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

Background: Low iodine intake may be a modifiable risk factor for reduced survival among Kidney Transplant Recipients (KTR). Therefore, we performed sex-stratified analyses to examine whether inadequate iodine intake and low 24-hour urinary iodine excretion are associated with increased mortality. Methods: Adult KTR from the Transplant Lines Food and Nutrition Biobank and Cohort Study were included and compared to healthy controls. Associations between 24-hour urinary iodine intake (continuous and classified as inadequate <135 ug/day) with mortality were evaluated using multivariable sex-stratified Cox regression analyses. Results: The study included 624 KTR (43% female, 53±13 years) and 214 healthy controls (49% female, 58±11 years). Among females, inadequate iodine intake was more common (24% vs 6%; P<0.001), and urinary iodine excretion was lower (173 [139–231] vs 265 [216–322] μmol/24h; P<0.001) in KTR than controls. Similar findings were observed among males (inadequate intake: 14% vs 6%, P=0.03; urinary excretion: 211 [161–262] vs 302 [236–361] μmol/24h; P<0.001). During a median follow-up of 5.6 [5.2–6.3] years, 136 (22%) KTR died. The associations of inadequate iodine intake and 24-hour urinary iodine excretion with mortality were modified by sex (P interaction =0.02; P interaction =0.08), respectively. Among female KTR, inadequate iodine intake (HR 3.16 [95%CI: 1.70–5.86]; P<0.001) and lower urinary iodine excretion (HR per halving 1.89 [95%CI: 1.32–2.63]; P<0.001) were both associated with higher mortality in multivariable analyses. In male KTR, inadequate iodine intake and urinary iodine excretion were not associated with increased mortality (both P>0.05). Conclusions: KTR have lower urinary iodine excretion compared to healthy controls, and more frequently fell below the threshold for inadequate iodine intake, particularly among women. Inadequate iodine intake was independently associated with an increased mortality in female, but not in male KTR, underscoring a potential sex-specific vulnerability. These findings support further investigation into whether improving iodine status could reduce mortality, particularly among female KTR.