Causal associations between polyunsaturated fatty acids and kidney function: A bidirectional Mendelian randomization study

Abstract

Background: PUFAs were suggested to be beneficial for kidney function in observational studies. However, whether these associations are causal remains unclear.

Objectives: This study explores the causality between PUFAs and chronic kidney disease (CKD) or estimated glomerular filtration rate (eGFR) using bidirectional 2-sample Mendelian randomization (MR).

Methods: Single nucleotide polymorphisms associated with PUFAs and kidney function were obtained from the largest and most recent genome-wide association studies with sample sizes of 13,544, 13,506, 13,499, 13,527, and 13,549 for omega-3 fatty acids, omega-6 fatty acids, DHA, LA, and other PUFAs than 18:2 (otPUFA), and 480,698 and 1,201,909 for CKD and eGFR, respectively. MR inverse-variance weighted (IVW) and pleiotropy residual sum and outlier test (MR-PRESSO) were used for data analysis, supplemented with a weighted median estimator, MR-Egger regression, and multivariable MR, giving β or OR and their 95% CIs.

Results: There was suggestive evidence that higher omega-6 fatty acids were associated with increased eGFR using MR-PRESSO [β: 0.005 log(mL/min/1.73 m²) per SD increase in omega-6 fatty acids; 95% CI: 0.002, 0.008; P = 0.008]. Higher LA level was also associated with higher eGFR [β: 0.005 log(mL/min/1.73 m²) per SD increase in LA; 95% CI: 0.003, 0.007; P = 0.0007] using MR-PRESSO. Neither association of the other PUFAs, i.e., omega-3 fatty acids, DHA, and otPUFA, with CKD or eGFR nor the association of CKD and eGFR with PUFAs was found. Similar results were found in sensitivity analyses.

Conclusions: Our results suggest that higher omega-6 fatty acids and LA may increase eGFR levels. Although the estimated effects were relatively small, the results provide public health and research relevance, indicating the need for further longitudinal cohorts or randomized controlled trials on omega-6 fatty acids in improving kidney function.

Keywords: Mendelian randomization; chronic kidney disease; estimated glomerular filtration rate; omega-3; omega-6; polyunsaturated fatty acids.