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

Authors: ONG, KWOK - University Of New South Wales; MARKLUND, MATTI - University Of New South Wales; HUANG, LIPING - University Of New South Wales; RYE, KERRY - University Of New South Wales; HUI, NICHOLAS - University Of New South Wales; PAN, XIONG - University Of New South Wales; REBHOLZ, CASEY - Johns Hopkins School Of Public Health; KIM, HYUNJU - Johns Hopkins School Of Public Health; STEFFAN, LYN - University Of Minnesota; VAN WESTING, ANNIEK - Wageningen University; GELEIJNSE, JOHANNA - Wageningen University; HOOGEVEEN, ELLEN - Non ARS Employee; CHEN, YUN - National Taiwan University; CHIEN, KUO - National Taiwan University; FRETTS, AMANDA - University Of Washington; LEMAITRE, ROZENN - University Of Washington; IMAMURA, FUMIAKI - University Of Cambridge; FOROUHI, NITA - University Of Cambridge; WAREHAM, NICHOLAS - University Of Cambridge; BIRUKOV, ANNA - German Institute Of Human Nutrition; JÄGER, SUSANNE - German Institute Of Human Nutrition; KUXHAUS, OLGA - German Institute Of Human Nutrition; SCHULZE, MATTHIAS - German Institute Of Human Nutrition; DERENJI DE MELLO, VANESSA - University Of Eastern Finland; TUOMILEHTO, JAAKKO - Finnish Institute For Health And Welfare; UUSITUPA, MATTI - University Of Eastern Finland; LINDSTRÖM, JAANA - Finnish Institute For Health And Welfare; TINTLE, NATHAN - Fatty Acid Research Institute; HARRIS, WILLIAM - Fatty Acid Research Institute; YAMASAKI, KEISUKE - Kyushu University; HIRAKAWA, YOICHIRO - Kyushu University; NINOMIYA, TOSHIHARU - Kyushu University; TANAKA, TOSHIKA - National Institute On Aging (NIA, NIH); FERRUCCI, LUIGI - National Institute On Aging (NIA, NIH); BANDINELLI, STEFANIA - Non ARS Employee; VIRTANEN, JYRKI - University Of Eastern Finland; VOUTILAINEN, ARI - University Of Eastern Finland; JAYASENA, THARUSHA - University Of New South Wales; THALAMUTHU, ANBUPALAM - University Of New South Wales; POLJAK, ANNE - University Of New South Wales; BUSTAMANTE, SONIA - University Of New South Wales; SACHDEV, PERMINDER - University Of New South Wales; SENN, MACKENZIE - Children'S Nutrition Research Center (CNRC); RICH, STEPHEN - University Of Virginia; TSAI, MICHAEL - University Of Minnesota; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); LAAKSO, MARKKU - University Of Eastern Finland; LANKINEN, MARIA - University Of Eastern Finland; YANG, XIAOWEI - Chinese Academy Of Sciences; SUN, LIANG - Chinese Academy Of Sciences; LI, HUAIXING - Chinese Academy Of Sciences; LIN, XU - Chinese Academy Of Sciences; NOWAK, CHRISTOPH - Karolinska Institute; ÄRNLÖV, JOHAN - Karolinska Institute; RISÉRUS, ULF - Uppsala University; LIND, LARS - Uppsala University; LE GOFF, MÉLANIE - University Of Bordeaux; SAMIERI, CÉCILIA - University Of Bordeaux; HELMER, CATHERINE - University Of Bordeaux; QIAN, FRANK - Harvard School Of Public Health; MICHA, RENATA - University Of Thessaly; TIN, ADRIENNE - University Of Mississippi Medical Center; KÖTTGEN, ANNA - University Of Freiburg; DE BOER, IAN - University Of Washington; SISCOVICK, DAVID - New York Academy Of Medicine; MOZAFFARIAN, DARIUSH - Friedman School At Tufts; WU, JASON - University Of New South Wales

Submitted to: The BMJ
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/12/2022
Publication Date: 1/18/2023
Citation: Ong, K.L., Marklund, M., Huang, L., Rye, K.A., Hui, N., Pan, X.F., Rebholz, C.M., Kim, H., Steffan, L.M., Van Westing, A.C., Geleijnse, J.M., Hoogeveen, E.K., Chen, Y.Y., Chien, K.L., Fretts, A.M., Lemaitre, R.N., Imamura, F., Forouhi, N.G., Wareham, N.J., Birukov, A., Jäger, S., Kuxhaus, O., Schulze, M.B., Derenji De Mello, V., Tuomilehto, J., Uusitupa, M., Lindström, J., Tintle, N., Harris, W.S., Yamasaki, K., Hirakawa, Y., Ninomiya, T., Tanaka, T., Ferrucci, L., Bandinelli, S., Virtanen, J.K., Voutilainen, A., Jayasena, T., Thalamuthu, A., Poljak, A., Bustamante, S., Sachdev, P.S., Senn, M.K., Rich, S.S., Tsai, M.Y., Wood, A.C., Laakso, M., Lankinen, M., Yang, X., Sun, L., Li, H., Lin, X., Nowak, C., Ärnlöv, J., Risérus, U., Lind, L., Le Goff, M., Samieri, C., Helmer, C., Qian, F., Micha, R., Tin, A., Köttgen, A., De Boer, I.H., Siscovick, D.S., Mozaffarian, D., Wu, J.H. 2023. Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: Pooled analysis of 19 cohorts. The BMJ. 380. Article e072909. https://doi.org/10.1136/bmj-2022-072909.
DOI: https://doi.org/10.1136/bmj-2022-072909

Interpretive Summary: Studies in animals suggest that a type of fatty acids found in many foods, omega-3 polyunsaturated fatty acids (n-3 PUFA) improve kidney function, but evidence from human studies is limited. Most prior studies in humans assessed self-reported intake of n-3 PUFA using people's recollections of how often they ate foods containing n-3 PUFAs, which are subject to errors due to (1) mis-reporting; and (2) inaccuracy within food composition databases used to quantify how much n-3 PUFA was in the foods people reported eating. In the largest analysis to date, among more than 25,000 participants, a biomarker of n-3 PUFA from seafood in blood was associated with a lower risk of developing kidney disease; when people were ordered according to the amount of this biomarker in their blood, those in the top 20% had a 13% lower risk of incident kidney disease compared to those in the bottom 20%. These findings support current USDA guidelines that recommend seafood and oily fish consumption as part of healthy dietary patterns.

Technical Abstract: Our objective was to assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived alpha linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). Design was a pooled analysis. Data sources were a consortium of 19 studies from 12 countries identified up to May 2020. Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate were selected. 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. 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. 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 a 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. 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.