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

Abstract

Previous work in mouse models shows that urinary TNF-α 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-α 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-α and a mixed model was used to model TNF-α as a function of dietary intervention. At baseline, with all subjects on a “typical American diet”, urinary TNF-α 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-α levels increased only in subjects on the control diet, p < 0.05. As in the baseline analysis, TNF-α levels were highest in White females, then White males, Black females and lowest in Black males. The results indicate that urinary TNF-α 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-α minimize the extent salt-dependent activation of NKCC2.

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Fig. 1: Study design of the DASH-sodium trial and urine samples available for TNF-α measurement.
Fig. 2: Unadjusted baseline levels of urinary TNF-α by race and sex.
Fig. 3: Adjusted baseline differences in urinary TNF-α levels according to sex and race.
Fig. 4: Adjusted levels of urinary TNF-α among subjects randomized to the control diet (Low to High Sodium) and DASH diet low to high sodium).

Data availability

The data that support the findings of this study are available from NHLBI and BioLINCC but restrictions apply to the availability of these data. Data are however available from the authors upon reasonable request and with permission of NHLBI and BioLINCC.

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Acknowledgements

We acknowledge NHLBI and BioLINCC for access to the DASH-Sodium Trial dataset and samples his work was supported by NIH grants R21HL140260 and R01HL133077.

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Contributions

1. Conceived and designed the analysis. 2. Collected the data. 3. Contributed data or analysis tools. 4. Performed the analysis. 5. Wrote the paper. 6. Other contribution ED (3,4,5). KF (2,3,4). RA (5 – rewriting & editing). HZ (2, 3). NS (6 –statistical consultation) LG (1 – concept development). SH (1 – concept development). NF (1,5).

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Correspondence to Nicholas R. Ferreri.

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Competing interests

Dr. Nancy Stambler is a full-time employee and shareholder of Progenics Pharmaceuticals, a subsidiary of Lantheus Holdings, Inc. Rozalia Abramov is a full-time employee of Eisai, Inc. For the remaining authors none were declared.

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Drugge, E.D., Farhan, K., Zhao, H. et al. Sex and race differences in urinary Tumor Necrosis Factor-α (TNF-α) levels: Secondary analysis of the DASH-sodium trial. J Hum Hypertens (2022). https://doi.org/10.1038/s41371-022-00748-z

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