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Item The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma(MDPI, 2020-06-17) Kays, Joshua K.; Koniaris, Leonidas G.; Cooper, Caleb A.; Pili, Roberto; Jiang, Guanglong; Liu, Yunlong; Zimmers, Teresa A.; Medical and Molecular Genetics, School of MedicineClear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA). Skeletal muscle and fat masses measured from CT scans and tumor cytokine gene expression were compared with survival by univariate and multivariate analysis. Patients in the lowest skeletal muscle mass (SKM) quartile had significantly shorter overall survival versus the top three SKM quartiles. Patients who fell into the lowest quartiles for visceral adipose mass (VAT) and subcutaneous adipose mass (SCAT) also demonstrated significantly shorter overall survival. Multiple tumor cytokines correlated with mortality, most strongly interleukin-6 (IL-6); high IL-6 expression was associated with significantly decreased survival. The combination of low SKM/high IL-6 was associated with significantly lower overall survival compared to high SKM/low IL-6 expression (26.1 months vs. not reached; p < 0.001) and an increased risk of mortality (HR = 5.95; 95% CI = 2.86–12.38). In conclusion, tumor cytokine expression, body composition, and survival are closely related, with low SKM/high IL-6 expression portending worse prognosis in ccRCC.Item A longitudinal study of the effects of age, sex and race on body composition in chronic kidney disease(Oxford University Press, 2019-03-07) Agarwal, Rajiv; Medicine, School of MedicineBackground Chronic kidney disease (CKD) is characterized by accelerated aging, but the age-related changes in body composition and its modification by sex and race are unclear. Methods We assembled a cohort of 516 patients with CKD and 45 healthy controls and serially measured body composition using air-displacement plethysmography for up to 6 years. Mixed models were used to evaluate simultaneously the baseline and longitudinal changes in body composition as influenced by age, sex and race. Results Compared with healthy controls, patients with CKD had a greater weight, body mass index (BMI), fat mass (FM) and percent body fat (BF%), but the changes over time in body composition were similar. Older age (>60 years) was a strong determinant of loss of weight, BMI, FM and fat-free mass (FFM), but not BF%. Compared with non-blacks, blacks had a higher FFM at baseline, but they lost FFM more rapidly. Compared with women, men had an accelerated loss of FFM and accumulation of FM. Taking interactions into account, we found that young black men had no significant change in weight due to the loss of FFM and the accumulation of FM, thereby masking obesity by conventional measurements. Conclusion Among patients with CKD, the changes in body composition are influenced by age, sex and race. Young black men have changes in body composition that may remain undetectable by conventional methods thus masking the occurrence of obesity.