ADAPTATION TO CHANGES IN DIETARY PHOSPHORUS INTAKE IN HEALTH AND IN RENAL-FAILURE

Phosphate (P-i) homeostasis is maintained by the ability of the kidney s to adjust the tubular reabsorption of P-i to changes in the dietary intake of phosphorus. Renal tubular P-i reabsorption increases with th e ingestion of a low-phosphorus diet (LPD) and decreases when a high-p hosphorus diet (HPD) is consumed. A similar adaptive mechanism is also operative at the intestinal microvillus. The adaptive changes in P-i reabsorption are independent of parathyroid hormone production and are paralleled by similar changes in the NA(+)-dependent P-i transport at the brush border membrane (BBM). Type II Na+-P-i cotransporters (NaPi -2) are mainly involved in such regulatory mechanisms. Chronic dietary phosphorus restriction leads to Increased Na+-P-i cotransport rate, a long with increased NaPi-2 protein and mRNA abundance. in acute dietar y phosphorus restriction, transport rate and NaPi-2 protein are also i ncreased, but mRNA abundance remains unchanged. A shuttling mechanism involving translocation of cotransporters from intracellular pools to the BBM is involved in the rapid proximal tubular adaptation. The inte stinal adaptation to changes in dietary phosphorus ape similar to thos e described for the renal P-i transport, but the molecular structure o f the intestinal Na+-P-i cotransporter is not known. When nephron mass is reduced, phosphate homeostasis is maintained through enhanced P-i excretion by residual nephrons. The adaptation to renal mass reduction is mediated by increased parathyroid hormone (PTH) production and by PTH-Independent mechanisms, including increased intrarenal dopamine pr oduction. The adaptive changes of P-i transport to dietary phosphorus restriction can counteract the effect of dietary phosphorus reduction often prescribed in patients with renal failure. However, because of t he reduced filtered load of P-i, the overall impact on serum P-i conce ntration is minimal.