• Jun Morinaga, Tatsuyuki Kakuma, Hirotaka Fukami, Manabu Hayata, Kohei Uchimura, Teruhiko Mizumoto, Yutaka Kakizoe, Taku Miyoshi, Naoki Shiraishi, Masataka Adachi, Yuichiro Izumi, Takashige Kuwabara, Yusuke Okadome, Michio Sato, Haruki Horiguchi, Taichi Sugizaki, Tsuyoshi Kadomatsu, Keishi Miyata, Saeko Tajiri, Tetsuya Tajiri, Kimio Tomita, Kenichiro Kitamura, Yuichi Oike, and Masashi Mukoyama.
• Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
• Nephrol. Dial. Transplant. 2020 May 1; 35 (5): 854-860.

BackgroundPatients undergoing hemodialysis treatment have a poor prognosis, as many develop premature aging. Systemic inflammatory conditions often underlie premature aging phenotypes in uremic patients. We investigated whether angiopoietin-like protein 2 (ANGPTL 2), a factor that accelerates the progression of aging-related and noninfectious inflammatory diseases, was associated with increased mortality risk in hemodialysis patients.MethodsWe conducted a multicenter prospective cohort study of 412 patients receiving maintenance hemodialysis and evaluated the relationship between circulating ANGPTL2 levels and the risk for all-cause mortality. Circulating ANGPTL2 levels were log-transformed to correct for skewed distribution and analyzed as a continuous variable.ResultsOf 412 patients, 395 were included for statistical analysis. Time-to-event data analysis showed high circulating ANGPTL2 levels were associated with an increased risk for all-cause mortality after adjustment for age, sex, hemodialysis vintage, nutritional status, metabolic parameters and circulating high-sensitivity C-reactive protein levels {hazard ratio [HR] 2.04 [95% confidence interval (CI) 1.10-3.77]}. High circulating ANGPTL2 levels were also strongly associated with an increased mortality risk, particularly in patients with a relatively benign prognostic profile [HR 3.06 (95% CI 1.86-5.03)]. Furthermore, the relationship between circulating ANGPTL2 levels and mortality risk was particularly strong in patients showing few aging-related phenotypes, such as younger patients [HR 7.99 (95% CI 3.55-18.01)], patients with a short hemodialysis vintage [HR 3.99 (95% CI 2.85-5.58)] and nondiabetic patients [HR 5.15 (95% CI 3.19-8.32)].ConclusionWe conclude that circulating ANGPTL2 levels are positively associated with mortality risk in patients receiving maintenance hemodialysis and that ANGPTL2 could be a unique marker for the progression of premature aging and subsequent mortality risk in uremic patients, except those with significant aging-related phenotypes.© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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