Genetically predicted dietary diversity protects against renal failure while extreme carbohydrate restriction increases the risk in a Mendelian randomization study

The causal relationship between strict dietary patterns and nonspecific renal failure (RF) remains a subject of intense clinical debate. Epidemiological observations are frequently confounded by post-diagnostic health-seeking behaviors and metabolic comorbidities. This study aimed to investigate the genetically predicted causal impacts of both dietary diversity (unrestricted eating) and specific carbohydrate-restricted diets (avoidance of sugar and wheat) on the risk of RF. Summary-level genome-wide association study data were leveraged. We first conducted univariable Mendelian randomization (MR) to evaluate the overall causal effect of a comprehensive dietary pattern (“Eat all” encompassing eggs, dairy, wheat, and sugar). Subsequently, multivariable MR was employed to disentangle the independent effects of individual dietary exclusions, mutually adjusting for genetic liabilities of overlapping eating habits. Instrument strength was verified using F -statistics. MR results were expressed as odds ratios with 95% confidence intervals. In univariable MR, a genetically predicted balanced dietary pattern (“Eat all”) demonstrated a profound, highly significant causal protective effect against RF (Inverse variance-weighted: Beta = −2.064, standard error (SE) = 0.615, P  = .00079) (odds ratios = 0.1269; 95% confidence intervals: 0.038–0.424). Conversely, in the multivariable MR model conditioning on overlapping dietary avoidances, specific carbohydrate restrictions emerged as independent hazards; “never eat sugar” (Estimate = 0.624, SE = 0.277, P  = .026) and “never eat wheat” (Estimate = 2.292, SE = 1.094, P  = .038) were both independently associated with an elevated susceptibility to RF. Restrictions on eggs and dairy products showed no significant independent effects. Genetically predicted dietary diversity exerts a robust renoprotective effect, whereas the extreme exclusion of primary carbohydrate sources (sugar and wheat) independently drives RF risk. These findings suggest that long-term restriction of key macro-nutritional vectors may disturb renal metabolic homeostasis, underlining the need for caution before adopting untargeted elimination diets.