Histopathology And Urinary Metabonomics Reveal The Role Of Dietary Salt On The Pathogenesis Of Fructose-Induced Kidney Injury

Although increasing evidence demonstrates that dietary salt is involved in hypertension induced by high fructose levels (HF), it is not known how dietary salt plays a role in kidney injury caused by HF. Therefore, we investigated the effects of different diets on abnormal renal histology and urinary metabolites. SD rats were randomly divided into five groups: a normal diet (0.5% NaCl, w/w); a high-salt diet (HS; 8% NaCl); 10% fructose in water (HF; w/v); high-salt diet and 10% fructose water (HF-HS); and low-salt diet (LS; 0.07% NaCl) with 10% fructose water (HF-LS). Eight weeks of the HF diet induced marked glomerular hypertrophy (PAS-staining), podocyte injury (desmin), tubular damage and inflammatory cell infiltration. However, the HS diet produced glomerular sclerosis (alpha-SMA) and podocyte injury. Importantly, metabonomic analysis showed that compared with the normal diet, the HS diet elicited the urinary excretion of trimetlylamine oxide (TMAO) and hippurate (urinary microbial cometabolites), whereas high fructose primarily affected the activity of the tricaboxylic acid (TCA) cycle. Notably, switching to LS diet halted the progression of HF-induced renal injuries. Further, the excretion of TMAO and hippurate from HF-LS rats was significantly reduced compared with normal rats, whereas the HF+HS diet promoted excretion. Our findings indicate that dietary salt is involved in renal injury induced by HF, probably by affecting gut microbiota activity.