Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apnea (OSA) is associated with an enhanced systemic inflammation and oxidative stress, but mechanisms that regulate these processes are poorly understood. The aim of the study was to investigate the plasma levels of klotho in OSA. Twenty-one previously untreated patients with OSA (56 +/- 13 years, 12 males) and 41 non-OSA control volunteers (48 +/- 16 years, 8 males) participated in the study. Medical history has been taken; participants filled out the Epworth Sleepiness Scale. C-reactive protein and renal function, glucose and lipid profile measurements were performed in sera; klotho was determined in citrate-treated plasma samples. Levels of plasma klotho were decreased in OSA (519.1 +/- 164.9 pg/mL) versus controls (700.8 +/- 431.4 pg/mL, p = 0.02). Reduced klotho concentrations were associated with markers of overnight hypoxemia determined with O-2 desaturation index (r = -0.31, p = 0.01), percentage of sleep time spent with saturation <90% (r = -0.41, p < 0.01), and minimal saturation during sleep (r = 0.33, p = 0.01). Interestingly, there was no relationship with apnea-hypopnea index, total sleep time, or arousal index (all p > 0.05). Significant association was also found between low plasma klotho levels and the presence of hypertension (p < 0.05). Our results suggest that chronic intermittent hypoxia reduces the levels of klotho in OSA, which may contribute to the development of hypertension. Decreased klotho levels may play a role in enhanced systemic inflammation in OSA and may be a future target for drug development.