Abstract
Polyunsaturated fatty acid (PUFA) intake is generally associated with better renal function, while the association of monounsaturated fatty acids (MUFAs) remains unconfirmed. Mendelian randomization (MR) analysis was used to obtain unconfounded estimates of the causal association of dietary intake and genetically determined serum PUFA and MUFA levels with measures of renal function. Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were used. Data from the largest genome-wide association studies (GWAS) on MUFAs, PUFAs, eGFR, and chronic kidney disease (CKD) were analysed for the entire sample. A total of 16,025 participants were included. eGFR improved across increasing quartiles of total PUFA intake from 86.3 ± 0.5 (Q1) to 96.2 ± 0.5 mL/min/1.73 m² (Q4), (p < 0.001). Conversely, there was no association between MUFA intake and measures of renal function (all p > 0.21). In multivariable models, the top quartile of PUFA intake had a 21% lower risk for CKD, but there was no significant association between CKD risk and MUFA intake. Genetically determined serum MUFA (heptadecenoate (17:1), myristoleic acid (14:1), and palmitoleic acid (16:1)) and PUFA (α-linolenic acid and eicosapentaenoic acid) concentrations had no significant association with eGFR and CKD risk. Additionally, no association was found in the analyses stratified by diabetes status. Higher dietary PUFA intake is associated with lower risk of CKD, while there was no association with serum levels of MUFAs or PUFAs. Additional studies including clinical trials are warranted.
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Key Points
Mendelian randomization (MR) analysis using functional single nucleotide polymorphisms (SNPs) associated with specific changes in physiological exposures (such as serum MUFAs and PUFAs) as genetic instruments of analysis are capable of providing unbiased and robust evidence on the mechanisms of the pathogenesis of disease and the efficacy of treatments. Compared with conventional risk-factor epidemiology, these studies are considerably less prone to confounding, residual bias, and reverse causation. While randomized controlled trials (RCTs) are considered useful for the determination of causality, they are often limited by cost, time, and ethical constraints, depending on the characteristics of the exposure and disease state being studied. MR studies can be considered a way to avoid these inherent issues with RCTs and, in addition to this, the data from such studies can be used to improve the development of pilot RCTs and strategies for clinical trials by elucidating the potential efficacy of an intervention or even the magnitude of effect in selected individuals and groups.
Therefore, national survey data (Nutrition and Health Examination Surveys (NHANES)) and Mendelian randomization (MR) analysis were used to determine unbiased estimates of the casual association of genetically determined serum levels and dietary intake of MUFAs and PUFAs with renal function.
e analyzed dietary data on MUFAs and PUFAs intake, along with a set of genetic variants that have been demonstrated to be associated with four circulating serum MUFAs and PUFAs in order to determine their association with renal function. No significant association was observed between different dietary intakes of MUFAs. Conversely, the dietary intake of PUFAs was inversely associated with measures of kidney function and prevalent CKD. However, MR analyses did not support any causal effect of various MUFA or PUFA concentrations on CKD. The MR analysis also showed no such association between genetically determined markers of serum ALA and EPA and renal function. This could potentially indicate that the results of the observational study of dietary intake could be affected by confounding or even reverse causation. Briefly, healthy dietary choices (such as increased PUFA intake) often occur together with other healthy dietary or lifestyle factors. In conclusion, no evidence to support an association between the intake of total or individual MUFAs, nor a causal effect of serum MUFAs on CKD was found. While no causal effect of genetically determined serum PUFAs on prevalent CKD could be determined, a clear inverse association was observed between the dietary intake of PUFAs and CKD. While further investigation is required into the role of PUFAs in the development of CKD, these findings do not contradict the current evidence-base for the benefit of replacing dietary SFAs with MUFAs and, preferentially, PUFAs.