Publications

Introduction

Patients on hemodialysis experience a heavy burden of symptoms that may be related to the low levels of physical activity reported in this population. We hypothesized that physical activity would be inversely related to symptom severity and that depression might mediate this association.

Methods

We designed a cross-sectional study of 48 patients receiving hemodialysis at 3 San Francisco dialysis clinics. Physical activity was measured using pedometers and recorded within 1 week of symptom assessment. Symptoms were assessed using total symptom burden and severity on the Dialysis Symptom Index (DSI; burden 0-29, severity 0-145), individual symptoms on the DSI (0-5), Kidney Disease Quality of Life Vitality scores, (0-100), and the Center for Epidemiologic Study-Depression (0-60).

Results

Median daily step count was 2631 (25th, 75th percentile 1125, 5278). Seventy-three percent of patients reported fatigue. After adjustment for age, sex, diabetes, and serum albumin, physical activity was associated with 0.2 points lower fatigue severity per 1000 steps per day (95% confidence interval [CI] -0.3 to 0.0), = 0.04. Physical activity was also associated with higher Vitality score (2.36 points per 1000 steps; 95% CI 0.07-4.65) and lower insomnia scores (-0.1 points per 1000 steps; 95% CI -0.3 to 0.0], < 0.05) in our adjusted models. Physical activity was not associated with other symptoms.

Conclusion

Because the study was cross-sectional, we cannot determine whether physical activity lowers fatigue and insomnia or whether less insomnia and fatigue increase physical activity. However, interventions to increase physical activity should be considered alongside current strategies as a possible approach to managing fatigue and insomnia.

Natural killer (NK) cells are innate lymphoid cells that have been increasingly recognised as important in lung allograft tolerance and immune defence. These cells evolved to recognise alterations in self through a diverse set of germline-encoded activating and inhibitory receptors and display a broad range of effector functions that play important roles in responding to infections, malignancies and allogeneic tissue. Here, we review NK cells, their diverse receptors and the mechanisms through which NK cells are postulated to mediate important lung transplant clinical outcomes. NK cells can promote tolerance, such as through the depletion of donor antigen-presenting cells. Alternatively, these cells can drive rejection through cytotoxic effects on allograft tissue recognised as 'non-self' or 'stressed', via killer cell immunoglobulin-like receptor (KIR) or NKG2D receptor ligation, respectively. NK cells likely mediate complement-independent antibody-mediated rejection of allografts though CD16A Fc receptor-dependent activation induced by graft-specific antibodies. Finally, NK cells play an important role in response to infections, particularly by mediating cytomegalovirus infection through the CD94/NKG2C receptor. Despite these sometimes-conflicting effects on allograft function, enumeration of NK cells may have an important role in diagnosing allograft dysfunction. While the effects of immunosuppression agents on NK cells may currently be largely unintentional, further understanding of NK cell biology in lung allograft recipients may allow these cells to serve as biomarkers of graft injury and as therapeutic targets.