Yukinobu Kuwamura1, Tetsuo Shoji2, Yujiro Okute1, Yuko Yamazaki1, Koka Motoyama1, Tomoaki Morioka1, Katsuhito Mori3, Shinya Fukumoto4, Yoshihiro Tsujimoto5, Atsushi Shioi6, Masanori Emoto1, Masaaki Inaba7. 1. Department of Metabolism, Endocrinology and Molecular Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. 2. Department of Vascular Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; Vascular Science Center for Translational Research, Graduate School of Medicine, Osaka City University, Osaka, Japan. Electronic address: t-shoji@med.osaka-cu.ac.jp. 3. Department of Nephrology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 4. Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan. 5. Division of Internal Medicine, Dialysis Center, Inoue Hospital, Suita, Osaka, Japan. 6. Department of Vascular Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; Vascular Science Center for Translational Research, Graduate School of Medicine, Osaka City University, Osaka, Japan. 7. Department of Metabolism, Endocrinology and Molecular Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; Vascular Science Center for Translational Research, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Abstract
OBJECTIVE: Alterations in the balance between serum n-3 and n-6 polyunsaturated fatty acids (PUFAs) is predictive of cardiovascular events among hemodialysis patients, although little is known about the serum ratio of n-6 arachidonic acid (AA) to n-6 dihomo-γ-linoleic acid (DGLA) in renal failure. We hypothesized that AA/DGLA ratio is altered in hemodialysis patients resulting in poor clinical outcomes. METHODS: This was a single center cohort study in an urban area in Japan with cross-sectional analyses. Subjects were 517 hemodialysis patients and 122 control subjects. The main exposure was serum AA/DGLA ratio, and the main outcome measures were all-cause mortality and cardiovascular events during 5 years. RESULTS: The hemodialysis patients showed a higher median (interquartile range) AA/DGLA ratio than the control subjects (6.46 [5.22-7.81] versus 4.56 [3.74-6.34], P < .001). In a Cox proportional hazard model adjusted for age, sex, dialysis duration, diabetic nephropathy, prior cardiovascular disease, and the ratio of serum n-3 polyunsaturated fatty acids (eicosapentaenoic acid plus docosahexaenoic acid) to AA, the higher quartiles of AA/DGLA ratio were associated with higher risk for all-cause mortality with hazard ratios (95% confidence interval) of 1.50 (0.84-2.76) for quartile 2, 2.10 (1.18-3.86) for quartile 3, and 2.02 (1.10-3.78) for quartile 4 compared with quartile 1. AA/DGLA ratio showed a similar association with the risk of cardiovascular events. CONCLUSIONS: AA/DGLA ratio was elevated in patients with end-stage renal disease requiring hemodialysis, and a high AA/DGLA ratio was an independent predictor of poor clinical outcomes in this population.
OBJECTIVE: Alterations in the balance between serum n-3 and n-6 polyunsaturated fatty acids (PUFAs) is predictive of cardiovascular events among hemodialysis patients, although little is known about the serum ratio of n-6 arachidonic acid (AA) to n-6 dihomo-γ-linoleic acid (DGLA) in renal failure. We hypothesized that AA/DGLA ratio is altered in hemodialysis patients resulting in poor clinical outcomes. METHODS: This was a single center cohort study in an urban area in Japan with cross-sectional analyses. Subjects were 517 hemodialysis patients and 122 control subjects. The main exposure was serum AA/DGLA ratio, and the main outcome measures were all-cause mortality and cardiovascular events during 5 years. RESULTS: The hemodialysis patients showed a higher median (interquartile range) AA/DGLA ratio than the control subjects (6.46 [5.22-7.81] versus 4.56 [3.74-6.34], P < .001). In a Cox proportional hazard model adjusted for age, sex, dialysis duration, diabetic nephropathy, prior cardiovascular disease, and the ratio of serum n-3 polyunsaturated fatty acids (eicosapentaenoic acid plus docosahexaenoic acid) to AA, the higher quartiles of AA/DGLA ratio were associated with higher risk for all-cause mortality with hazard ratios (95% confidence interval) of 1.50 (0.84-2.76) for quartile 2, 2.10 (1.18-3.86) for quartile 3, and 2.02 (1.10-3.78) for quartile 4 compared with quartile 1. AA/DGLA ratio showed a similar association with the risk of cardiovascular events. CONCLUSIONS: AA/DGLA ratio was elevated in patients with end-stage renal disease requiring hemodialysis, and a high AA/DGLA ratio was an independent predictor of poor clinical outcomes in this population.
Authors: Tong Liu; Inci Dogan; Michael Rothe; Jana Reichardt; Felix Knauf; Maik Gollasch; Friedrich C Luft; Benjamin Gollasch Journal: Metabolites Date: 2022-03-21