Meta-Analysis

. 2023 Jan 18:380:e072909.

doi: 10.1136/bmj-2022-072909.

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts

Kwok Leung Ong¹, Matti Marklund^{2

3

4}, Liping Huang², Kerry-Anne Rye⁵, Nicholas Hui⁵, Xiong-Fei Pan^{2

6

7}, Casey M Rebholz⁸, Hyunju Kim⁸, Lyn M Steffen⁹, Anniek C van Westing¹⁰, Johanna M Geleijnse¹⁰, Ellen K Hoogeveen^{11

12

13

14}, Yun-Yu Chen, Kuo-Liong Chien¹², Amanda M Fretts¹⁵, Rozenn N Lemaitre¹⁶, Fumiaki Imamura¹⁷, Nita G Forouhi¹⁷, Nicholas J Wareham¹⁷, Anna Birukov^{18

19}, Susanne Jäger^{18

19}, Olga Kuxhaus^{18

19}, Matthias B Schulze^{18

19

20}, Vanessa Derenji de Mello²¹, Jaakko Tuomilehto^{22

23

24}, Matti Uusitupa²¹, Jaana Lindström²², Nathan Tintle^{25

26}, William S Harris^{25

27

28}, Keisuke Yamasaki²⁸, Yoichiro Hirakawa²⁹, Toshiharu Ninomiya²⁸, Toshiko Tanaka³⁰, Luigi Ferrucci³⁰, Stefania Bandinelli³¹, Jyrki K Virtanen²¹, Ari Voutilainen²¹, Tharusha Jayasena³², Anbupalam Thalamuthu³², Anne Poljak³³, Sonia Bustamante^{33

32}, Perminder S Sachdev, Mackenzie K Senn 2nd³⁴, Stephen S Rich^{35

36}, Michael Y Tsai³⁷, Alexis C Wood³⁴, Markku Laakso^{38

39}, Maria Lankinen²¹, Xiaowei Yang⁴⁰, Liang Sun⁴⁰, Huaixing Li⁴⁰, Xu Lin^{40

41}, Christoph Nowak⁴², Johan Ärnlöv⁴², Ulf Risérus⁴, Lars Lind⁴³, Mélanie Le Goff⁴⁴, Cécilia Samieri⁴⁴, Catherine Helmer⁴⁴, Frank Qian^{45

46}, Renata Micha^{47

48}, Adrienne Tin^{8

49}, Anna Köttgen^{8

50}, Ian H de Boer^{51

52

53}, David S Siscovick⁵⁴, Dariush Mozaffarian⁴⁸, Jason Hy Wu^{2

55}

Affiliations

¹ Lipid Research Group, School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia oklws@yahoo.com.hk.
² The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
³ The Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
⁵ Lipid Research Group, School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁶ Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
⁷ Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, China.
⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ University of Minnesota School of Public Health, Minneapolis, MN, USA.
¹⁰ Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
¹¹ Department of Nephrology, Jeroen Bosch Hospital, Den Bosch, The Netherlands.
¹² Institute of Epidemiology and Preventive Medicine College of Public Health, National Taiwan University, Taipei, Taiwan.
¹³ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁴ Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁶ Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁷ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
¹⁹ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
²⁰ Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
²¹ Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.
²² Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
²³ Department of Public Health, University of Helsinki, Helsinki, Finland.
²⁴ Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
²⁵ The Fatty Acid Research Institute, Sioux Falls, SD, USA.
²⁶ Department of Population Health Nursing Science, College of Nursing, University of Illinois-Chicago, Chicago, IL, USA.
²⁷ Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
²⁸ Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁹ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³⁰ Translational Gerontology Branch, National Institute on Aging, National Institute of Health, Baltimore, MD, USA.
³¹ Geriatric Unit, Azienda USL Toscana Centro, Florence, Italy.
³² Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
³³ Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia.
³⁴ USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
³⁵ Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
³⁶ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
³⁷ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
³⁸ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
³⁹ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
⁴⁰ Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁴¹ Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.
⁴² Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Sweden.
⁴³ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁴⁴ Bordeaux Population Health Research Centre, INSERM, UMR 1219, University of Bordeaux, Bordeaux, France.
⁴⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
⁴⁶ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Food Science and Nutrition, University of Thessaly, Karditsa, Greece.
⁴⁸ The Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
⁴⁹ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁰ Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, Germany.
⁵¹ Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
⁵² Kidney Research Institute, University of Washington, Seattle, WA, USA.
⁵³ Puget Sound VA Healthcare System, Seattle, WA, USA.
⁵⁴ New York Academy of Medicine, New York, NY, USA.
⁵⁵ School of Population Health, University of New South Wales, Sydney, NSW, Australia.

PMID: 36653033
PMCID: PMC9846698
DOI: 10.1136/bmj-2022-072909

Meta-Analysis

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts

Kwok Leung Ong et al. BMJ. 2023.

. 2023 Jan 18:380:e072909.

doi: 10.1136/bmj-2022-072909.

Authors

Affiliations

¹ Lipid Research Group, School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia oklws@yahoo.com.hk.
² The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
³ The Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁴ Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
⁵ Lipid Research Group, School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁶ Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
⁷ Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, China.
⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ University of Minnesota School of Public Health, Minneapolis, MN, USA.
¹⁰ Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
¹¹ Department of Nephrology, Jeroen Bosch Hospital, Den Bosch, The Netherlands.
¹² Institute of Epidemiology and Preventive Medicine College of Public Health, National Taiwan University, Taipei, Taiwan.
¹³ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁴ Heart Rhythm Center, Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
¹⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁶ Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁷ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
¹⁸ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
¹⁹ German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
²⁰ Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
²¹ Institute of Public Health and Clinical Nutrition, School of Medicine, University of Eastern Finland, Kuopio, Finland.
²² Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
²³ Department of Public Health, University of Helsinki, Helsinki, Finland.
²⁴ Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
²⁵ The Fatty Acid Research Institute, Sioux Falls, SD, USA.
²⁶ Department of Population Health Nursing Science, College of Nursing, University of Illinois-Chicago, Chicago, IL, USA.
²⁷ Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.
²⁸ Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
²⁹ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
³⁰ Translational Gerontology Branch, National Institute on Aging, National Institute of Health, Baltimore, MD, USA.
³¹ Geriatric Unit, Azienda USL Toscana Centro, Florence, Italy.
³² Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
³³ Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia.
³⁴ USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
³⁵ Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
³⁶ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
³⁷ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
³⁸ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
³⁹ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
⁴⁰ Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁴¹ Key Laboratory of Systems Health Science of Zhejiang Province, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Hangzhou, China.
⁴² Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Sweden.
⁴³ Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁴⁴ Bordeaux Population Health Research Centre, INSERM, UMR 1219, University of Bordeaux, Bordeaux, France.
⁴⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
⁴⁶ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Food Science and Nutrition, University of Thessaly, Karditsa, Greece.
⁴⁸ The Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
⁴⁹ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁰ Institute of Genetic Epidemiology, Department of Data Driven Medicine, Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, Germany.
⁵¹ Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
⁵² Kidney Research Institute, University of Washington, Seattle, WA, USA.
⁵³ Puget Sound VA Healthcare System, Seattle, WA, USA.
⁵⁴ New York Academy of Medicine, New York, NY, USA.
⁵⁵ School of Population Health, University of New South Wales, Sydney, NSW, Australia.

PMID: 36653033
PMCID: PMC9846698
DOI: 10.1136/bmj-2022-072909

Abstract

Objective: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

Design: Pooled analysis.

Data sources: A consortium of 19 studies from 12 countries identified up to May 2020.

Study selection: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

Data extraction and synthesis: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.

Main outcome measures: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m². In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m² and <75% of baseline rate.

Results: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I²=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I²=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I²=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (≥60 v <60 years), estimated glomerular filtration rate (60-89 v ≥90 mL/min/1.73 m²), hypertension, diabetes, and coronary heart disease at baseline.

Conclusions: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest and declare: support from Australian National Health and Medical Research Council Career Development Fellowship and the University of New South Wales Safety Net Fellowship for the submitted work; MM reports research funding from Resolve to Save Lives, World Health Organisation and North western University, and support as invited speaker in the Nordic Dairy Congress 2022. CMR and LMS report research funding from the US National Institute of Health (NIH). CMR reports participation on the Data Safety Monitoring Boards of the SUPER and ADEPT trials and leadership role as associate editor of Diabetes Care. ACvW reports research funding from Jaap Schouten Foundation. JMG reports research funding from Jaap Schouten Foundation, EU Horizon 2020, and Ministry of Health, Welfare and Sports, The Netherlands, and leadership role as the Vice President of the Dutch Health Council. EKH reports research funding from Dutch Kidney Foundation. FI and NGF receive the MRC Epidemiology Unit core support. NGF reports research fundings from the NIHR Cambridge Biomedical Research Centre Theme on Nutrition, Diet and Lifestyle. JT declares conference support from the University of Antioquia, Colombia and possession of stocks from Orion Pharma. MU declares possession of stocks from Orion Pharma. WSH declares possession of stock in OmegaQuant Analytics, LLC (a laboratory that offers blood fatty acid testing to healthcare providers, researchers and consumers). PSS reports research funding from the National Health and Medical Research Council of Australia and honoraria from Biogen Australia and Roche Australia. ACW reports research funding from the US Department of Agriculture/Agricultural Research Service, NIH, National Cattlemen’s Beef Association and Hass Avocado Board Avocado Nutrition Research Center. JA has received research honoraria for lectures from AstraZeneca and Novartis, and has participated in the advisory board for AstraZeneca and Boerhinger Ingelheim, unrelated to the present study. UR reports research funding from Swedish Research Council Forma and Swedish Diabetes Foundation. RM reports research funding from the US NIH, Gates Foundation, Nestle and Danone, and consulting fees from Development Initiatives with leadership role as chair of the Independent Expert Group, Global Nutrition Report. AT declares as co-chair of ClinGen Gout Genetic Curation Panel and reports research funding from the US National Institute of Health; AK reports research funding from the German Research Foundation. DM reports research funding from the US NIH, the Gates Foundation, The Rockefeller Foundation, Vail Innovative Global Research, and the Kaiser Permanente Fund at East Bay Community Foundation; personal fees from Acasti Pharma and Barilla; scientific advisory board, Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart, January Inc., Perfect Day, Tiny Organics, and (ended) Day Two, Discern Dx, and Season Health; stock ownership in Calibrate and HumanCo; and chapter royalties from UpToDate. No other relationships or activities that could appear to have influenced the submitted work were reported.

Figures

**Fig 1**
Association of total seafood n-3 PUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident CKD. Incident CKD was defined as an eGFR<60 mL/min/1.73 m² during follow-up among participants with baseline eGFR≥60 mL/min/1.73 m². Analyses were adjusted for age, sex, race, field centre if applicable, education, occupation, body mass index, smoking, physical activity, alcohol intake, prevalent coronary heart disease, and use of lipid lowering drugs. Study specific estimates per interquintile range (difference between midpoint of lowest fifth and highest fifth) of total n-3 PUFAs were pooled separately for different lipid compartments and overall. AOC=Alpha Omega Cohort; ARIC=Atherosclerosis Risk in Communities Study; CCCC=Chin-Shan Community Cardiovascular Cohort Study; CHS=Cardiovascular Health Study; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; EPIC-Norfolk=European Prospective Investigation into Cancer and Nutrition (Norfolk); EPIC-Potsdam=European Prospective Investigation into Cancer and Nutrition (Potsdam); FDPS=Finnish Diabetes Prevention Study; FHS=Framingham Heart Study; InCHIANTI=Invecchiare in Chianti Study; KIHD=Kuopio Ischaemic Heart Disease Risk Factor Study; MAS=Memory and Ageing Study; MESA=Multi-Ethnic Study of Atherosclerosis; METSIM=Metabolic Syndrome in Men; n-3 PUFA=omega 3 polyunsaturated fatty acid; NHAPC=Nutrition and Health of Ageing Populations in China; PIVUS=Prospective Investigation of the Vasculature in Uppsala Seniors; WHIMS=Women’s Health Initiative Memory Study; ULSAM=Uppsala Longitudinal Study of Adult Men; 3C=Three City Study

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References

1. Hill NR, Fatoba ST, Oke JL, et al. . Global prevalence of chronic kidney disease–a systematic review and meta-analysis. PLoS One 2016;11:e0158765. 10.1371/journal.pone.0158765 - DOI - PMC - PubMed
1. GBD Chronic Kidney Disease Collaboration . Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020;395:709-33. 10.1016/S0140-6736(20)30045-3 - DOI - PMC - PubMed
1. Matsushita K, Coresh J, Sang Y, et al. CKD Prognosis Consortium . Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol 2015;3:514-25. 10.1016/S2213-8587(15)00040-6 - DOI - PMC - PubMed
1. Hoogeveen EK, Geleijnse JM, Giltay EJ, et al. . Kidney function and specific mortality in 60-80 years old post-myocardial infarction patients: a 10-year follow-up study. PLoS One 2017;12:e0171868. 10.1371/journal.pone.0171868 - DOI - PMC - PubMed
1. King-Wing Ma T, Kam-Tao Li P. Depression in dialysis patients. Nephrology (Carlton) 2016;21:639-46. 10.1111/nep.12742 - DOI - PubMed

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Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts

Affiliations

Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts

Authors

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Conflict of interest statement

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