Background: Poor physical performance and frailty are associated with elevated risks of death and disability. Chronic kidney disease (CKD) is also strongly associated with these outcomes. The risks of poor physical performance and frailty among CKD patients, however, are not well established. Methods: We measured the Short Physical Performance Battery (SPPB; a summary test of gait speed, chair raises and balance; range 0-12) and the five elements of frailty among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for demographics and multiple comorbidities, we fit a linear regression model for the outcome of SPPB score and an ordinal logistic regression model for frailty status. Results: Median (interquartile range, IQR) age was 65 (57-71) years, median estimated glomerular filtration rate (eGFR) for non-dialysis patients was 49 (36-62) ml/min/1.73 m², and median SPPB score was 9 (7-10). Seven percent of participants were frail and 43% were pre-frail. Compared with the SPPB score for eGFR >60 ml/min/1.73 m², the SPPB was 0.51 points lower for eGFR 30-59; 0.61 points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty status compared with eGFR >60 ml/min/1.73 m². Conclusions: CKD severity was associated with poor physical performance and frailty in a graded fashion. Future trials should determine if outcomes for CKD patients with frailty and poor physical performance are improved by targeted interventions.

Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.

Low 25-OH-D, common in the paediatric population at risk for diabetes (older children, African-Americans, children with increasing BMI-Z) is associated with worse insulin resistance.