RESUMEN
Vascular calcification progresses under hyperphosphatemia, and represents a risk factor for cardiovascular disease in chronic kidney disease (CKD) patients. We recently indicated that phosphorus (P) fluctuations also exacerbated vascular calcification in early-stage CKD rats. Dietary fiber intake is reportedly associated with cardiovascular risk. This study investigated the effects of dietary fiber on vascular calcification by repeated P fluctuations in early-stage CKD rats. Unilateral nephrectomy rats were used as an early-stage CKD model. For 36 days, a P fluctuation (LH) group was fed low-P (0.02% P) and high-P (1.2% P) diets alternating every 2 days, and a P fluctuation with dietary fiber intake (LH + F) group was fed low-P and high-P diets containing dietary fiber alternating every 2 days. The effect on vascular calcification was measured calcium content. Effects on uremic toxin were measured levels of indoxyl sulfate (IS) and investigated gut microbiota. The LH + F group showed significantly reduced vessel calcium content compared to the LH group. Further, dietary fiber inhibited increases in blood levels of IS after intake of high-P diet, and decreased uremic toxin-producing intestinal bacteria. Dietary fiber may help suppress progression of vascular calcification due to repeated P fluctuations in early-stage CKD rats by decreasing uremic toxin-producing intestinal bacteria.
RESUMEN
Cardiovascular disease is a major cause of death among hemodialysis patients. Hyperphosphatemia induces cardiovascular disease through vascular endothelial dysfunction and calcification. Repetition of a short-term excessive-phosphorus (P) diet causes transient elevations in plasma P and subsequent vascular endothelial dysfunction in normal rats. The purpose of this study was to investigate the effects of the P fluctuation on vascular calcification and inflammation in rats after unilateral nephrectomy as an early-stage chronic kidney disease (CKD) model. Rats were bred for 36 days; CP group, fed a control P (0.6%) diet; HP group, fed a high-P (1.2%) diet; and P fluctuation group, fed low-P (0.02%) and high-P diets alternately every 2 days. Influences on vascular calcification were analyzed using Von Kossa staining and measurement of vessel Ca content. The influence on inflammation was measured as urinary levels of 8-hydroxy-2'-deoxyguanosine. We demonstrated that the P fluctuation group showed similar vascular calcification and inflammation to the HP group, despite having the same total P intake as the CP group. A diet avoiding P fluctuations may be important for patients with early-stage CKD.