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J Am Soc Nephrol. 2014 Dec;25(12):2730-9. doi: 10.1681/ASN.2013101076. Epub 2014 May 22.

The human response to acute enteral and parenteral phosphate loads.

Author information

1
Medizinische Universitätsklinik, Kantonsspital Bruderholz, University of Basel, Basel, Switzerland; and.
2
Department of Medicine, University of California, San Francisco, San Francisco, California.
3
Medizinische Universitätsklinik, Kantonsspital Bruderholz, University of Basel, Basel, Switzerland; and reto.krapf@hirslanden.ch.

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

PMID:
24854273
PMCID:
PMC4243350
DOI:
10.1681/ASN.2013101076
[Indexed for MEDLINE]
Free PMC Article

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