Sehoon Park1,2, Soojin Lee3,4, Yaerim Kim5, Yeonhee Lee3,4, Min Woo Kang3,4, Kwangsoo Kim6, Yong Chul Kim3, Seung Seok Han3,7, Hajeong Lee3, Jung Pyo Lee3,7,8, Kwon Wook Joo3,4,7, Chun Soo Lim3,7,8, Yon Su Kim1,3,4,7, Dong Ki Kim3,4,7. 1. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea. 2. Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, Korea. 3. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. 4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. 5. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea. 6. Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea. 7. Kidney Research Institute, Seoul National University, Seoul, Korea. 8. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
Abstract
BACKGROUND: The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes. OBJECTIVES: We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis. METHODS: The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR. RESULTS: The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)]. CONCLUSIONS: A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.
RCT Entities:
BACKGROUND: The effects of specific macronutrients on kidney function independent of total calorie intake have rarely been studied, although the composition of macronutrient intake has been reported to affect health outcomes. OBJECTIVES: We aimed to investigate the effects of macronutrient intake ratios on the risk of chronic kidney disease (CKD) by Mendelian randomization (MR) analysis. METHODS: The study was an observational cohort study mainly based on the UK Biobank and including MR analysis. First, we evaluated the relative baseline macronutrient composition-that is, the number of calories from each macronutrient divided by total calorie intake-of the diets of UK Biobank participants, and we used Cox regression to assess the incidence of end-stage kidney disease (ESKD) in 65,164 participants with normal kidney function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. We implemented a genetic instrument for relative fat, protein, and carbohydrate intake developed by a previous genome-wide association study (GWAS) and performed MR analysis. Two-sample MR was performed with the summary statistics from independent CKDGen GWAS for kidney function traits (n = 567,460), including CKD (eGFR <60 mL/min/1.73 m2) and log-transformed eGFR. RESULTS: The median relative macronutrient intake composition at baseline was 35% fats, 15% protein, and 50% carbohydrates. Higher relative protein intake in subjects with normal kidney function was significantly associated with a lower risk of incident ESKD (HR: 0.54; 95% CI: 0.30, 0.95) in the observational investigation. Two-sample MR indicated that increased relative fat intake causally increased the risk of kidney function impairment [CKD (OR: 1.94; 95% CI: 1.39, 2.71); log eGFR (β: -0.036; 95% CI: -0.048, -0.024)] and that higher relative protein intake was causally linked to a lower CKD risk [CKD (OR: 0.50; 95% CI: 0.35, 0.72); log eGFR (β: 0.044; 95% CI: 0.030, 0.058)]. CONCLUSIONS: A desirable macronutrient composition, including high relative protein intake and low relative fat intake, may causally reduce the risk of CKD in the general population.