Observational or Genetically Predicted Higher Vegetable Intake and Kidney Function Impairment: An Integrated Population-Scale Cross-Sectional Analysis and Mendelian Randomization Study

Background: Further exploration of the possible effects of vegetable intake on kidney function is warranted. Objective: We aimed to study the causality of the association between vegetable intake and kidney function by implementing Mendelian randomization (MR) analysis. Methods: This study comprised a cross-sectional dietary investigation using UK Biobank data and MR analysis. For the cross-sectional investigation, 432,732 participants aged 40-69 y from the UK Biobank cohort were included. Self-reported vegetable intake was the exposure, and the outcomes were the estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). Next, we included 337,138 participants of white British ancestry in the UK Biobank, and a genome-wide association study (GWAS) was performed to generate a genetic instrument. For MR, we first performed polygenic score (PGS)-based 1-sample MR. In addition, 2-sample MR was performed with CKDGen GWAS for kidney function traits, and the inverse variance weighted method was the main MR method. Results: Higher vegetable intake was cross-sectionally associated with a higher eGFR (per heaped tablespoon increase; beta: 0.154; 95% CI: 0.144, 0.165) and lower odds of CKD (OR: 0.975; 95% CI: 0.968, 0.982). A PGS for vegetable intake was significantly associated with a higher eGFR [per ordinal category increase (0, 1-3, 4-6, >= 7 tablespoons per day); beta: 4.435; 95% CI: 2.337, 6.533], but the association with CKD remained nonsignificant (OR: 0.468; 95% CI: 0.143, 1.535). In the 2-sample MR, the causal estimates indicated that a higher genetically predicted vegetable intake was associated with a higher eGFR (percent change; beta: 3.071; 95% CI: 0.602, 0.560) but nonsignificantly associated with the risk of CKD (OR: 0.560; 95% CI: 0.289, 1.083) in the European ancestry data from the CKDGen. Conclusions: This study suggests that higher vegetable intake may have a causal effect on higher eGFRs in the European population.

Automated summary

Higher vegetable intake is associated with higher eGFR and lower odds of CKD in a cross-sectional investigation, and genetically predicted vegetable intake is causally associated with higher eGFR in European populations. However, the association with CKD remains inconclusive.