Serum klotho reduction ups death risk in persons with vitamin D deficiency

A decreasing klotho, a biomarker of vitamin D activation and metabolism, plays a key role in the association between 25-hydroxyvitamin D (25[OH]D) and mortality, reveals a study. This finding suggests that a disruption in vitamin D metabolism leads to an increased risk of death.

This study included a total of 9,870 adults from the National Health and Nutrition Examination Survey (2007‒2016). Investigators validated the mortality data by linking participants to National Death Index records. Finally, they examined the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality.

The findings revealed a significant interaction between klotho and serum 25(OH)D in all-cause mortality (p=0.028). No significant all-cause and CVD mortality risk was observed with klotho >848.4 pg/mL (risk threshold on mortality) at any serum 25(OH)D level.

However, there was a higher all-cause and CVD mortality risk seen with klotho <848.4 pg/mL at serum 25(OH)D <50 nmol/L (all-cause death: hazard ratio [HR], 1.36, 95 percent confidence interval [CI], 1.10‒1.69; CVD death: HR, 1.78, 95 percent CI, 1.16‒3.45) and serum 25(OH)D of continuous variable (HR, 0.98, 95 percent CI, 0.97‒0.99 and HR, 0.98, 95 percent CI, 0.98‒0.99, respectively).

Furthermore, vitamin D metabolism dysfunction accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) led to increased risks of all-cause (HR, 1.48, 95 percent CI, 1.11‒1.96) and CVD mortality (HR, 2.36, 95 percent CI, 1.48‒3.75).

“Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency,” the investigators said.