Low Dietary Bromide Intake and Sex-Specific Mortality in Kidney Transplant Recipients

Low bromide intake may be a modifiable risk factor for reduced survival among kidney transplant recipients (KTRs).

We investigated dietary determinants of 24-h urinary bromide excretion and examined the association between 24-h urinary bromide excretion and mortality. Given potential sex differences, additional sex-stratified analyses were performed.

Adult KTRs from the TransplantLines Food & Nutrition Biobank and Cohort Study were included. Dietary determinants of urinary bromide excretion were assessed with multivariable linear regression. Associations of 24-h urinary bromide excretion were evaluated using multivariable sex-stratified Cox regression analyses.

The study included 693 KTRs (43% female; mean age 53 ± 13 y). Urinary bromide excretion was lower in females than in males [median: 2958 (IQR: 2343-3713)] compared with median: 3640 [IQR: 2853-4585] μg/24 h; P < 0.001}. Energy intake (β = 0.12, P = 0.002), animal protein intake (β = 0.16, P = 0.001), and water intake (β = 0.13, P = 0.005) were positively associated with urinary bromide excretion. In sex-stratified analyses, animal protein intake was a significant determinant of bromide excretion in females (β = 0.22, P = 0.002), whereas water (β = 0.15, P = 0.02) and energy intake (β = 0.13, P = 0.01) were associated with bromide excretion in males. During a median follow-up of 5.3 (IQR: 4.8-6.1) years, 150 KTRs (21.6%) died. Higher urinary bromide excretion was consistently associated with a lower risk of mortality, even after adjustment for potential confounders [hazard ratio [HR]: 0.67 [95% confidence interval (CI): 0.50, 0.90]; P = 0.008]. The association of urinary bromide excretion with mortality was significantly modified by sex (P _interaction = 0.02). Among females, there was a significant independent association between higher urinary bromide excretion and lower mortality [HR: 0.45 (95% CI: 0.29;0.72), P = 0.001], whereas no such association was observed in males.

Energy, animal protein, and water intake were positively associated with urinary bromide excretion, with sex-specific differences. Lower urinary bromide excretion was independently associated with increased all-cause mortality in female, but not in male KTRs. These findings support further investigation into whether improving bromide status could reduce mortality, particularly among female KTRs.This trial was registered at clinicaltrials.gov as NCT02811835.