Early-life overconsumption of a high-carbohydrate diet induces metaflammation and kidney injury without impairment of function in adult Wistar rats.

Frequent consumption of sugary and calorie-dense foods and beverages during childhood may contribute to the development of metabolic syndrome (MetS) in adulthood, a risk that can manifest independently of overweight status. Metaflammation, a low-grade inflammation associated with MetS, can induce functional loss in multiple tissues, including the kidneys, potentially signaling the onset of damage. This work aimed to evaluate the progressive structural changes, damage, and kidney function associated with metaflammation-induced MetS in young to adult Wistar rats. Early-life rats were divided into two groups: one fed a standard diet and the other a high-carbohydrate diet (HCD). Three analysis time points were designed: 6 weeks (adolescence), 12 weeks (young adulthood), and 20 weeks (adults). Zoometry, nutritional status, metabolic biomarkers, kidney function, serum and urinary cytokines, and kidney injury molecule 1 (KIM-1) were measured in each cohort. Histopathologic modifications, inflammation, and redox balance were analyzed in the renal cortex. Results show that HCD consumption progressively induces MetS and metaflammation, increasing serum levels of inflammatory cytokines and KIM-1. However, renal function was not affected. Renal cortex inflammation began in adolescence, even before oxidative stress was established in young and adult rats. The renal tissue showed hallmarks of early kidney damage, including mesangial cell expansion, podocyte loss, hypertrophy, tubular hyperplasia, and fibrosis. In urine, levels of KIM-1, TGF-β, and IL-1β increased. In conclusion, chronic HCD consumption from early life establishes MetS and metaflammation, leading to silent nephropathy. This state is characterized by structural remodeling and profibrotic signaling that occur independently of standard clinical kidney function markers in Wistar rats.