Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts
Authors: Ong Kwok Leung , Marklund Matti , Huang Liping , Rye Kerry-Anne , Hui Nicholas , Pan Xiong-Fei , Rebholz Casey M , Kim Hyunju , Steffen Lyn M , van Westing Anniek C , Geleijnse Johanna M , Hoogeveen Ellen K , Chen Yun-Yu , Chien Kuo-Liong , Fretts Amanda M , Lemaitre Rozenn N , Imamura Fumiaki , Forouhi Nita G , Wareham Nicholas J , Birukov Anna , Jäger Susanne , Kuxhaus Olga , Schulze Matthias B , de Mello Vanessa Derenji , Tuomilehto Jaakko , Uusitupa Matti , Lindström Jaana , Tintle Nathan , Harris William S , Yamasaki Keisuke , Hirakawa Yoichiro , Ninomiya Toshiharu , Tanaka Toshiko , Ferrucci Luigi , Bandinelli Stefania , Virtanen Jyrki K , Voutilainen Ari , Jayasena Tharusha , Thalamuthu Anbupalam , Poljak Anne , Bustamante Sonia , Sachdev Perminder S , Senn Mackenzie K , Rich Stephen S , Tsai Michael Y , Wood Alexis C , Laakso Markku , Lankinen Maria , Yang Xiaowei , Sun Liang , Li Huaixing , Lin Xu , Nowak Christoph , Ärnlöv Johan , Risérus Ulf , Lind Lars , Le Goff Mélanie , Samieri Cécilia , Helmer Catherine , Qian Frank , Micha Renata , Tin Adrienne , Köttgen Anna , de Boer Ian H , Siscovick David S , Mozaffarian Dariush , Wu Jason HY 
Published: January 2023

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 m
2
. In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m
2
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, I
2
=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, I
2
=0.0%). Plant derived α linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I
2
=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 m
2
), 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.