The human response to acute enteral and parenteral phosphate loads

Abstract

The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; α-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads.

Keywords: FGF-23; Klotho; Vitamin D; intestinal; parathyroid hormone; phosphate; sensing.

Copyright © 2014 by the American Society of Nephrology.

Figures

Figure 1.

Intavenous and duodenal PO4 loading induce qualitatively similar effects on plasma PO4 and phosphrtropic hormones. (A–C) Effect of 36 hours of duodenal PO4 (1.53 mmol/kg body wt per 24 hours), of low-dose IV (1.15 mmol/kg body wt per 24 hours), and high-dose IV (2.30 mmol/kg body wt per 24 hours) loading on changes in plasma [PO4] and ionized [Ca], as well as changes in intact PTH) FGF-23, and 1,25(OH)2D. Filled symbols are the protocols using neutral sodium PO4, open symbols are the protocols using equimolar amounts of NaCl. ×P<0.05 for the comparison to own baseline; #P<0.05 for the comparison to the NaCl control.

Figure 2.

No difference in the urinary excretory pattern among the low-dose IV and duodenal PO4 loads. Time course of the increase in plasma [PO4] and the mean increase of urinary PO4 excretion per 2 hours during (0–36 hours) and after (36–72 hours) PO4 loading in the duodenal (upper panel) and low-dose IV group (lower panel). ×P<0.05 for the comparison to own baseline. UpV, denotes the amount in mmols of PO4 excreted during the colllection period.

Figure 3.

Timed renal PO4 excretion is similarly dependent on plasma [PO4] in duodenal, low and high dose intravenous groups. (A–D) Relationships of the individual changes in urinary PO4 excretion per 2 hours on the corresponding changes in plasma [PO4] in all experimental groups. Time points are 2, 4, 8, and 12 hours after the beginning of PO4 loading. UpV, denotes the amount in mmols of PO4 excreted in urine for the given plasma [PO4].

Figure 4.

Fractional renal phosphate clearance progressively increases during constant PO4 loading in all three groups. Renal fractional PO4 clearance (per 100 ml GFR) during (0–36 hours) and after (36–72 hours) PO4 loading in all three experimental groups. *P<0.05 for comparison to own baseline.

Figure 5.

Intestinal PO4 absorption is 73%, while the administered PO4 load are exclusively eliminated by the kidney. Comparison of the cumulative urinary PO4 excretion with infused amounts of PO4 in the duodenal (left two bars) and the mean of both IV (right two bars) infusion groups. Observations were carried for 120 hours after beginning of PO4 loading.