Sex and race differences in urinary Tumor Necrosis Factor-α (TNF-α) levels: Secondary analysis of the DASH-sodium trial

Previous work in mouse models shows that urinary TNF-alpha levels become elevated when dietary salt (NaCl) intake increases. To examine if this relationship exists in humans, we conducted a secondary analysis of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine levels of urinary TNF-alpha in 367 subjects categorized by race, sex, and blood pressure. The DASH-Sodium trial is a multicenter feeding trial in which subjects were randomly assigned to either the DASH or control diet, and high, medium, and low sodium in random order. Multivariable linear regression was used to model baseline TNF-alpha and a mixed model was used to model TNF-alpha as a function of dietary intervention. At baseline, with all subjects on a "typical American diet", urinary TNF-alpha levels were lowest in Black, p = 0.002 and male subjects, p < 0.001. After randomization to either the DASH or control diet, with increasing levels of sodium, urinary TNF-alpha levels increased only in subjects on the control diet, p < 0.05. As in the baseline analysis, TNF-alpha levels were highest in White females, then White males, Black females and lowest in Black males. The results indicate that urinary TNF-alpha levels in DASH-Sodium subjects are regulated by NaCl intake, modulated by the DASH diet, and influenced by both race and sex. The inherent differences between subgroups support studies in mice showing that increases in renal TNF-alpha minimize the extent salt-dependent activation of NKCC2.