Adaptation to changes in dietary phosphorus intake in health and in renal failure

Abstract

Phosphate (Pi) homeostasis is maintained by the ability of the kidneys to adjust the tubular reabsorption of Pi to changes in the dietary intake of phosphorus. Renal tubular Pi reabsorption increases with the ingestion of a low-phosphorus diet (LPD) and decreases when a high-phosphorus diet (HPD) is consumed. A similar adaptive mechanism is also operative at the intestinal microvillus. The adaptive changes in Pi reabsorption are independent of parathyroid hormone production and are paralleled by similar changes in the Na+-dependent Pi transport at the brush border membrane (BBM). Type II Na+-Pi cotransporters (NaPi-2) are mainly involved in such regulatory mechanisms. Chronic dietary phosphorus restriction leads to increased Na+-Pi cotransport rate, along with increased NaPi-2 protein and mRNA abundance. In acute dietary phosphorus restriction, transport rate and NaPi-2 protein are also increased, 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 intestinal adaptation to changes in dietary phosphorus are similar to those described for the renal Pi transport, but the molecular structure of the intestinal Na+-Pi cotransporter is not known. When nephron mass is reduced, phosphate homeostasis is maintained through enhanced Pi 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 production. The adaptive changes of Pi transport to dietary phosphorus restriction can counteract the effect of dietary phosphorus reduction often prescribed in patients with renal failure. However, because of the reduced filtered load of Pi, the overall impact on serum Pi concentration is minimal.