Renal adaptation to phosphorus deprivation: Characterization of early events

Abstract

Renal adaptation to low dietary phosphorus (P) can occur within 4 h. To characterize events preceding adaptation, rats were gavaged with 0.6% P (+P) or 0.03% P (-P) diet and killed 1, 2, or 4 h later. Brush border membrane vesicles were prepared and Na-dependent phosphate (Pi), glucose, and 1-proline transport were measured. In intact rats, 1 h after gavage, serum P in +P was 8.0 +/- 0.5 and in -P, 6.1 +/- 0.4 mg/dl, p less than 0.01. One and 2 h after gavage, Pi uptake was similar between groups; at 4 h, 0.25 min Pi uptake was increased by 59.3% +/- 14.8 in -P, p less than 0.02, n = 11. In thyroparathyroidectomized rats, Pi uptake increased in -P by 40.1% +/- 7.4 compared to +P at 2.5 h after gavage, and by 51.3 +/- 9.3 at 4 h, p less than 0.025, n = 11. When actinomycin D or cycloheximide were administered both 16 h prior to and at gavage, 0.25 min Pi uptake 4 h after gavage was 59.1% +/- 14 and 60.6% +/- 19 higher in -P than +P, respectively, p less than 0.025. The adaptation was detected only when measured with an inward-directed Na-gradient. Na-dependent glucose and proline uptakes were not changed by -P diet. These studies demonstrate that early renal adaptation to low dietary P is preceded by a fall in serum P, is independent of parathyroid hormone, and does not require protein synthesis. Early adaptation may represent an increased rate of carrier movement or a change in availability of already synthesized carrier. The signal for adaptation may be the decrease in serum P, or filtered load of phosphorus.

Regulation of phosphate transport in proximal tubules

“…The rapid increase of brush border Na + /P i cotransport was not blocked by cycloheximide, which suggests that de novo synthesis of Na + /P i cotransporters might not be necessary [73]. Yet, so far, there is no clear evidence for the existence of an intracellular, subapical pool of Na + /P i cotransporters that could explain the rapid adaptive phenomenon.…”

“…Interestingly, the capacity of renal P i reabsorption adapts to altered intake of P i within less than an hour (acute adaptation) and remains adjusted during prolonged intake of dietary P i (chronic adaptation) [71,73].…”

“…Within the first four hours after ingestion of a low P i diet, brush border Na + /P i cotransport increases due to an increase of the amount of NaPi-lla [26,71,73]. Rapid upregulation induced by low P i diet was also observed for Pit-2 but not for NaPi-llc [79 and Ravera S et al, unpublished observations].…”

“…Yet, so far, there is no clear evidence for the existence of an intracellular, subapical pool of Na + /P i cotransporters that could explain the rapid adaptive phenomenon. Based on the observation that the fall in the serum level of P i after ingestion of a low P i diet precedes up-regulation of Na/Pi cotransport [73], one might hypothesize the existence of one or more sensing mechanism(s) for P i that eventually may be located in the proximal tubular cells.…”

Clinical Disorders of Phosphate Homeostasis

“…However, studies indicate that hypophosphatemia is a relatively frequent occurrence in children under 5 years of age presenting with kwashiorkor or marasmic kwashiorkor [215]. With a decline in ingested phosphate, the renal TmP increases and urinary phosphate excretion decreases [216]. In addition, gastrointestinal phosphate secretion gradually lessens.…”