Exercise In Renal Transplant Recipients: Effects On Circulating Immune And Inflammatory Cells

Renal transplantations are seen to be a double-edge sword. Transplantations help to partially restore renal function, however there are a number of health-related co-morbidities associated with transplantation. Cardiovascular disease (CVD), malignancy and infections all limit patient and graft survival. Immunosuppressive medications alter innate and adaptive immunity and can result in immune dysfunction. Over suppression of the immune system can result in infections whereas under suppression can result in graft rejection. Exercise is a known therapeutic intervention with many physiological benefits. Its effects on immune function are not well characterised and may include both positive and negative influences depending on the type, intensity, and duration of the exercise bout. High intensity interval training (HIIT) has become more popular due to it resulting in improvements to traditional and inflammatory markers of cardiovascular (CV) risk in clinical and non-clinical populations. Though these improvements are similar to those seen with moderate intensity exercise, HIIT requires a shorter overall time commitment, whilst improvements can also be seen even with a reduced exercise volume.

The purpose of this thesis is to explore the physiological and immunological impact of 8-weeks of HIIT and moderate intensity continuous training (MICT) in renal transplant recipients (RTRs). In addition, the natural variations of immune and inflammatory cells in RTRs and healthy controls over a longitudinal period are explored. Newly developed multi-colour flow cytometry methods were devised to identify and characterise immune cell populations. Twenty-six RTRs were randomised into HIIT groups (80-90% V̇O2peak) and MICT (50-60% V̇O2peak; 3x/week over 8

weeks). Physiological outcome measures were conducted, and blood samples taken pre-training, mid training, post-training and 3 months later. Novel multi-colour flow cytometric panels were developed to characterise lymphoid and myeloid cell population from peripheral blood mononuclear cells. Both HIIT and MICT resulted in small physiological adaptations in exercise capacity and physical function and strength measures. However, HIIT groups failed to achieve the exercise intensity. No changes were observed for circulating immune and inflammatory cells over the 8-week interventions. This feasibility study does not suggest that exercise programmes using HIIT and MICT protocols elicit adverse negative effects on immunity in RTRs. Therefore, such protocols may be immunologically safe for these patients. The inability of the participants to achieve the target exercise intensities may be due to physiological abnormalities in this population which warrants further investigation.