Significantly increased morbidity and mortality with the chronic idiopathic hypophosphatemia in Korea

초록

Epidemiologic studies of hypophosphatemia originated from non-secondary and non-renal causes are limited worldwide due to the rarity. Therefore, we aimed to identi-fy the prevalence and long-term health outcomes in patients with hypophosphatemia. This nation-wide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of hypophosphatemia, initially diag-nosed from 2003 to 2018. Among the entire Korean population, we identified 154 patients (76 men and 78 women) diagnosed with non-secondary and non-renal hypophosphatemia after excluding possible secondary conditions which can change serum phosphorus level including Fanconi syndrome, hypoparathyroidism, hyperparathyroidism, renal tubular dis-eases, chronic kidney diseases, and post-thyroidectomy status. We hypothesized that patients who met inclusion criteria might have fibroblast growth factor 23 (FGF23) related hypophs-phatemic disease including X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). These hypophosphatemic patients were compared at a 1:10 ratio, with age-, sex-, and index year- matched controls (n=1,540). The age-standardized incidence rate showed a slightly increasing or stationary trend from 0.24 per 1,000,000 persons in 2003 to 0.30 in 2018. Hypophosphatemic patients were at elevated risk for heart failure (adjust-ed hazard ratio [aHR], 3.83; 95% confidence interval [CI], 1.36 to 10.83), chronic kidney disease (aHR, 15.24; 95% CI, 7.40 to 31.38), hyperparathyroidism (aHR, 126.40; 95% CI, 16.58 to 963.74), periodontitis (aHR, 6.85; 95% CI, 1.53 to 30.59), enthesopathy (aHR, 1.80; 95% CI, 1.02 to3.19), depression (aHR, 1.74; 95% CI, 1.02 to 3.00), and anxiety (aHR, 1.62; 95% CI, 1.02 to 2.58) compared to their controls. Hypophosphatemic patients were also at higher risks of mortality and hospitalization than their controls (aHR, 5.56; 95% CI, 3.58 to 9.42 and aHR, 2.26; 95% CI 1.82 to 2.81, respectively). In conclusion, this is the first epi-demiological survey of non-secondary and non-renal hypophosphatemia to reveal its preva-lence and prognosis in South Korea. According to our findings, patients with hypophospha-temia had higher risks for various complications and mortality. Therefore, early detection and comprehensive management should be necessary to improve their lifelong outcomes.