The Western diet is rich in fat, calories, and phosphate. Excessive fat and calorie intake have adverse effects on health. But the potential harms of excessive phosphate intake are barely known. A recent study describes how dietary phosphate injures the kidney. 

When phosphate intake increases relative to the number of functioning nephrons, circulating levels of FGF23 (a hormone that increases the excretion of phosphate per nephron) also increase to maintain phosphate homeostasis. FGF23 suppresses phosphate reabsorption in renal tubules, ultimately increasing the phosphate concentration in the tubule fluid. On exceeding a threshold, microscopic particles containing calcium phosphate crystals appear in the tubule lumen, which damages tubule cells by binding to the TLR4 expressed on them. Persistent tubule damage generates interstitial fibrosis, reduces the number of nephrons, and further boosts FGF23 to trigger a degenerative spiral causing progressive nephron loss. 

Chronic kidney disease (CKD) progression occurs when serum FGF23 levels exceed 53 pg/mL in humans. 

This study determines calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during aging and CKD progression.

J Clin Invest. 2021 Aug 16;131(16):e145693. doi: 10.1172/JCI145693. PMID: 34185705; PMCID: PMC8363285.