underweight, normal-weight, overweight, obese, and morbid obese, respectively. 33 of 97 KTRs (34%) with obesity had pre-existing or new-onset diabetes. A control group of normal-weight KTRs with and without diabetes was used for comparison. Samples were collected before and at +1, +2, +3 months after transplantation. Alloreactive T-cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by lymphocyte subpopulations.

Upon multivariate analysis obese KTRs showed an increased incidence of pre-existing and new-onset diabetes, and DGF (p<0.05). Morbid obese KTRs showed significantly decreased patient survival (p<0.001), but no differences in graft survival (p=0.545). Among obese KTRs, those with diabetes showed decreased patient and graft survial, and higher rates of infection and DGF (p<0.05). Interestingly, no differences were observed between obese KTRs without diabetes and normal-weight KTRs with/without diabetes with respect to patient and graft survival (p>0.05). Obese KTRs showed a state of obesity-related inflammation with signficantly increased CD3+, CD4+, CD8+, and alloreactive T-cells pretransplantation (p<0.05). Interestingly, obese KTRs without diabetes showed significantly increased CD4+CD25+ regulatory T-cells compared to obese KTRs with diabetes pretransplantation (p=0.048). At +1 month obese KTRs with diabetes showed the strongest decline in T-cell counts with significantly lower CD3+, CD4+, CD8+ T-cells compared to obese KTRs without diabetes (p<0.05). No differences were observed between obese KTRs without diabetes and normal-weight KTRs (p>0.05).

Our results suggest that the increased risk for graft loss and death from infection in obese KTRs is limited to those with diabetes. Here, a state of obesity-related inflammation plus hyperglycemia may predispose those to a higher susceptibility to immunosuppression resulting in cellular immune deficits and impaired infection control. Increased alloreactivity in obesity should call for adequate immunosuppression even at the expense of the development of diabetes.

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