The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.

The effect of orally administering cabbage juice on tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) productivity was studied in resident peritoneal macrophages from normal and hepatoma-bearing rats. The productivity of TNF and IL-1 was stimulated by gastric intubation of cabbage juice in the normal state, but not in the hepatoma-bearing state where the production of these cytokines had already been stimulated. From these results, cabbage may contain some effective component(s) that can be absorbed from the gastrointestinal tract to stimulate the production of TNF and IL-1.