Certain Foods May Help Reduce Risk of IgA Nephropathy, Study Finds

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Findings from a recent study suggest certain dietary exposures may have a protective effect against IgA nephropathy (IgAN).¹

Results of the 2-sample Mendelian randomization (MR) analysis showed alcohol intake frequency was associated with a significantly increased risk of IgAN, suggesting that reducing alcohol intake may be an important protective strategy against IgAN. Additionally, cheese, cereal, and sushi intake were all associated with a decreased risk of IgAN.¹

“The drug treatment of IgAN relies on renin-angiotensin-aldosterone system inhibitors, glucocorticoids and immunosuppressants. However, some patients experience severe adverse drug reactions and poor sensitivity, which makes IgAN treatment challenging,” Longyang Jiang, PhD, a professor at the Affiliated Hospital of Southwest Medical University in China, and colleagues wrote.¹ “Therefore, it is necessary to conduct a comprehensive search for risk factors related to IgAN and to provide recommendations for the prevention of IgAN.”

A leading cause of glomerulonephritis and renal failure, IgAN is characterized by the deposition of IgA in the glomerular basement membrane. The lack of understanding of its pathogenesis often limits risk stratification and effective treatment.²

Although findings from previous observational studies have suggested dietary intake may play an important role in IgAN development, investigators pointed out these studies cannot efficiently exclude the possibility of reverse causality and confounding factors. To clarify these findings and further evaluate causal associations between diet and IgAN, investigators conducted a 2-sample MR analysis using exposure data from the UK Biobank.¹

The exposures were categorized as protein, carbohydrates, plant-based diets, and beverages. A total of 26 dietary exposures were assessed, and outcome data for IgAN (n = 477,784, including n_case = 15,587 and n_control = 462,197) were extracted from the EBI database.¹

Investigators noted the instrumental variables (IVs) selected for the study satisfied 3 assumptions: the IVs were strongly related to dietary intake; the IVs were unrelated to any confounding factors; and the IVs had no direct correlation with IgAN via factors other than dietary intake. They chose the inverse variance weighted (IVW) method as the primary approach to assess the causal relationship between dietary intake and IgAN, additionally using MR–Egger regression, weighted median, simple mode, and weighted mode as complements to the IVW.¹

The primary results of the IVW analysis showed alcohol intake frequency (odds ratio [OR], 1.267; 95% CI, 1.100 to 1.460; P = .0010295) was a risk factor for IgAN. Investigators pointed out cheese intake (OR, 0.626; 95% CI, 0.492 to 0.798; P = .0001559), cereal intake (OR, 0.652; 95% CI, 0.439 to 0.967; P = .0334126), and sushi intake (OR, 0.145; 95% CI, 0.021 to 0.997; P = .049685) were protective factors against IgAN, while the rest of the dietary intakes were not significantly related to the occurrence of IgAN (IVW P > 0.05).¹

Similar results for alcohol intake frequency (IVW beta, 0.236969; P = .0010295) were obtained through the MR–Egger regression (beta, 0.0060511; OR, 1.006; 95% CI, 0.729 to 1.389; P = .9707445), weighted median (beta, 0.1855399; OR, 1.204; 95% CI, 0.980 to 1.478; P = .076532), simple mode (beta, 0.4519185; OR, 1.571; 95% CI, 0.961 to 2.570; P = 0.0757164), and weighted mode (beta, 0.1314467; OR, 1.140; 95% CI, 0.872 to 1.492; P = .340832).¹

For cheese intake (IVW beta, −0.4677279; P = .0001559), investigators again observed similar trends in MR–Egger regression (beta, −1.0076467; OR, 1.006; 95% CI, 0.729 to 1.389; P = .9707445), weighted median (beta, −0.4766256; OR, 1.204; 95% CI, 0.980–1.478; P = .076532), simple mode (beta, −0.4767936; OR, 1.571; 95% CI, 0.961–2.570; P = .0757164), and weighted mode (beta, −0.4767936; OR, 1.140; 95% CI, 0.872–1.492; P = .340832). Additionally, for cereal intake (IVW beta, −0.4279035; P = .0334126) and sushi intake (IVW beta, −1.92976; P = .049685), the MR-Egger, weighted median, simple mode, and weighted mode analyses also showed consistency.¹

Investigators noted the P values of Cochran’s Q for cheese, cereal, and sushi intakes were all > 0.05, indicating no heterogeneity, and there was no evidence of pleiotropy according to the MR-Egger intercept (P >.05). For alcohol intake frequency, pleiotropy was detected using the MR-PRESSO global test (P = .047), but the outlier test did not detect any significant outliers and the leave-one-out method indicated that the results were unaffected after removing each SNP. Investigators also pointed out the results of sensitivity analysis indicated tat the MR analysis results were reliable.¹

They acknowledged multiple limitations to these findings, including the overrepresentation of European participants and potential lack of generalizability to non-European populations; the inability to evaluate the nonlinear association between the exposures and the risk of IgAN; the lack of assessment of other dietary factors; and the need for further validation through additional GWAS data.¹

“To the best of our knowledge, this is the first study using the MR method to explore the causal association between dietary intake and risk of IgAN,” investigators concluded.¹ “The results indicated that alcohol intake frequency was associated with a higher risk of IgAN, whereas cheese, cereal, and sushi intake were associated with a lower risk of IgAN.”

References

1. ^{Li Y, Wan S, Liu J, et al. Causal relationship between dietary intake and IgA nephropathy: a Mendelian randomization study. Frontiers. https://doi.org/10.3389/fnut.2024.1400907}
2. ^{Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. April 22, 2024. Accessed September 27, 2024. https://www.ncbi.nlm.nih.gov/books/NBK538214/}